Turmeric has been in use since ancient times as a condiment and due to its medicinal properties. Curcumin, the yellow colouring principle in turmeric, is polyphenolic and major active constituent. Besides anti-inflammatory, thrombolytic and anticarcinogenic activities, curcumin also possesses strong antioxidant property. In view of the novel combination of properties, neuroprotective efficacy of curcumin was studied in rat middle cerebral artery occlusion (MCAO) model. Rats were subjected to 2 h of focal ischemia followed by 72 h of reperfusion. They were pre-treated with curcumin (100 mg/kg, po) for 5 days prior to MCAO and for another 3 days after MCAO. The parameters studied were behavioural, biochemical and histological. Treatment with curcumin could significantly improve neurobehavioral performance compared to untreated ischemic rats as judged by its effect on rota-rod performance and grid walking. A significant inhibition in lipid peroxidation and an increase in superoxide dismutase (SOD) activity in corpus striatum and cerebral cortex was observed following treatment with curcumin in MCAO rats as compared to MCAO group. Intracellular calcium levels were decreased following treatment with curcumin in MCAO rats. Histologically, a reduction in the infarct area from 33% to 24% was observed in MCAO rats treated with curcumin. The study demonstrates the protective efficacy of curcumin in rat MCAO model.

BACKGROUND: Cerebral ischemia increases neurogenesis in the subventricular zone (SVZ) and in the subgranular zone (SGZ) of the dentate gyrus, and this might be modulated by an enriched environment including voluntary physical activity. We examined whether enforced physical training (EPT) influences neurogenesis in the SVZ and SGZ after cerebral ischemia.

METHODS: Adult male Sprague-Dawley rats were subjected to focal cerebral ischemia for 2 h, and divided into an EPT and a non-EPT group. All rats in the EPT group were trained using a rota-rod for 14 days. 5-bromo-2'-deoxyuridine (BrdU) was injected to determine levels of cell proliferation. Functional recovery was assessed using a set of behavioral test batteries. Extents of endogenous neurogenesis in the SVZ and SGZ were quantified by immunofluorescence staining. Although final infarction volumes were not significantly different in the groups, functional recovery was better in the EPT group at 10 and 17 days after ischemia. In the SVZ, BrdU labeling and double labeling of BrdU/Dcx and of BrdU/NeuN were not significantly different in the two groups. However, in the SGZ, EPT significantly increased the number of BrdU-positive cell numbers (EPT vs. non-EPT: 159.1+/-19.9 vs. 101.8+/-7.8, p=0.04), and the number of BrdU/Dcx double-labeled cells (130.6+/-16.9 vs. 73.6+/-7.2, p=0.01).

CONCLUSIONS: The results obtained indicate that EPT promotes neurogenesis in the SGZ of the dentate gyrus after ischemia, but not in the SVZ. The biochemical mechanism that determines the differential effects of EPT remains to be clarified.

Stroke is a major cause of death worldwide. Previous studies have suggested both exercise and mitochondrial biogenesis contribute to improved post-ischemic recovery of brain function. However, the exact mechanism underlying this effect is unclear. On the other hand, the benefit of exercise-induced mitochondrial biogenesis in brain has been confirmed. In this study, we attempted to determine whether treadmill exercise induces functional improvement through regulation of mitochondrial biogenesis after brain ischemia. We subjected adult male rats to ischemia, followed by either treadmill exercise or non-exercise and analyzed the effect of exercise on the amount of mitochondrial DNA (mtDNA), expression of mitochondrial biogenesis factors, and mitochondrial protein. In the ischemia-exercise group, only peroxisome proliferator activated receptor coactivator-1 (PGC-1) expression was increased significantly after 3 days of treadmill training. However, after 7 days of training, the levels of mtDNA, nuclear respiratory factor 1, NRF-1, mitochondrial transcription factor A, TFAM, and the mitochondrial protein cytochrome C oxidase subunit IV (COXIV) and heat shock protein-60 (HSP60) also increased above levels observed in non-exercised ischemic animals. These changes followed with significant changes in behavioral scores and cerebral infarct volume. The results indicate that exercise can promote mitochondrial biogenesis after ischemic injury, which may serve as a novel component of exercise-induced repair mechanisms of the brain. Understanding the molecular basis for exercise-induced neuroprotection may be beneficial in the development of therapeutic approaches for brain recovery from the ischemic injury. Based upon our findings, stimulation or enhancement of mitochondrial biogenesis may prove a novel neuroprotective strategy in the future.

BACKGROUND AND PURPOSE: Studies suggest that after brain injury, hyperbaric oxygen (HBO2) is neuroprotective by stimulating cell proliferation. We examine whether HBO2 promotes neural stem cells (NSC) to proliferate and differentiate in neonatal hypoxic-ischemic (HI) rats. METHODS: Seven-day-old rat pups were subjected to unilateral carotid artery ligation followed by 2 hours of hypoxia (8% O2). HBO2 was administered (2 ATA (atmospheres absolutes), once daily for 7 days) within 3 hours after HI. The proliferating neural stem cells in the subventricular zone (SVZ) and dentate gyrus (DG) were dynamically examined by 5-bromo-2-deoxyuridine (BrdU)/nestin immunofluorescence. Nestin protein was detected by western blot analysis at various time points (from 6 hours to 14 days) after HI. The migrating NSC were examined by BrdU/doublecortin (DCX) immunofluorescence 7 and 14 days after HI. The phenotype of the newborn cells was identified by BrdU/beta-tubulin, BrdU/ glial fibrillary acidic protein (GFAP) and BrdU/O4 (oligodendrocyte marker) immunofluorescence. Myelin basic protein (MBP) was examined by immunohistochemistry and pathological changes of the brain tissue were detected 28 days after HI. RESULTS: In neonatal HI rats treated with HBO2, the proliferation of endogenous NSC was observed in the SVZ and DG. Cell numbers peaked 7 days after HI and proliferating NSC migrated to the cerebral cortex at 14 d after HI. Twenty-eight days after HI, an increase in newly generated neurons, oligodendrocytes and MBP was observed in the HBO2 group compared to the untreated and HI-treated rats. CONCLUSIONS: This study suggests that HBO2 treatment may promote neurogenesis of the endogenous NSC in neonatal HI rats, contributing to repair of the injured brain.