Title:Selective Modulator of Cannabinoid Receptor Type 2 Reduces Memory Impairment and Infarct Size During Cerebral Hypoperfusion and Vascular Dementia
VOLUME: 13 ISSUE: 4
Author(s):Shalini Jayant and Bhupesh Sharma
Affiliation:Department of Pharmacology, Amity Institute of Pharmacy, Amity University Uttar Pradesh, A-Block, Ground Floor, Sector-125, Noida – 201303, Uttar Pradesh, India; And CNS and CVS Pharmacology, Conscience Research, Pocket F-233, B, Dilshad Garden, Delhi-110095 India.
Keywords:2, 3, 5-triphenylterazolium chloride staining, vascular occlusion, 1-phenylisatin, brain damage, brain edema, synaptic
plasticity, brain cholinergic activity, mitochondrial dysfunction.
Abstract:Vascular dementia is the highly devastating neurodegenerative disorder after Alzheimer’s
disease (AD) and mainly found in aged people but the effectual therapeutic target is still not there.
Chronic cerebral hypoperfusion (CCH) has been broadly found in vascular dementia (VaD) patients.
CCH is thought to link with neurodegenerative disorders and their subsequent cognitive deteriorate
on. This study has been framed to examine the role of a selective agonist of cannabinoid receptor
type 2(CB2); 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 dysfunction (complexes I, II, IV) with a significant enhancement
in cholinergic activity- AChE and brain infarct size2,3,5-triphenylterazolium chloride staining (TTC
staining). Animals treated with 2VO have also demonstrated a considerable augmentation in brain
edema (water content). Oral administration of 1-phenylisatin has significantly recuperated 2VO induced
impairment in learning-memory, an increase in TBARS, GSH, CAT, SOD, mitochondrial activity
with a significant reduction in AChE activity and brain damage. Administration of 1-
phenylisatin has also reported recovering 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 of cannabinoid receptor may provide benefits in CCH as cognitive impairment
and VaD. Therefore, selective agonists of CB2 receptors may be a potential research target
for the alleviation of VaD.
