The effects of P-hydroxycinnamic acid in ameliorating spatial learning and flexibility deficits in rats with chronic cerebral hypoperfusion

Abstract

Cerebral blood reduction resulting in oligemic energy failure and metabolic insufficiency initiates gradual neurodegeneration and cognitive impairments. We investigated the neuroprotective effects of p-hydroxycinnamic acid (pHCA) on neurodegeneration in association with cognitive impairments in rats with chronic cerebral hypoperfusion (CCH). Forty male Sprague-Dawley rats were randomly divided into 4 groups: Sham-veh, 2VO-veh, 2VO-pHCA50 and 2VO-pHCA100. We used modified 2-vessel occlusion (2VO) to induce CCH, and the 2 latter groups were given 50 mg/kg and 100 mg/kg of pHCA after the 2VO operation, respectively, which continued for 3 weeks. The behavioral tests consisted of anxiety-like behavior tested in an elevated plus maze (EPM) and hippocampal-dependent spatial learning and flexibility tested in a Morris water maze (MWM). Brain oxidative status, infarction, vulnerable hippocampus and corpus callosum (CC) white matter degeneration were evaluated. The results showed that modified 2VO induced reversible short-term anxiolytic-like behavior in the EPM (p < 0.05). Brain tissue analysis showed that modified 2VO induced gradual change to brain oxidative status (p > 0.05) with significance infarction, vulnerable hippocampal CA1, CA3, DG and CC degeneration (p < 0.05). These were found along with significant spatial learning and flexibility deficits (p < 0.05). Additionally, 100 mg/kg of pHCA significantly ameliorated the spatial learning and flexibility deficits, which coincided with the significant decreases of infarction volume, CA1, CA3 and CC degeneration (p < 0.05). We conclude that pHCA’s improving effects on spatial learning and flexibility deficits are neuroprotective against oligemic energy failure-induced vulnerable neuronal and white matter degeneration in CCH rats.