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L’inflammation est un processus essentiel à prendre en compte dans la pratique clinique. Nous avons montré durant cette thèse que le statut (neuro)inflammatoire précédant la survenue d’une pathologie cérébrale est à prendre en compte nécessairement puisqu’il modifie drastiquement la réponse inflammatoire suite à un deuxième stimulus comme la survenue d’un AVC. Il est d’autant plus important que 90% des AVC sont associés à des comorbidités comme l’hypertension artérielle, le diabète ou la consommation chronique d’alcool, qui ont d’ores et déjà été décrites comme des maladies avec une composante inflammatoire. Nous avons caractérisé ce statut neuroinflammatoire silencieux, aussi appelé priming, dans le cadre de la consommation chronique d’alcool et dans le traumatisme crânien léger. De plus, nous avons identifié les macrophages périvasculaires comme participants à l’effet aggravateur du priming inflammatoire sur les lésions ischémiques. Ils semblent alors être une cible thérapeutique de choix et feront l’objet de futures études. Il est donc nécessaire de trouver des techniques d’imagerie non invasives pour détecter le priming. L’autoradiographie ciblant le TSPO nous a permis de révéler le priming inflammatoire dans le cadre du traumatisme crânien léger. Nous proposons, au vu de nos résultats obtenus durant cette thèse, la tomographie par émission de positons pour la détection de la neuroinflammation invisible dans les atteintes cérébrales aigüe(s) et chronique(s). / Inflammation is an essential process to be considered in clinical practice. We have shown during this thesis that the (neuro)inflammatory status preceding the occurrence of a cerebral pathology must necessarily be taken into account since it drastically modifies the inflammatory response following a second stimulus such as stroke. This is even more important given that 90% of strokes are associated with comorbidities such as chronic hypertension, diabetes or chronic alcohol consumption, for which inflammation is an important pathophysiological feature. We have characterized this silent inflammatory status, also called priming, in the context of chronic alcohol consumption and in mild traumatic brain injury. We have identified perivascular macrophages (PVM) as mediators of the aggravating effect of inflammatory priming on ischemic stroke. PVM appear to be potential therapeutic targets and will be the subject of future investigations. It is therefore necessary to find non-invasive imaging techniques to detect inflammatory priming. We show that autoradiography targeting TSPO reveals the inflammatory priming provoked by a single mild traumatic brain injury. We propose, in light of the results obtained during this thesis, the positron emission tomography imaging to detect the invisible neuroinflammation in acute and chronic brain diseases.

Introduction: Previous research describes significant associations between criminal offending behaviour and traumatic brain injury (TBI). In young offenders, particularly, TBI is significantly more prevalent than in the general youth population. This association might be explained by the fact that key TBI sequelae (e.g., aggression, behavioural and cognitive impulsivity, emotional dysregulation) can place individuals at risk for criminal offending. However, at least two critical questions remain relatively under-investigated: Is there crossnational variability in the prevalence of TBI in young offenders and in the emotional, behavioural, and cognitive profile of young offenders with and without TBI? Few studies report on prevalence of TBI in young offender populations from low- or middle-income countries (LMICs), and fewer describe the neuropsychological profiles of TBI-afflicted young offenders from LMICs. Method: Participants were a South African sample of 25 young offenders and 56 non-offender controls. Conducting such investigations in South Africa is valuable because (a) crime rates, particularly those related to violent offences, are higher in this country than elsewhere in the world, and (b) the prevalence of TBI in South Africa is three times the global rate. All participants were administered self-report measures of emotion regulation, aggression, antisocial behaviour, as well as standardized tests of various executive functions (planning, cognitive flexibility, generative fluency, inhibition, problem solving, and rule learning/maintenance) from the Delis-Kaplan Executive Function System (D-KEFS) battery. I also gathered self-report information about their history of TBI, including whether it was accompanied by loss of consciousness (LoC). Results: Prevalence of TBI was higher in offenders (n = 18/25; 72%) than in non-offenders (n = 24/56; 43%). Offenders reported experiencing more severe TBI: The distribution of TBI with LoC was significantly different across offender and non-offender groups, p < .001. Analyses detected significant main effects of offender status on all outcomes; significant main effects of TBI on emotion regulation, aggression, and antisocial behaviour; and significant offender x TBI interaction effects on emotion regulation and aggression, ps < .036. Conclusion: These findings are broadly consistent with previous studies in this literature. Hence, the present study confirms the importance of understanding associations between TBI and offending (particularly in LMICs) and how the co-occurrence of the two is predictable and can have cumulative effects on affect, behaviour, and cognition. Because sustaining a TBI is preventable, describing the risk for negative outcomes and the socioeconomic costs thereof can inform policy development, rehabilitation planning, and initiatives to reduce recidivism rates.

Traumatic brain injury (TBI) and its associated neural and cognitive sequelae are of increasing interest in military populations. Blast-related TBI is becoming more commonplace in military Service Members and Veterans since Operation Iraqi Freedom/Operation Enduring Freedom/Operation New Dawn and their following conflicts. It is currently unclear whether blast-related injuries cause unique neural and cognitive deficits. The present investigation, in Study 1, aims to investigate the differences in blast-related and non-blast related TBI using traditional statistical techniques. In Study 2, this study will demonstrate the use of Qualitative Comparative Analysis (QCA) in diffusion tensor imaging data. QCA is a relatively new technique that examines configurations of variables that lead to a predefined outcome. QCA has the ability to uncover configurations of variables not yet considered in empirical literature, which may contribute new perspectives on the many different variables often associated with brain injury. Study 1 demonstrated no significant differences between uninjured and injured subjects in white matter integrity, and no differences between blast-related and non-blast related mechanisms. Study 2 demonstrated limited support for the use of QCA in diffusion tensor imaging. Evidence for the use of this method in other neuroimaging modalities is reviewed

Magister Artium (Social Work) - MA(SW) / Recovery from traumatic brain injury (TBI) can be a lengthy and challenging process for survivors, their families, and health and welfare services. Globally, South Africa has the second-highest prevalence of TBI that is due to road traffic accidents. The growing challenges for TBI survivors are the financial constraints, health implications, and the psychosocial support required by survivors of TBI and their families, which impacts family reintegration, post-hospitalisation. The aim of the study was to understand the challenges experienced by TBI survivors with regards to the psychosocial support services for family reintegration. A qualitative approach, using an exploratory-descriptive design was used. The person-centred perspective was chosen as a theoretical framework.

Resistance to tissue hypoxia is a robust fundamental adaptation to low oxygen supply, and represents a novel neuroscience problem with significance to mammalian physiology as well as human health. With the underlying mechanisms strongly conserved in evolution, the ability to resist tissue hypoxia in natural systems has recently emerged as an interesting model in mammalian physiology research to understand mechanisms that can be manipulated for the clinical management of stroke. The extraordinary ability to resist tissue hypoxia by the naked mole rat (NMR) indicates the presence of a unique mechanism that underlies the remarkable healthy life span and exceptional hypoxia resistance. This opens an interesting line of research into understanding the mechanisms employed by the naked mole rat (. Heterocephalus glaber) to protect the brain during hypoxia. In a series of studies, we first examined the presence of neuroprotection in the brain cells of naked mole rats (NMRs) subjected to hypoxic insults, and then characterized the expression of such neuroprotection in a wide range of time intervals. We used oxygen nutrient deprivation (OND), an in vitro model of resistance to tissue hypoxia to determine whether there is evidence of neuronal survival in the hippocampal (CA1) slices of NMRs that are subjected to chronic hypoxia. Hippocampus neurons of NMRs that were kept in hypoxic condition consistently tolerated OND right from the onset time of 5. h. This tolerance was maintained for 24. h. This finding indicates that there is evidence of resistance to tissue hypoxia by CA1 neurons of NMRs. We further examined the effect of hypoxia on metabolic rate in the NMR. Repeated measurement of metabolic rates during exposure of naked mole rats to hypoxia over a constant ambient temperature indicates that hypoxia significantly decreased metabolic rates in the NMR, suggesting that the observed decline in metabolic rate during hypoxia may contribute to the adaptive mechanism used by the NMR to resist tissue hypoxia. This work is aimed to contribute to the understanding of mechanisms of resistance to tissue hypoxia in the NMR as an important life-sustaining process, which can be translated into therapeutic interventions during stroke.

Resistance to tissue hypoxia is a robust fundamental adaptation to low oxygen supply, and represents a novel neuroscience problem with significance to mammalian physiology as well as human health. With the underlying mechanisms strongly conserved in evolution, the ability to resist tissue hypoxia in natural systems has recently emerged as an interesting model in mammalian physiology research to understand mechanisms that can be manipulated for the clinical management of stroke. The extraordinary ability to resist tissue hypoxia by the naked mole rat (NMR) indicates the presence of a unique mechanism that underlies the remarkable healthy life span and exceptional hypoxia resistance. This opens an interesting line of research into understanding the mechanisms employed by the naked mole rat (. Heterocephalus glaber) to protect the brain during hypoxia. In a series of studies, we first examined the presence of neuroprotection in the brain cells of naked mole rats (NMRs) subjected to hypoxic insults, and then characterized the expression of such neuroprotection in a wide range of time intervals. We used oxygen nutrient deprivation (OND), an in vitro model of resistance to tissue hypoxia to determine whether there is evidence of neuronal survival in the hippocampal (CA1) slices of NMRs that are subjected to chronic hypoxia. Hippocampus neurons of NMRs that were kept in hypoxic condition consistently tolerated OND right from the onset time of 5. h. This tolerance was maintained for 24. h. This finding indicates that there is evidence of resistance to tissue hypoxia by CA1 neurons of NMRs. We further examined the effect of hypoxia on metabolic rate in the NMR. Repeated measurement of metabolic rates during exposure of naked mole rats to hypoxia over a constant ambient temperature indicates that hypoxia significantly decreased metabolic rates in the NMR, suggesting that the observed decline in metabolic rate during hypoxia may contribute to the adaptive mechanism used by the NMR to resist tissue hypoxia. This work is aimed to contribute to the understanding of mechanisms of resistance to tissue hypoxia in the NMR as an important life-sustaining process, which can be translated into therapeutic interventions during stroke.

7,8-Dihydroxy-4-methylcoumarin (Dhmc) is a precursor in the synthesis of derivatives of 4-methyl coumarin, which has excellent radical scavenging properties. In this study, we investigated whether Dhmc protects against oxidative stress and ischemic brain injury. We found that Dhmc protected against glutamate toxicity in hippocampal HT-22 cells in a concentration-dependent manner in vitro. Dhmc inhibited glutamate-induced glutathione depletion and generation of reactive oxygen species, suggesting that Dhmc has an antioxidant effect. In addition, Dhmc inhibited glutamate-induced depletion of hippocalcin, a protein that buffers intracellular calcium and prevents calcium-induced cell death. In our in vivo studies, Dhmc reduced infarct volume in neonatal rats when administered 4 h after cerebral hypoxia/ischemia injury and attenuated the hypoxia/ischemia injury-induced decrease of hippocalcin expression in neonatal rats. Taken together, these results suggest that Dhmc prevents glutamate-induced toxicity by scavenging free radicals and regulating hippocalcin expression. Dhmc may represent a promising agent in the treatment of acute and chronic neurological disorders induced by oxidative stress.