Cathy is a member of the Biology and Biotechnology discipline in the School of Life Sciences. Cathy's research interest in neuroscience, in particular in neurotrauma (brain and spinal cord injury). She has conducted studies on human autopsy material and uses animal models to investigate damage and repair of the central nervous system.
She completed her PhD in 2006 (UNSW), and joined UTS in 2011 teaching Biomedical Science. Her fields of expertise are in Histology and Immunohoistochemistry. She has established sucessful research collaborations with academics from Australian and overseas universities and is currently investigating the role of endogenous neural progenitor cells (stem cells) in spinal cord tissue and how spinal cord injury in the young differs from adult injury.
Society for Neuroscience (SfN)
Australasian Neuroscience Society
Stem Cell Network NSW
Spinal Cord Injury Network
Can supervise: YES
An examination of the cellular and inflammatory response in rats after spinal cord injury, and the effects of age, location and survival time (UTS Center for Health Technologies)
Modulation of connexin43 hemichannels in reducing secondary spinal cord injuries (Spinal Cord Injury Network & New Zealand Neurological Foundation with the Catwalk Trust)
Endogenous neural progenitor cell responses following spinal cord (Early Career Research Grant, UTS)
Age related cytoskeletal pathology in human brain from Sri Lanka: A correlation of morphological and molecular genetic study
Spinal cord loading conditions in young and adult spinal cord injuries (SpinalCare)
Bachelor of Biomedical Science - Program Director
Histology - Subject co-ordinator
Haematology - Lecturer
Anatomical Pathology - Lecturer
Transfusion Science - Lecturer
Neuroscience - Lecturer - Lecturer
Human Pathophysiology - Lecturer
Pelegri, NG, Gorrie, CA & Santos, J 2019, 'Rat Hippocampal Neural Stem Cell Modulation Using PDGF, VEGF, PDGF/VEGF, and BDNF.', Stem Cells International, vol. 2019, p. 4978917.View/Download from: UTS OPUS or Publisher's site
Neural stem cells have become the focus of many studies as they have the potential to differentiate into all three neural lineages. This may be utilised to develop new and novel ways to treat neurological conditions such as spinal cord and brain injuries, especially if the stem cells can be modulated in vivo without additional invasive surgical procedures. This research is aimed at investigating the effects of the growth factors vascular endothelial growth factor, platelet-derived growth factor, brain-derived neurotrophic factor, and vascular endothelial growth factor/platelet-derived growth factor on hippocampal-derived neural stem cells. Cell growth and differentiation were assessed using immunohistochemistry and glutaminase enzyme assay. Cells were cultured for 14 days and treated with different growth factors at two different concentrations 20 ng/mL and 100 ng/mL. At 2 weeks, cells were fixed, and immunohistochemistry was conducted to determine cellular differentiation using antibodies against GFAP, nestin, OSP, and NF200. The cell medium supernatant was also collected during treatment to determine glutaminase levels secreted by the cells as an indicator of neural differentiation. VEGF/PDGF at 100 ng/mL had the greatest influence on cellular proliferation of HNSC, which also stained positively for nestin, OSP, and NF200. In comparison, HNSC in other treatments had poorer cell health and adhesion. HNSC in all treatment groups displayed some differentiation markers and morphology, but this is most significant in the 100 ng/ml VEGF/PDGF treatment. VEGF/PDGF combination produced the optimal effect on the HNSCs inducing the differentiation pathway exhibiting oligodendrocytic and neuronal markers. This is a promising finding that should be further investigated in the brain and spinal cord injury.
Tonkin, RS, Bowles, C, Perera, CJ, Keating, BA, Makker, PGS, Duffy, SS, Lees, JG, Tran, C, Don, AS, Fath, T, Liu, L, O'Carroll, SJ, Nicholson, LFB, Green, CR, Gorrie, C & Moalem-Taylor, G 2018, 'Attenuation of mechanical pain hypersensitivity by treatment with Peptide5, a connexin-43 mimetic peptide, involves inhibition of NLRP3 inflammasome in nerve-injured mice.', Experimental neurology, vol. 300, pp. 1-12.View/Download from: UTS OPUS or Publisher's site
Connexin43 (Cx43) hemichannels in spinal cord astrocytes are implicated in the maintenance of neuropathic pain following peripheral nerve injury. Peptide5 is a Cx43 mimetic peptide that blocks hemichannels. In this study, we investigated the effects of spinal delivery of Peptide5 on mechanical pain hypersensitivity in two mouse models of neuropathic pain, peripheral nerve injury and chemotherapy-induced peripheral neuropathy (CIPN). We demonstrated that 10days following a chronic constriction injury (CCI) of the sciatic nerve, Cx43 expression, co-localised predominantly with astrocytes, was increased in the ipsilateral L3-L5 lumbar spinal cord. An intrathecal injection of Peptide5 into nerve-injured mice, on day 10 when pain was well-established, caused significant improvement in mechanical pain hypersensitivity 8h after injection. Peptide5 treatment resulted in significantly reduced Cx43, and microglial and astrocyte activity in the dorsal horn of the spinal cord, as compared to control saline-treated CCI mice. Further in vitro investigations on primary astrocyte cultures showed that 1h pre-treatment with Peptide5 significantly reduced adenosine triphosphate (ATP) release in response to extracellular calcium depletion. Since ATP is a known activator of the NOD-like receptor protein 3 (NLRP3) inflammasome complex, a key mediator of neuroinflammation, we examined the effects of Peptide5 treatment on NLRP3 inflammasome expression. We found that NLRP3, its adaptor apoptosis-associated spec-like protein (ASC) and caspase-1 protein were increased in the ipsilateral spinal cord of CCI mice and reduced to naïve levels following Peptide5 treatment. In the models of oxaliplatin- and paclitaxel-induced peripheral neuropathy, treatment with Peptide5 had no effect on mechanical pain hypersensitivity. Interestingly, in these CIPN models, although spinal Cx43 expression was significantly increased at day 13 following chemotherapy, NLRP3 expression was not altered. These result...
Nguyen, T, Li, GE, Chen, H, Cranfield, CG, McGrath, KC & Gorrie, CA 2018, 'Maternal E-Cigarette Exposure Results in Cognitive and Epigenetic Alterations in Offspring in a Mouse Model.', Chemical research in toxicology, vol. 31, no. 7, pp. 601-611.View/Download from: UTS OPUS or Publisher's site
Electronic cigarette (e-cigarette) use is on the rise worldwide and is particularly attractive to young people and as a smoking substitute by pregnant woman. There is a perception in pregnant women and women of child-bearing age that the use of e-cigarettes (vaping) is safer than smoking tobacco cigarettes during pregnancy. However, there is little evidence to support this perception. Here, we examined the offspring from mouse dams that had been exposed during and after pregnancy to ambient air (sham) ( n = 8), e-cigarette aerosols with nicotine ( n = 8), or e-cigarette aerosols without nicotine ( n = 8). Offspring underwent cognitive testing at 12 weeks of age and epigenetic testing of brain tissues at 1 day, 20 days, and 13 weeks after birth. The findings showed deficits in short-term memory, reduced anxiety, and hyperactivity in offspring following maternal e-cigarette exposure using the novel object recognition and elevated plus maze tests. In addition, global DNA methylation was increased in the brains of offspring soon after birth. Using a quantitative-PCR array specific to chromatin modification enzymes on genomic DNA and histones,13 key genes were identified to be significantly altered in the offspring brains from the e-cigarette groups compared to the nonexposed groups. The changes to genes Aurka, Aurkb, Aurkc, Kdm5c, Kdm6b, Dnmt3a, Dnmt3b, and Atf2, all associated with modulating neurological activity, were validated using RT-qPCR. In conclusion, in a mouse model, maternal exposure to e-cigarette aerosols resulted in both cognitive and epigenetic changes in offspring. This suggests that the use of e-cigarettes during pregnancy may have hitherto undetected neurological consequences on newborns.
Chen, H, Chan, YL, Linnane, C, Mao, Y, Anwer, AG, Sapkota, A, Annissa, TF, Herok, G, Vissel, B, Oliver, BG, Saad, S & Gorrie, CA 2018, 'L-Carnitine and extendin-4 improve outcomes following moderate brain contusion injury.', Scientific reports, vol. 8, no. 1.View/Download from: UTS OPUS or Publisher's site
There is a need for pharmaceutical agents that can reduce neuronal loss and improve functional deficits following traumatic brain injury (TBI). Previous research suggests that oxidative stress and mitochondrial dysfunction play a major role in neuronal damage after TBI. Therefore, this study aimed to investigate two drugs known to have antioxidant effects, L-carnitine and exendin-4, in rats with moderate contusive TBI. L-carnitine (1.5 mM in drinking water) or exendin-4 (15 µg/kg/day, ip) were given immediately after the injury for 2 weeks. Neurological function and brain histology were examined (24 h and 6 weeks post injury). The rats with TBI showed slight sensory, motor and memory functional deficits at 24 h, but recovered by 6 weeks. Both treatments improved sensory and motor functions at 24 h, while only exendin-4 improved memory. Both treatments reduced cortical contusion at 24 h and 6 weeks, however neither affected gliosis and inflammatory cell activation. Oxidative stress was alleviated and mitochondrial reactive oxygen species was reduced by both treatments, however only mitochondrial functional marker protein transporter translocase of outer membrane 20 was increased at 24 h post injury. In conclusion, L-carnitine and exendin-4 treatments immediately after TBI can improve neurological functional outcome and tissue integrity by reducing oxidative stress.
Mao, Y, Tonkin, RS, Nguyen, T, O'Carroll, SJ, Nicholson, LF, Green, CR, Moalem-Taylor, G & Gorrie, CA 2017, 'Systemic administration of Connexin43 mimetic peptide improves functional recovery following traumatic spinal cord injury in adult rats.', Journal of Neurotrauma, vol. 34, no. 3, pp. 707-719.View/Download from: UTS OPUS or Publisher's site
Blocking of Connexin43 hemichannels, the main gap junction protein located on astrocytes in the central nervous system, has been shown to reduce neural injury in a number of models. We previously demonstrated that local administration of a Connexin43 mimetic peptide, Peptide5, reduces secondary tissue damage after spinal cord injury (SCI). Here, we investigated whether acute systemic delivery of Peptide5 is also protective in a model of SCI. Rats were subjected to a mild spinal cord contusion using the MASCIS impactor and were injected intraperitoneally with Peptide5 or a scrambled peptide immediately and at 2 and 4 hours post-injury. Rats were tested for locomotor recovery and pain hypersensitivity and euthanised at 8 hours, 24 hours, 2 weeks or 6 weeks post-injury. Compared to control rats, Peptide5 treated rats showed significant improvement in hindlimb locomotor function between 3 and 6 weeks post-injury and reductions in at-level mechanical allodynia from week 1 post-injury. Immunohistochemistry showed that Peptide5 treatment led to a reduction in total Connexin43 and increased phosphorylated Connexin43 at 8 hours compared to scrambled peptide. At 2 and 6 weeks, lesion size, the astrocytic and the activated macrophage and/or microglial response were all decreased in the Peptide5 animals. Additionally, neuronal cell numbers were higher in the Peptide5 animals compared to the scrambled peptide treated rats at 2 and 6 weeks. These results show for the first time that systemic administration of Peptide5 to block the pathological opening of Connexin43 hemichannels is a feasible treatment strategy in this setting, ameliorating the secondary SCI.
Sutherland, TC, Mathews, KJ, Mao, Y, Nguyen, T & Gorrie, CA 2017, 'Differences in the Cellular Response to Acute Spinal Cord Injury between Developing and Mature Rats Highlights the Potential Significance of the Inflammatory Response.', Frontiers in Cellular Neuroscience, vol. 10, pp. 1-18.View/Download from: UTS OPUS or Publisher's site
There exists a trend for a better functional recovery from spinal cord injury (SCI) in younger patients compared to adults, which is also reported for animal studies; however, the reasons for this are yet to be elucidated. The post injury tissue microenvironment is a complex milieu of cells and signals that interact on multiple levels. Inflammation has been shown to play a significant role in this post injury microenvironment. Endogenous neural progenitor cells (NPC), in the ependymal layer of the central canal, have also been shown to respond and migrate to the lesion site. This study used a mild contusion injury model to compare adult (9 week), juvenile (5 week) and infant (P7) Sprague-Dawley rats at 24 h, 1, 2, and 6 weeks post-injury (n = 108). The innate cells of the inflammatory response were examined using counts of ED1/IBA1 labeled cells. This found a decreased inflammatory response in the infants, compared to the adult and juvenile animals, demonstrated by a decreased neutrophil infiltration and macrophage and microglial activation at all 4 time points. Two other prominent cellular contributors to the post-injury microenvironment, the reactive astrocytes, which eventually form the glial scar, and the NPC were quantitated using GFAP and Nestin immunohistochemistry. After SCI in all 3 ages there was an obvious increase in Nestin staining in the ependymal layer, with long basal processes extending into the parenchyma. This was consistent between age groups early post injury then deviated at 2 weeks. The GFAP results also showed stark differences between the mature and infant animals. These results point to significant differences in the inflammatory response between infants and adults that may contribute to the better recovery indicated by other researchers, as well as differences in the overall injury progression and cellular responses. This may have important consequences if we are able to mirror and manipulate this response in patients of all ages; howev...
Mao, Y, Nguyen, T, Tonkin, RS, Lees, JG, Warren, C, O'Carroll, SJ, Nicholson, LFB, Green, CR, Moalem-Taylor, G & Gorrie, CA 2017, 'Characterisation of Peptide5 systemic administration for treating traumatic spinal cord injured rats.', Experimental Brain Research, vol. 235, no. 10, pp. 3033-3048.View/Download from: UTS OPUS or Publisher's site
Systemic administration of a Connexin43 mimetic peptide, Peptide5, has been shown to reduce secondary tissue damage and improve functional recovery after spinal cord injury (SCI). This study investigated safety measures and potential off-target effects of Peptide5 systemic administration. Rats were subjected to a mild contusion SCI using the New York University impactor. One cohort was injected intraperitoneally with a single dose of fluorescently labelled Peptide5 and euthanised at 2 or 4 h post-injury for peptide distribution analysis. A second cohort received intraperitoneal injections of Peptide5 or a scrambled peptide and was culled at 8 or 24 h post-injury for the analysis of connexin proteins and systemic cytokine profile. We found that Peptide5 did not cross the blood-spinal cord barrier in control animals, but reached the lesion area in the spinal cord-injured animals without entering non-injured tissue. There was no evidence that the systemic administration of Peptide5 modulates Connexin43 protein expression or hemichannel closure in the heart and lung tissue of SCI animals. The expression levels of other major connexin proteins including Connexin30 in astrocytes, Connexin36 in neurons and Connexin47 in oligodendrocytes were also unaltered by systemic delivery of Peptide5 in either the injured or non-injured spinal cords. In addition, systemic delivery of Peptide5 had no significant effect on the plasma levels of cytokines, chemokines or growth factors. These data indicate that the systemic delivery of Peptide5 is unlikely to cause any off-target or adverse effects and may thus be a safe treatment option for traumatic SCI.
Nguyen, T, Mao, Y, Sutherland, T & Gorrie, CA 2017, 'Neural progenitor cells but not astrocytes respond distally to thoracic spinal cord injury in rat models.', Neural regeneration research, vol. 12, no. 11, pp. 1885-1894.View/Download from: UTS OPUS or Publisher's site
Traumatic spinal cord injury (SCI) is a detrimental condition that causes loss of sensory and motor function in an individual. Many complex secondary injury cascades occur after SCI and they offer great potential for therapeutic targeting. In this study, we investigated the response of endogenous neural progenitor cells, astrocytes, and microglia to a localized thoracic SCI throughout the neuroaxis. Twenty-five adult female Sprague-Dawley rats underwent mild-contusion thoracic SCI (n = 9), sham surgery (n = 8), or no surgery (n = 8). Spinal cord and brain tissues were fixed and cut at six regions of the neuroaxis. Immunohistochemistry showed increased reactivity of neural progenitor cell marker nestin in the central canal at all levels of the spinal cord. Increased reactivity of astrocyte-specific marker glial fibrillary acidic protein was found only at the lesion epicenter. The number of activated microglia was significantly increased at the lesion site, and activated microglia extended to the lumbar enlargement. Phagocytic microglia and macrophages were significantly increased only at the lesion site. There were no changes in nestin, glial fibrillary acidic protein, microglia and macrophage response in the third ventricle of rats subjected to mild-contusion thoracic SCI compared to the sham surgery or no surgery. These findings indicate that neural progenitor cells, astrocytes and microglia respond differently to a localized SCI, presumably due to differences in inflammatory signaling. These different cellular responses may have implications in the way that neural progenitor cells can be manipulated for neuroregeneration after SCI. This needs to be further investigated.
Wijesinghe, P, Gorrie, C, Shankar, SK, Chickabasaviah, YT, Amaratunga, D, Hulathduwa, S, Kumara, KS, Samarasinghe, K, Suh, Y-H, Steinbusch, HWM & De Silva, KRD 2017, 'Early stages of Alzheimer's disease are alarming signs in injury deaths caused by traffic accidents in elderly people (≥60 years of age): A neuropathological study.', Indian Journal of Psychiatry, vol. 59, no. 4, pp. 471-477.View/Download from: UTS OPUS or Publisher's site
There is little information available in the literature concerning the contribution of dementia in injury deaths in elderly people (≥60 years).This study was intended to investigate the extent of dementia-related pathologies in the brains of elderly people who died in traffic accidents or by suicide and to compare our findings with age- and sex-matched natural deaths in an elderly population.Autopsy-derived human brain samples from nine injury death victims (5 suicide and 4 traffic accidents) and nine age- and sex-matched natural death victims were screened for neurodegenerative and cerebrovascular pathologies using histopathological and immunohistochemical techniques. For the analysis, Statistical Package for the Social Sciences (SPSS) version 16.0 was used.There was a greater likelihood for Alzheimer's disease (AD)-related changes in the elders who succumbed to traffic accidents (1 out of 4) compared to age- and sex-matched suicides (0 out of 5) or natural deaths (0 out of 9) as assessed by the National Institute on Aging - Alzheimer's Association guidelines. Actual burden of both neurofibrillary tangles (NFTs) and (SPs) was comparatively higher in the brains of traffic accidents, and the mean NFT counts were significantly higher in the region of entorhinal cortex (P < 0.05). However, associations obtained for other dementia-related pathologies were not statistically important.Our findings suggest that early Alzheimer stages may be a contributing factor to injury deaths caused by traffic accidents in elderly people whereas suicidal brain neuropathologies resembled natural deaths.
Mao, Y, Nguyen, T, Sutherland, T & Gorrie, CA 2016, 'Endogenous neural progenitor cells in the repair of the injured spinal cord.', Neural regeneration research, vol. 11, no. 7, pp. 1075-1076.View/Download from: UTS OPUS or Publisher's site
Wijesinghe, P, Shankar, SK, Yasha, TC, Gorrie, C, Amaratunga, D, Hulathduwa, S, Kumara, KS, Samarasinghe, K, Suh, YH, Steinbusch, HW & De Silva, KR 2016, 'Vascular Contributions in Alzheimer's Disease-Related Neuropathological Changes: First Autopsy Evidence from a South Asian Aging Population.', Journal of Alzheimer's Disease, vol. 54, no. 4, pp. 1607-1618.View/Download from: UTS OPUS or Publisher's site
BACKGROUND: Evidence from various consortia on vascular contributions has been inconsistent in determining the etiology of sporadic Alzheimer's disease (AD). OBJECTIVE: To investigate vascular risk factors and cerebrovascular pathologies associated in manifestation of AD-related neuropathological changes of an elderly population. METHODS: Postmortem brain samples from 76 elderly subjects (≥50 years) were used to study genetic polymorphisms, intracranial atherosclerosis of the circle of Willis (IASCW), and microscopic infarcts in deep white matters. From this cohort, 50 brains (≥60 years) were subjected to neuropathological diagnosis using immunohistopathological techniques. RESULTS: Besides the association with age, the apolipoproteinE ɛ4 allele was significantly and strongly associated with Thal amyloid-β phases ≥1 [odds ratio (OR) = 6.76, 95% confidence interval (CI) 1.37-33.45] and inversely with Braak neurofibrillary tangle (NFT) stages ≥III (0.02, 0.0-0.47). Illiterates showed a significant positive association for Braak NFT stages ≥IV (14.62, 1.21-176.73) and a significant negative association for microscopic infarcts (0.15, 0.03-0.71) in deep white matters. With respect to cerebrovascular pathologies, cerebral small vessel lesions (white matter hyperintensities and cerebral amyloid angiopathy) showed a higher degree of associations among them and with AD-related neuropathological changes (p < 0.05) compared to large vessel pathology (IASCW), which showed a significant association only with Braak NFT stages ≥I (p = 0.050). CONCLUSION: These findings suggest that besides age, education, and genetic factors, other vascular risk factors were not associated with AD-related neuropathological changes and urge prompt actions be taken against cerebral small vessel diseases since evidence for effective prevention is still lacking.
Chen, H, Chan, YL, Nguyen, LT, Mao, Y, de Rosa, A, Beh, IT, Chee, C, Oliver, B, Herok, G, Saad, S & Gorrie, C 2016, 'Moderate traumatic brain injury is linked to acute behaviour deficits and long term mitochondrial alterations', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, vol. 43, no. 11, pp. 1107-1114.View/Download from: UTS OPUS or Publisher's site
Wijesinghe, P, Shankar, SK, Chickabasaviah, YT, Gorrie, C, Amaratunga, D, Hulathduwa, S, Kumara, KS, Samarasinghe, K, Suh, YH, Steinbusch, HW & De Silva, KRD 2016, 'Cytoskeletal pathologies of age-related diseases between elderly Sri Lankan (Colombo) and Indian (Bangalore) brain samples', Current Alzheimer Research, vol. 13, no. 3, pp. 268-280.View/Download from: UTS OPUS or Publisher's site
© 2016 Bentham Science Publishers. Within South Asia, Sri Lanka represents fastest aging with 13% of the population was aged over 60's in 2011, whereas in India it was 8%. Majority of the Sri Lankan population based genetic studies have confirmed their origin on Indian mainland. As there were inadequate data on aging cytoskeletal pathologies of these two nations with their close genetic affiliations, we performed a comparison on their elderly. Autopsy brain samples of 50 individuals from Colombo, Sri Lanka (mean age 72.1yrs ± 7.8, mean ± S.D.) and 42 individuals from Bangalore, India (mean age 65.9yrs ± 9.3) were screened for neurodegenerative pathologies using immunohistochemical techniques. A total of 79 cases with incomplete clinical history (Colombo- 47 and Bangalore- 32) were subjected to statistical analysis and 13 cases, clinically diagnosed with dementia and/or Parkinsonism disorders were excluded. As per National Institute on Aging Alzheimer's Association guidelines, between Colombo and Bangalore samples, Alzheimer's disease neuropathologic change for intermediate/ high level was 4.25% vs. 3.12% and low level was 19.15% vs. 15.62% respectively. Pathologies associated with Parkinsonism including brainstem predominant Lewy bodies-6.4% and probable progressive supra nuclear palsy2.13% were found solely in Colombo samples. Alzheimer related pathologies were not different among elders, however, in Colombo males, neurofibrillary tangle grade was significantly higher in the region of hippocampus (odds ratio = 1.46, 95% confidence interval = 0.07-0.7) and at risk in midbrain substantia nigra (p = 0.075). Other age-related pathologies including spongiform changes (p < 0.05) and hippocampus cell loss in dentate gyrus region (p < 0.05) were also identified prominently in Colombo samples. Taken together, aging cytoskeletal pathologies are comparatively higher in elderly Sri Lankans and this might be due to their genetic, dietary and/ or environmental variations.
Mao, Y, Mathews, K & Gorrie, CA 2016, 'Temporal Response of Endogenous Neural Progenitor Cells Following Injury to the Adult Rat Spinal Cord', FRONTIERS IN CELLULAR NEUROSCIENCE, vol. 10.View/Download from: UTS OPUS or Publisher's site
Cawsey, T, Duflou, J, Weickert, CS & Gorrie, CA 2015, 'Nestin-Positive Ependymal Cells Are Increased in the Human Spinal Cord after Traumatic Central Nervous System Injury', JOURNAL OF NEUROTRAUMA, vol. 32, no. 18, pp. 1393-1402.View/Download from: UTS OPUS or Publisher's site
Tonkin, RS, Mao, Y, O'Carroll, SJ, Nicholson, LF, Green, CR, Gorrie, CA & Moalem-Taylor, G 2015, 'Gap junction proteins and their role in spinal cord injury.', Frontiers in Molecular Neuroscience, vol. 7, pp. 1-9.View/Download from: UTS OPUS or Publisher's site
Gap junctions are specialized intercellular communication channels that are formed by two hexameric connexin hemichannels, one provided by each of the two adjacent cells. Gap junctions and hemichannels play an important role in regulating cellular metabolism, signaling, and functions in both normal and pathological conditions. Following spinal cord injury (SCI), there is damage and disturbance to the neuronal elements of the spinal cord including severing of axon tracts and rapid cell death. The initial mechanical disruption is followed by multiple secondary cascades that cause further tissue loss and dysfunction. Recent studies have implicated connexin proteins as playing a critical role in the secondary phase of SCI by propagating death signals through extensive glial networks. In this review, we bring together past and current studies to outline the distribution, changes and roles of various connexins found in neurons and glial cells, before and in response to SCI. We discuss the contribution of pathologically activated connexin proteins, in particular connexin 43, to functional recovery and neuropathic pain, as well as providing an update on potential connexin specific pharmacological agents to treat SCI.
Chan, YL, Saad, S, Simar, D, Oliver, B, McGrath, K, Reyk, DV, Bertrand, PP, Gorrie, C, Pollock, C & Chen, H 2015, 'Short term exendin-4 treatment reduces markers of metabolic disorders in female offspring of obese rat dams', International Journal of Developmental Neuroscience, vol. 46, pp. 67-75.View/Download from: UTS OPUS or Publisher's site
Maternal obesity imposes significant health risks in the offspring including diabetes and dyslipidemia. We previously showed that the hypoglycaemic agent exendin-4 (Ex-4) administered from weaning can reverse the maternal impact of 'transmitted disorders' in such offspring. However daily injection for six-weeks was required and the beneficial effect may lapse upon drug withdrawal. This study aimed to investigate whether short term Ex-4 treatment during suckling period in a rodent model can reverse transmitted metabolic disorders due to maternal obesity.
Maternal obesity was induced in female Sprague Dawley rats by high-fat diet feeding for 6 weeks, throughout gestation and lactation. Female offspring were treated with Ex-4 (5 μg/kg/day) between postnatal day (P) 4 and 14. Female offspring were harvested at weaning (P20). Lipid and glucose metabolic markers were measured in the liver and fat. Appetite regulators were measured in the plasma and hypothalamus.
Maternal obesity significantly increased body weight, fat mass, and liver weight in the offspring. There was an associated inhibition of peroxisomal proliferator activated receptor gamma coactivator 1α (PGC1α), increased fatty acid synthase (FASN) expression in the liver, and reduced adipocyte triglyceride lipase (ATGL) expression. It also increased the plasma gut hormone ghrelin and reduced glucagon-like peptide-1. Ex-4 treatment partially reversed the maternal impact on adiposity and impaired lipid metabolism in the offspring, with increased liver PGC1α and inhibition of FASN mRNA expression. Ex-4 treatment also increased the expression of a novel fat depletion gene a2-zinc-glycoprotein 1 in the fat tissue.
Short term Ex-4 treatment during the suckling period significantly improved the metabolic profile in the offspring from the obese mothers at weaning. Long-term studies are needed to follow such offspring to adulthood to examine the sustained effects of Ex-4 in p...
O'Carroll, SJ, Gorrie, C, Velamoor, S, Green, CR & Nicholson, LF 2013, 'Connexin43 mimetic peptide is neuroprotective and improves function following spinal cord injury', Journal Of Neuroscience Research, vol. 75, no. 3, pp. 256-267.View/Download from: UTS OPUS or Publisher's site
Connexin43 (Cx43) is a gap junction protein up-regulated after spinal cord injury and is involved in the on-going spread of secondary tissue damage. To test whether a connexin43 mimetic peptide (Peptide5) reduces inflammation and tissue damage and improves function in an in vivo model of spinal cord injury, rats were subjected to a 10 g, 12.5 mm weight drop injury at the vertebral level T10 using a MASCIS impactor. Vehicle or connexin43 mimetic peptide was delivered directly to the lesion via intrathecal catheter and osmotic mini-pump for up to 24 h after injury. Treatment with Peptide5 led to significant improvements in hindlimb function as assessed using the BassoBeattieBresnahan scale. Peptide5 caused a reduction in Cx43 protein, increased Cx43 phosphorylation and decreased levels of TNF-a and IL-1ß as assessed by Western blotting. Immunohistochemistry of tissue sections 5 weeks after injury showed reductions in astrocytosis and activated microglia as well as an increase in motor neuron survival. These results show that administration of a connexin mimetic peptide reduces secondary tissue damage after spinal cord injury by reducing gliosis and cytokine release and indicate the clinical potential for mimetic peptides in the treatment of spinal cord patients.
Gorrie, C, Larsen, L & Waite, PM 2013, 'Age and gender differences in perceptions of traffic risk and safety for older pedestrians in metropolitan Sydney, Australia', Journal of Australasian College of Road Safety, vol. 24, no. 4, pp. 28-36.View/Download from: UTS OPUS
Older pedestrians are over represented in serious injury and fatality statistics compared to younger age groups and are considered to be at fault in over 72% of pedestrianmotor vehicle crashes. This study sought to investigate the perceptions of risk and safety in the local traffic environment as reported by older people in the course of everyday pedestrian journeys by asking them to complete a kerb-side survey. The majority of the older pedestrians interviewed (475 women: 265 men) considered that they engaged in safe pedestrian activity and that their own behaviour did not make them vulnerable road users. Perceptions of risk were predominantly associated with external factors such as motorist behaviour and traffic speed. Men tended to be more confident of their own abilities in traffic situations, reported less difficulty crossing roads and paid less attention to route selection than women. Increasing age (65 to 95 years) did not appear to change these perceptions. This is an important consideration for caregivers and medical practitioners when discussing road safety issues with older people, and a critical concern for professionals involved in the planning and implementation of traffic awareness and road safety campaigns for older people.
Lau, NS, Gorrie, C, Chia, YJ, Bilston, LE & Clarke, EC 2013, 'Severity of spinal cord injury in adult and infant rats following vertebral dislocation depends on displacement but not speed', Journal of Neurotrauma, vol. 30, no. 15, pp. 1361-1373.View/Download from: UTS OPUS or Publisher's site
Spinal cord injury (SCI) is less common in children than in adults, but in children it is generally more severe. Spinal loading conditions (speed and displacement) are also thought to affect SCI severity, but the relationship between these parameters is not well understood. This study aimed to investigate the effects of vertebral speed and displacement on the severity of SCI in infants and adults using a rodent model of vertebral dislocation. Thoracolumbar vertebral dislocation was induced in anaesthetized infant rats (~30?g, 13-15 days postnatal, n=40) and adult rats (~250?g, n=57). The 12th thoracic vertebra was secured, whereas the first lumbar vertebra was dislocated laterally. Dislocation speed and magnitude were varied independently and scaled between adults and infants (Adults: 100-250mm/s, 4-10mm; Infants: 40-100mm/s, 1.6-4mm). At 5?h post-injury, rats were euthanized and spinal cords harvested. Spinal cord sections were stained to detect hemorrhage (hematoxylin and eosin) and axonal injury (ß-amyloid precursor protein). For each millimeter increase in vertebral displacement, normalized hemorrhage volume increased by 1.9×10(-3) mm(3) (p=0.028) and normalized area of axonal injury increased by 2.2×10(-1)mm(2) (p<0.001). Normalized hemorrhage volume was 3.3×10(-3) mm(3) greater for infants than for adults (p<0.001). Magnitude of dislocation was found to have a different effect on the normalized area of axonal injury in adults than in infants (p=0.003). Speed of dislocation was not found to have a significant effect on normalized hemorrhage volume (p=0.427) or normalized area of axonal injury (p=0.726) independent of displacement for the range of speeds tested. The findings of this study suggest that both age and amount of spinal motion are key factors in the severity of acute SCI
Wu, A, Lauschke, JL, Gorrie, C, Cameron, N, Hayward, I, Mackay-Sim, A & Waite, PM 2011, 'Delayed olfactory ensheathing cell transplants reduce nociception after dorsal root injury', Experimental Neurology, vol. 229, no. 1, pp. 143-157.View/Download from: UTS OPUS or Publisher's site
Injury to cervical dorsal roots mimics the deafferentation component of brachial plexus injury in humans, with intractable neuropathic pain in the deafferented limb being a common consequence. Such lesions are generally not amenable to surgical repair. The use of olfactory ensheathing cells (OECs) for dorsal root repair, via acute transplantation, has been successful in several studies. From a clinical point of view, delayed transplantation of OECs would provide a more realistic timeframe for repair. In this study we investigated the effect of delayed OEC transplantation on functional recovery of skilled forepaw movements and amelioration of neuropathic pain, using a C7 and C8 dorsal root injury rat model previously established in our lab. We found that OEC transplantation to the dorsal horn 1 week after root injury effectively attenuated neuropathic disturbances associated with dorsal root injury, including spontaneous pain behavior, tactile allodynia and thermal hyperalgesia. The sensory controls of complex, goal-oriented skilled reaching and ladder walking, however, were not improved by delayed OEC transplantation. We did not detect any significant influence of transplanted OECs on injury-induced central reorganisation and afferent sprouting. The anti-nociceptive effect mediated by OEC transplants may therefore be explained by alternative mechanisms such as modification of inflammation and astrogliosis. The significant effect of OEC transplants in mitigating neuropathic pain may be clinically useful in intractable pain syndromes arising from deafferentation. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair.
Hill, F, Kim, CF, Gorrie, C & Moalem-Taylor, G 2011, 'Interleukin-17 deficiency improves locomotor recovery and tissue sparing after spinal cord contusion injury in mice', Neuroscience Letters, vol. 487, no. 3, pp. 363-367.View/Download from: UTS OPUS or Publisher's site
Following the initial impact, spinal cord injury (SCI) triggers a number of inflammatory responses which can exacerbate tissue damage in the cord and impair functional recovery. The involvement of several pro-inflammatory cytokines in the secondary degenerative mechanisms of SCI has been well established, although the role of interleukin-17 (IL-17) remains unclear. In the present study, we used IL-17 knockout (KO) and C57BL/6J wildtype (WT) mice to investigate the effects of IL-17 deficiency on locomotor recovery, lesion size, glial activation and inflammatory cell response following spinal cord contusion injury. Our results show that compared to WT mice, IL-17 KO mice had a significantly smaller lesion size, corresponding with significantly improved locomotor functional recovery following SCI. At 6 weeks after injury, recruitment of B cells, dendritic cells and neutrophils was significantly lower in IL-17 KO than WT mice, however there was no difference in the presence of activated microglia and reactive astrocytes, in the injured spinal cord. These findings suggest that IL-17 is a mediator of secondary degeneration, which contributes to neuroinflammation and hinders functional recovery, though its actions do not affect glial activation following SCI.
Gorrie, C, Hayward, I, Cameron, N, Kailainathan, G, Nandapalan, N, Sutharsan, R, Wang, J, Mackay-sim, A & Waite, P 2010, 'Effects of human OEC-derived cell transplants in rodent spinal cord contusion injury', Brain Research, vol. 1337, no. 1, pp. 8-20.View/Download from: UTS OPUS or Publisher's site
Numerous reports indicate that rodent olfactory ensheathing cells (OECs) assist in spinal cord repair and clinical trials have been undertaken using autologous transplantation of human olfactory ensheathing cells (hOECs) as a treatment for spinal cord in
Gorrie, C.A., Waite, M.E. & Rogers, L.J. 2009, 'Correlations Between Hand Preference and Cortical Thickness in the Secondary Somatosensory (SII) Cortex of the Common Marmoset, Callithrix jacchus (vol 122, pg 1343, 2008)', BEHAVIORAL NEUROSCIENCE, vol. 123, no. 2, pp. 468-III.
Leong, G, Gorrie, C, Ng, K, Rutkowski, S & Waite, P 2009, 'Electrical perceptual threshold testing: A validation study', Journal Of Spinal Cord Medicine, vol. 32, no. 2, pp. 140-146.View/Download from: UTS OPUS
Background/Objective: To investigate inter-rater and intra-rater reliability of electrical perceptual threshold (EPT) testing in assessing somatosensory function in healthy volunteers. Study Design: Prospective experimental. Setting: Hospital-based spina
Gorrie, C, Brown, JS & Waite, P 2008, 'Crash characteristics of older pedestrian fatalities: Dementia pathology may be related to 'at risk' traffic situations', Accident Analysis and Prevention, vol. 40, no. 3, pp. 912-919.View/Download from: UTS OPUS or Publisher's site
Older people are over represented among pedestrian casualties, and cognitive decline is an often cited possible contributory factor. Cognitive decline and dementia are intimately associated, however the role dementia might play in older pedestrian crashe
Gorrie, C, Waite, P & Rogers, L 2008, 'Correlations between hand preference and cortical thickness in the secondary somatosensory (SII) cortex of the common marmoset, Callithrix jacchus', Behavioral Neuroscience, vol. 122, no. 6, pp. 1343-1351.View/Download from: UTS OPUS or Publisher's site
Cortical asymmetries are well established in humans for language and motor regions and correlate with handedness. Here the authors investigate structural differences in the hemispheres of left- and right-handed common marmosets using surface photography
Chase, J, Donaldson, L, Duflou, J & Gorrie, C 2007, 'Safety restraint injuries in fatal motor vehicle collisions', Forensic Science, Medicine, and Pathology, vol. 3, no. 4, pp. 258-263.View/Download from: Publisher's site
The presence of an apparent seat belt mark (SBM) on a car crash occupant is often used as evidence for use of a seat belt at the time of the crash and, conversely, the lack of a SBM is used as an indication that no seat belt was used. This study examined whether there are clear indications of seat belt use to be found at autopsy and evaluated the sensitivity and specificity of apparent SBM and whether the use of a seat belt and seating location affects the type and severity of injuries sustained. Information on the type of injuries sustained and seatbelt use was retrieved from autopsy reports and police reports, respectively, for cases of fatal motor vehicle collisions occurring in Sydney, Australia over a 5-year period. In this study, a SBM was only found on restrained occupants. The proportion of restrained occupants with evidence of a SBM was 36% (sensitivity), whilst unrestrained occupants showed no evidence of a SBM (100% specificity). A SBM was also found to reliably reflect the seating position of the occupant. We conclude that restrained occupants can be expected to show evidence of the seat belt in just over one third of cases and that the absence of a SBM is not necessarily an indication that no seat belt was used. Spurious SBM is very unlikely to be present if the occupant was unrestrained. © 2007 Humana Press Inc.
Gorrie, C, Rodriguez, M, Sachdev, P, Duflou, J & Waite, P 2007, 'Mild neuritic changes are increased in the brains of fatally injured older motor vehicle drivers', Accident Analysis and Prevention, vol. 39, no. 6, pp. 1114-1120.View/Download from: UTS OPUS or Publisher's site
Given the expected increase in the older population and driving in this age group, concerns have been raised about the safety of older drivers. People over 65 years are over-represented in motor vehicle fatalities when calculated by distance driven. They
Peisah, C, Snowdon, J, Gorrie, C, Kril, J & Rodriguez, M 2007, 'Investigation of Alzheimer's disease-related pathology in community dwelling older subjects who committed suicide', Journal Of Affective Disorders, vol. 99, no. 1-3, pp. 127-132.View/Download from: UTS OPUS or Publisher's site
Background: Older people have a higher risk of completed suicide than any other age group worldwide. The contribution of neurodegenerative disease to this risk remains controversial. Aims: To investigate prevalence of Alzheimer's disease-related (AD) pat
Deng, C, Gorrie, C, Hayward, I, Elston, B, Venn, M, Mackay-sim, A & Waite, P 2006, 'Survival and migration of human and rat olfactory ensheathing cells in intact and injured spinal cord', Journal Of Neuroscience Research, vol. 83, no. 7, pp. 1201-1212.View/Download from: UTS OPUS or Publisher's site
Increasing evidence indicates the potential of olfactory ensheathing cells (OECs) for treating spinal cord injuries. The present study compared proliferation and migration of adult rat and human OECs transplanted into the spinal cord of athymic (immunode
Gorrie, C, Rodriguez, M, Sachdev, P, Duflou, J & Waite, P 2006, 'Increased neurofibrillary tangles in the brains of older pedestrians killed in traffic accidents', Dementia And Geriatric Cognitive Disorders, vol. 22, no. 1, pp. 20-26.View/Download from: UTS OPUS or Publisher's site
Background/Aims: Older people are over-represented in pedestrian fatalities, and it has been suggested that the presence of cognitive impairment or dementia in these individuals may contribute to their accidents. Using neuropathological methods, we aimed
Waite, P, Gorrie, C, Herath, N & Marotte, L 2006, 'Whisker maps in marsupials: Nerve lesions and critical periods', Anatomical Record, vol. 288A, no. 2, pp. 174-181.View/Download from: UTS OPUS or Publisher's site
In the wallaby, whisker-related patterns develop over a protracted period of postnatal maturation in the pouch. Afferents arrive simultaneously in the thalamus and cortex from postnatal day (P) 15. Whisker-related patterns are first seen in the thalamus
Potas, J, Zheng, Y, Moussa, C, Venn, M, Gorrie, C, Deng, C & Waite, P 2006, 'Augmented locomotor recovery after spinal cord injury in the athymic nude rat', Journal Of Neurotrauma, vol. 23, no. 5, pp. 660-673.View/Download from: UTS OPUS or Publisher's site
The immune response contributes to ongoing secondary tissue destruction following spinal cord injury (SCI). Although infiltrating neutrophils and monocytes have been well studied in this process, T-cells have received less attention. The objective of thi
Gorrie, C, Oakes, SR, Duflou, J, Blumbergs, P & Waite, P 2002, 'Axonal injury in children after motor vehicle crashes: Extent, distribution, and size of axonal swellings using beta-APP immunohistochemistry', Journal Of Neurotrauma, vol. 19, no. 10, pp. 1171-1182.View/Download from: Publisher's site
The brains of 32 children (3 months to 16 years) who died as a result of motor vehicle collisions were examined for axonal injury using,beta-APP immunohistochemistry. The extent and distribution of axonal injury was assessed and quantified throughout the
Gorrie, C, Duflou, J, Brown, JS, Gibson, T & Waite, P 2001, 'Extent and distribution of vascular brain injury in pediatric road fatalities', Journal Of Neurotrauma, vol. 18, no. 9, pp. 849-860.View/Download from: Publisher's site
This study used a multidisciplinary approach to examine the brains of pediatric road trauma fatalities in the Sydney area over a 3-year period. The brains of 32 children (0-16 years) were examined: 20 pedestrians, nine passengers, and three cyclists. The
Waite, P.M.E., Gorrie, C.A., Benetatos, E., Brown, J., Duflou, J. & Gibson, T. 2000, 'Neuropathology in children following fatal road trauma', EUROPEAN JOURNAL OF NEUROSCIENCE, vol. 12, pp. 223-223.
Gorrie, C, Duflou, J, Brown, JS & Waite, P 1999, 'Fatal head injury in children: a new approach to scoring axonal and vascular damage', Childs Nervous System, vol. 15, no. 6-7, pp. 322-327.View/Download from: Publisher's site
As part of a multidisciplinary study of brain damage in children fatally injured in motor vehicle accidents, a simple method to quantify and visualise the distribution and extent of injury has been developed. Vascular and axonal injury were assessed usin
Watterson, P, Gorrie, C & Herok, G 2019, 'HUMAN TRIAL OF MEDIAN NERVE ACTIVATION BY HIGH SPEED ROTATION OF A BIPOLE MAGNET CONFIGURATION', International Neuromodulation Society 14th World Congress, Sydney, Australia.
Moalem-Taylor, G, Mao, Y, Tonkin, R, Nguyen, T, O'Carroll, S, Nicholson, L, Green, C & Gorrie, C 2015, 'Systemic delivery of a mimetic peptide against CONNEXIN43 GAP junction protein in rats following spinal cord injury', JOURNAL OF NEUROCHEMISTRY, 25th Biennial Meeting of the International-Society-for-Neurochemistry Jointly with the 13th Meeting of the Asian-Pacific-Society-for-Neurochemistry in Conjunction with the 35th Meeting of the Australasian-Neuroscience-Society, WILEY-BLACKWELL, Cairns, AUSTRALIA, pp. 361-361.View/Download from: UTS OPUS
Gorrie, C.A., Rodrigue, M.L., Duflou, J., Sachdev, P. & Waite, P.M.E. 2004, 'Older pedestrian fatalities: Assessment of dementia related neuropathology', JOURNAL OF NEUROTRAUMA, pp. 1314-1314.
Dr Gorrie collaborates with researchers from
- University of New South Wales
- Neuroscience Research Australia
- University of Auckland
- University of Sri Jayewardenepura
- University of Sydney