Effect of Centella asiatica on pathophysiology of mild chronic cerebral hypoperfusion in rats

Abstract

The present study investigated the effect of standardized Centella asiatica extract on cognition and hippocampal pathology of mild chronic cerebral hypoperfusion (CCH) that was induced by permanent right common carotid artery occlusion (RCO) in rats. Sixty-four male Sprague-Dawley rats were randomly divided into four groups of Sham-veh, Sham-C. asiatica, RCO-veh and RCO-C. asiatica, which were further divided into short-term and long-term CCH induction. Oral treatments with 20 mg/kg C. asiatica initiated 24 hours and 12 months after CCH and continued for 14 consecutive days. According to the cognition and histopathological evaluation period, the experiment was divided into 2 sets of either 2 or 12 months of CCH. Results showed that 2-month CCH induced learning flexibility deficit associated with CA1 neuronal damage and internal capsule (IC) astroglia activation. Long-lasting (12 months) mild CCH induced spatial learning, memory and flexibility deficits associated with progressive dorsal hippocampal damage. Treatment with 20 mg/kg of C. asiatica improved learning flexibility deficit after 2 and 12 months of CCH. C. asiatica ameliorated neuronal damage in the dorsal hippocampus at 2 months of CCH when given 24 hours after CCH onset. Treatment with C. asiatica after 12 months of cerebral blood flow reduction improved memory and learning flexibility deficits and was associated with the dentate gyrus neuronal damage reduction. Our finding indicates the therapeutic potential of C. asiatica either when given immediately after ischemic insult or when administered one year after ischemic insult, in a CCH rat model.