Neuroprotective Effects of Curcumin Against Transient Global Ischemia are Dose and Area Dependent

Background: Ischemic brain injury is among the most common causes of death and disability in humans worldwide. Recent findings suggest that neural precursors in the adult mammalian brain can be a therapeutic target in ischemic brain injuries. Curcumin stimulates neurogenesis and reduces oxidative stress in the brain. Objectives: The present study compared the neuroprotective effects of different concentrations of curcumin in various regions of the brain in a rat model of transient global ischemia (TGI). Materials and Methods: Forty-eight adult male Wistar rats were randomly chosen as control, sham (animals only underwent TGI), treatment (100 and 300 mg/kg curcumin following TGI), and vehicle groups. The animals underwent global ischemia imposed by a 20 minute ligation of the bilateral common carotid arteries. Cell death and apoptosis in different areas of brain were evaluated after 3 or 4 weeks by Nissl staining and TUNEL assay respectively. Results: The number of dark neurons and apoptotic cells significantly increased after TGI. The number of TUNEL-positive cells after TGI was significantly higher in the temporal neocortex than in different regions within the hippocampus. Treatment with curcumin at a high dose reduced the numbers of dark neurons and apoptotic cells. Lower concentrations of curcumin showed a neuroprotective effect in the neocortex, whereas higher doses prevented cell death and apoptosis in the neocortex and in different regions of the hippocampus. Conclusions: Regional differences were evident with respect to the neuroprotective effects of curcumin in the temporal cortex and in the different parts of hippocampus following TGI. Further studies are needed to explore the mechanisms underlying these regional differences.