Selective modulator of cannabinoid receptor type 2 (CB2) against biochemical alterations and brain damage in chronic cerebral hypoperfusion induced vascular dementia

Abstract

Vascular dementia is the second most common cause of cognitive decline in aged people but the effectual therapeutic target is still missing. Chronic cerebral hypoperfusion (CCH) has been widely found in vascular dementia (VaD) patients. CCH is thought to link with neurodegenerative disorders and their subsequent cognitive impairment. The present study has been framed to investigate the role of selective agonist of CB2 receptor (1-phenylisatin) in CCH induced VaD. Permanent bilateral common carotid arteries ligation or two vessels occlusion (2VO) technique was used to induce CCH in rats. 2VO animals have shown significant impairment in learning-memory (Morris water maze) and in executive functioning (Attentional set shifting test). These animals have shown a considerable reduction in brain oxidative stress (thiobarbituric reactive acid substance-TBARS; glutathione-GSH; catalase-CAT and superoxide dismutase-SOD), mitochondrial complex activity (complexes I, II, IV) with the enhancement in cholinergic activity- AChE and brain infarct size (TTC staining). These animals have also shown a considerable increase in brain edema (water content). Oral administration of 1-phenylisatin has significantly recuperated 2VO induced impairment in learning-memory, increase in TBARS, GSH, CAT, SOD, mitochondrial activity with a significant reduction in AChE activity and brain damage. Administration of 1-phenylisatin has also been reported to recover brain edema in these animals. These results indicate that 2VO induced CCH in rats, which was attenuated with the treatment of 1-phenylisatin. Hence, it may be suggested that modulation in cannabinoid receptor may provide benefits in CCH as cognitive impairment and VaD. Therefore, pharmacological positive modulation of CB2 receptors may be a potential research target for alleviation of VaD.