curcumin and Cerebral-Infarction

The aim of this study was to determine the protective effects of curcumin on memory, hippocampal acetylcholine level and apoptosis in a rat model of repeated cerebral ischemia. Male Wistar rats were divided into sham rats that received saline and the other 3 groups underwent 4-vessel occlusion brain ischemia (4VOI), received oral administration of either saline or curcumin at doses rate of 25mg/kg/day and 50mg/kg/day for 7 days. Memory function was evaluated by eight-arm radial maze task and Morris water maze (MWM) test, Acetylcholine release (ACh) in the dorsal hippocampus was evaluated by microdialysis-HPLC) and neuron apoptosis was investigated by terminal deoxynucleotidyltransferase mediated fluorescein-deoxyuridine triphosphate nick-end labeling. 4VOI test reviled impaired memory, reduced dorsal hippocampus Ach level and induced apoptosis in the Repeated Cerebral Ischemia rat model. Curcumin significantly improved the memory deficit (p<0.001), increased Ach level (p<0.001) and prevented hippocampal neuron apoptosis (p<0.001). Curcumin may be suggested as a promising therapy for ischemic cerebrovascular dementia and its beneficial effect is due to its memory preserving, ACh-increasing and neuroprotective effects in the rat.

Topics: Acetylcholine; Animals; Brain Ischemia; Cerebral Infarction; Curcumin; Hippocampus; Male; Maze Learning; Memory Disorders; Rats; Rats, Wistar

To investigate whether curcumin promotes hippocampal neurogenesis in the cerebral ischemia (CI) mice via Wnt/β-catenin signaling pathway.. Male C57BL/6 mice were randomly divided into groups: sham operation group (Sham), cerebral ischemic group (CI), curcumin treatment group (50, 100 mg/kg/d, i.p.) and curcumin (100 mg/kg/d) + DKK1 (a blocker of Wnt receptor, 200 ng/d, icv) group. CI was induced by bilateral common carotid arteries occlusion (BCCAO) for 20 min. The Morris water maze test was conducted to detect spatial learning and memory. Immunofluorescence staining was used to examine the proliferation and differentiation of immature neurons in the hippocampal dentate gyrus. The proteins involved in neurogenesis and Wnt signaling pathway were examined using Western blot assay.. Curcumin significantly alleviated cognitive deficits induced by CI. Curcumin dose-dependently increased the proliferation of neural stem cells and promoted the differentiation and maturation of newly generated neural cells into neurons. Curcumin also increased the expression of proteins involved in neurogenesis (including Ngn2, Pax6 and NeuroD 1) and the Wnt/β-catenin signaling pathway. Moreover, the forenamed effects of curcumin were abolished by pretreatment with DKK1, a blocker of Wnt receptor.. Curcumin promotes hippocampal neurogenesis by activating Wnt/β-catenin signaling pathway to ameliorate cognitive deficits after acute CI.

Topics: Animals; beta Catenin; Brain; Brain Ischemia; Cell Differentiation; Cell Proliferation; Cerebral Infarction; China; Cognition Disorders; Cognitive Dysfunction; Curcumin; Dentate Gyrus; Hippocampus; Male; Memory; Mice; Mice, Inbred C57BL; Neural Stem Cells; Neurogenesis; Neurons; Wnt Signaling Pathway

The antioxidant activity of C.oil in cerebral stroke has been reported earlier. We have attempted here to clarify the mechanisms underlying the neuroprotection against experimental cerebral ischemia by Curcuma oil (C.oil), isolated from the rhizomes of Curcuma longa. C.oil (250 mg/kg i.p.) was given 30 min before focal ischemia in rats caused by occlusion of the middle cerebral artery (1h of occlusion, 24h of reflow). Ischemia, leads to elevation in [Ca(2+)] this sets into motion a cascades of ischemic injury which was attenuated by C.oil. C.oil reduced post-ischemic brain neutrophil infiltration in the ischemic area, controlled tissue NOx levels and the neuronal levels of nitric oxide, peroxynitrite and reactive oxygen species when measured after 24h of reflow. Double immunofluorescence staining analysis and Western immunoblot analysis with C.oil treatment showed that the expression of nitric oxide synthase (NOS) isoforms were decreased significantly compared to the untreated ischemia group. Ischemia is associated with increased in TUNEL (TdT-mediated dUTP nick-end labeling) positive cells in brain sections indicating DNA fragmentation. The C.oil treated group showed a significant decrease in numbers of apoptotic cells compared to the untreated ischemia group, as seen in the flowcytometric analysis of the neurons. Results of immunohistochemistry and Western immunoblot indicate that C.oil suppressed the elevated protein level of Bax, and aided mitochondrial translocation and activation of Bcl-2 by altered mitochondrial membrane potential. It also inhibits the cytosolic release of apoptogenic molecules like cytochrome c, inhibits the activation of caspase-3 and the expression of p53 ultimately inhibiting apoptosis. Our observations suggest that high levels of NO generated by NOS isoforms are partially responsible for exacerbating the neuronal damage induced by MCAo by intraluminal filament.

Topics: Animals; Apoptosis; Blotting, Western; Brain Ischemia; Cerebral Infarction; Curcuma; Cytochrome c Group; DNA Fragmentation; Flow Cytometry; Gene Expression Regulation; In Situ Nick-End Labeling; Male; Mitochondria; Neurons; Nitric Oxide; Nitric Oxide Synthase; Oils, Volatile; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Time Factors