Thesis (Ph.D.)--Chulalongkorn University, 2015

Oxidation, inflammation, and apoptosis are three critical factors for the pathogenic mechanism of cerebral ischemia/reperfusion (I/R) damage. Curcumin has been elucidated to exhibit substantial biological properties via anti-oxidation, anti-inflammation and anti-apoptosis effects, however, its molecular mechanism against cerebral I/R injury remains unclear. To investigate the effects of curcumin on cerebral I/R injury associated with water content, infarction volume, blood-brain barrier (BBB) disruption and the expression of ICAM-1, MMP-9, NF-kappa-B, caspases-3, and Nrf2. The middle cerebral artery occlusion (MCAO, 1- hour occlusion and 24-hour reperfusion) was performed in male Wistar rats as representing cerebral I/R injury model. In MCAO+CUR group, rats were received curcumin administration (300 mg/kg BW, ip.) at 30-min after occlusion. The same operated procedures were performed in SHAM rats without MCAO occlusion. At 24-hour post-operation, all of these parameters including neurological deficit scores, BBB disruption, water content, and infarction volume were determined. Brain tissue ICAM-1, MMP-9, NF-kappa-B, caspases-3, and Nrf2 were assayed by immunohistochemistry. Compared with SHAM group, the BBB disruption, neurological deficit scores, brain water content and infarction volume were severely demonstrated in MCAO group. ICAM-1, MMP-9, NF-kappa-B and caspases-3 were enhanced in MCAO group. However, in MCAO+CUR group, the upregulated Nrf2, an anti-oxidation related protein, collaborating with the decline of other biomarkers were significantly observed. The protective effects of curcumin against cerebral I/R injury were attributed to its anti-oxidation, anti-inflammation and anti-apoptosis which were involved in the up-regulation of Nrf2 and the down-regulation of ICAM-1, MMP-9, NF-kappa-B and caspases-3.