Our laboratory previously found that protein-energy malnutrition (PEM) existing prior to brain ischemia impaired functional outcome measured in an open field test, and one-third of animals showed a marked increase in reactive gliosis. It was hypothesized that PEM worsened stroke outcome by increasing inflammation via increased activation of the transcription factor, nuclear factor kappa B (NFκB). Mongolian gerbils (11-12 wk old) were randomly assigned to a control diet (12.5% protein) or a protein-deficient diet (2%) for 28 days. The control group on average gained 4.9g and the PEM group lost 7.4g. PEM gerbils had significantly decreased food intake (P<0.001; unpaired t-test). Animals were then subjected to global ischemia or sham surgery, resulting in four experimental groups. Global ischemia was achieved by a 5 min bilateral common carotid artery occlusion with tympanic temperature regulated at 36.5 ± 0.2C. PEM independently increased hippocampal NFκB activation by three times higher than control diet animals at 6hr after surgery (p=0.014; 2-factor ANOVA) detected by electrophoretic mobility shift assay (EMSA). There was no significant effect of ischemia on NFκB activation and there was no interaction of diet and ischemia. Serum glucose and serum cortisol were also measured since both variables can be affected by PEM and can influence stroke outcome, but there was no significant effect of diet or ischemia. Because of the increased NFκB activation observed in PEM-Sham animals, a second experiment investigated if PEM also increased NFκB activation in the absence of surgery. Gerbils of the same age were randomly assigned to either control diet or PEM for 28 days but did not receive any surgery. PEM consistently increased NFκB activation. Since PEM exists in 16% of elderly stroke patients at admission, the data suggest that PEM may worsen stroke outcome through increased activation of NFκB. Because increased NFκB activation was also observed in PEM independent of ischemia, the data also have implications for the inflammatory response of protein-energy malnourished elderly in general.

Our laboratory previously found that protein-energy malnutrition (PEM) existing prior to brain ischemia impaired functional outcome measured in an open field test, and one-third of animals showed a marked increase in reactive gliosis. It was hypothesized that PEM worsened stroke outcome by increasing inflammation via increased activation of the transcription factor, nuclear factor kappa B (NFκB). Mongolian gerbils (11-12 wk old) were randomly assigned to a control diet (12.5% protein) or a protein-deficient diet (2%) for 28 days. The control group on average gained 4.9g and the PEM group lost 7.4g. PEM gerbils had significantly decreased food intake (P<0.001; unpaired t-test). Animals were then subjected to global ischemia or sham surgery, resulting in four experimental groups. Global ischemia was achieved by a 5 min bilateral common carotid artery occlusion with tympanic temperature regulated at 36.5 ± 0.2C. PEM independently increased hippocampal NFκB activation by three times higher than control diet animals at 6hr after surgery (p=0.014; 2-factor ANOVA) detected by electrophoretic mobility shift assay (EMSA). There was no significant effect of ischemia on NFκB activation and there was no interaction of diet and ischemia. Serum glucose and serum cortisol were also measured since both variables can be affected by PEM and can influence stroke outcome, but there was no significant effect of diet or ischemia. Because of the increased NFκB activation observed in PEM-Sham animals, a second experiment investigated if PEM also increased NFκB activation in the absence of surgery. Gerbils of the same age were randomly assigned to either control diet or PEM for 28 days but did not receive any surgery. PEM consistently increased NFκB activation. Since PEM exists in 16% of elderly stroke patients at admission, the data suggest that PEM may worsen stroke outcome through increased activation of NFκB. Because increased NFκB activation was also observed in PEM independent of ischemia, the data also have implications for the inflammatory response of protein-energy malnourished elderly in general.

No description available.

The present thesis investigated the effects of a western diet (WD) on cell death and functional outcome following global ischemia in rats. Experiment 1 assessed the effects of a 60-day WD regimen on temperature, activity and glucose levels in normal rats. Experiment 2 evaluated the influence of a 60-day WD regimen on hippocampal CA1 injury and cognition following global ischemia. Results from experiment 1 revealed significant differences in activity levels only; animals fed the WD were less active than control diet animals. Results from experiment 2 suggested that a WD did not aggravate CA1 injury or behavioral deficits. The second portion of my thesis examined the effects of a 120-day WD regimen on stroke severity and cognition following global ischemia. Briefly, the surgical protocol used to induce a global ischemic insult did not produce consistent damage across all animals. Plausible reasons for this surgical variability and future directions are discussed.

L’arrêt cardio circulatoire et le traumatisme crânien sont responsables de lésions cérébrales dont les conséquences médico économiques sont un réel enjeu de santé publique. Malgré des espoirs importants lors des travaux expérimentaux, la majorité des traitements neuroprotecteurs se sont révélés être des échecs lors du passage à la clinique humaine. Riche d’une expérience clinique vieille de plusieurs millénaires, la Médecine Chinoise Traditionnelle a démontré son efficacité en clinique sur des patients victimes d’accidents vasculaires cérébraux. Le MLC 601, et sa formule simplifiée le MLC901, produits issus de celle-ci, ont déjà été étudiés dans un travail expérimental réalisé sur un modèle d'ischémie focale dans le laboratoire d’accueil. L’effet pléiotrope du produit avait alors été souligné. L’objet de notre travail a été d’étudier les effets neuroprotecteurs et neurorégénérateurs du MLC901 sur 2 autres modèles expérimentaux de lésions cérébrales : l’ischémie globale, mimant les conséquences cérébrales d’un arrêt cardiaque et le traumatisme crânien par percussion liquidienne latérale. Nous insistons, dans ce travail, sur l’effet neuroprotecteur du produit agissant sur les mécanismes de nécrose, d’apoptose et de stress oxydant se mettant en place après la lésion initiale. Nous retrouvons également une action neurorégénérative avec une stimulation de la neurogenèse induite par la lésion. L’ensemble de ces mécanismes cellulaires mis en place est associé à une amélioration de la récupération des fonctions neurologiques des animaux mis en évidence par l'utilisation de tests comportementaux moteurs et cognitifs. Nous démontrons donc dans ce travail, l’effet neuroprotecteur et neurorégénérateur du MLC901 sur deux modèles expérimentaux de « cérébro lésion », l’un ischémique et l’autre traumatique. / Cardiac arrest and traumatic brain injury are a socio economic health problem. Despite lot of hopes on neuroprotective therapies, few confirmed promising experimental results in clinical studies. Traditional Chinese Medicine has been used for several centuries. Despite lot of clinical investigations, few data are available on mechanisms involved in their effects. Interesting results have been published in stroke patients, and experimental studies using MLC601 and MLC901 have been conducted in mouse focal ischemia models. The multiple mechanisms of action, neuroprotective and neuroregenerative, of these treatments have been highlighted. The purpose of our study was to analyse the neuroprotective and neuroregenerative actions of MLC901 on rat global ischemia and traumatic brain injury models. In these models, we confirmed the neuroprotective action on necrosis, apoptosis and oxidative stress and the neuroregenerative action by the way of neurogenesis activation. These cellular actions are associated with functional recovery in the two models. We confirmed in these two experimental models, the neuroprotective and neuroregenerative effects of MLC901 on post ischemic or post traumatic brain injuries. This approach is essential for Traditional Chinese Medicine to be accepted by occidental one.

Post-ischemia depression (PID) is a condition that affects approximately 30% of survivors from stroke or cardiac arrest and has an important impact on patients’ quality of life. Previous studies support important roles of the endocannabinoid (eCB) system in depression and brain ischemia. This study attempts to link all three variables together by investigating the role and mechanism of eCB signaling in the development of PID. A global ischemia + hypotension model was used to induce a PID phenotype in CD1 mice. Three ischemic time frames were tested, and even though all three could induce significant cell death in the CA1 region of the hippocampus, only the 15-minute time point led to an increased immobility time on the forced swimming test (FST). The main goal of this study was to investigate the effect of a cannabinoid type-I receptor (CB1R) antagonist/inverse agonist, AM281, on the development of two depressive symptoms: anhedonia, measured with the sucrose preference test (SPT), and behavioral despair, measured with the FST. AM281 administration was able to significantly reduce the symptoms of anhedonia and behavioural despair. Subsequently, the mechanism behind this antidepressant-like effect was investigated. Administration of bicuculine with AM281 did not significantly affect the antidepressant effect on the FST, therefore suggesting that AM281 does not act on GABAergic synapses. A similar protocol was adopted with NVP-AM077, where its administration combined with AM281 was able to block the effect of AM281, thus confirming the importance of glutamatergic synapses for the antidepressant effect of AM281. Furthermore, the administration of a TAT-GLUR2 peptide did not significantly affect the effect of AM281, implying that the astroglial cell-mediated LTD (long-term depression) at glutamatergic synapses is not involved in the antidepressant effects of AM281. Finally, a bilateral intra-BLA (basolateral nucleus of the amygdala) administration of AM281 was able to reduce the immobility time on the FST. In conclusion, these results highlight the important contribution of BLA glutamatergic synapses to the antidepressant-like effect conferred by AM281.

No description available.

No description available.

The aim of this thesis is to describe the variability of cardiac rhythm and familiarity with the methods of the analysis, ie by monitoring changes in heart rhythm electrogram signal recording and using the methods in the time domain using recurrent diagram. The work describes the quantification of the methods and possibilities of quantifiers in the evaluation of heart rate variability analysis. It also describes the clinical significance of heart rate variability and diagnostic capabilities changes of heart rate variability caused by ischemic heart disease. The practical part describes how to create applications in Matlab to calculate the quantifiers analysis of heart rate variability in the time domain using recurrent diagram. The calculation was made of the positions R wave elektrogram signal isolated rabbit hearts. The calculated values of quantifiers both methods were statistically evaluated and discussed.