Protective Effects of Cannabidiol Against Hippocampal Cell Death and Cognitive Impairment Induced by Bilateral Common Carotid Artery Occlusion in Mice

Abstract

The present study investigated whether cannabidiol (CBD), a major non-psychoactive constituent of marijuana, protects against hippocampal neurodegeneration and cognitive deficits induced by brain ischemia in adult mice. Male Swiss mice were subjected to a 17 min of bilateral common carotid artery occlusion (BCCAO) and tested in the Morris water maze 7 days later. CBD (3, 10, and 30 mg/kg) was administered 30 min before and 3, 24, and 48 h after BCCAO. After behavioral testing, the brains were removed and processed to evaluate hippocampal cell survival and degeneration using Nissl staining and FluoroJade C histochemistry, respectively. Astroglial response was examined using immunohistochemistry for glial fibrillary acidic protein (GFAP). CBD (3-30 mg/kg) improved spatial learning performance in BCCAO mice. The Nissl and FJC staining results showed a decrease in hippocampal neurodegeneration after CBD (10 and 30 mg/kg) treatment. GFAP immunoreactivity was also decreased in ischemic mice treated with CBD (30 mg/kg). These findings suggest a protective effect of CBD on neuronal death induced by ischemia and indicate that CBD might exert beneficial therapeutic effects in brain ischemia. The mechanisms that underlie the neuroprotective effects of CBD in BCCAO mice might involve the inhibition of reactive astrogliosis.

Influence of single and repeated cannabidiol administration on emotional behavior and markers of cell proliferation and neurogenesis in non-stressed mice

“…The behavioral data are presented as means ± SEM. The immunohistochemical data were analyzed using the generalized linear model with a Poisson distribution to model the count data, i.e., number of cells (Schiavon et al, 2014). Values of p b 0.05 were considered statistically significant.…”

“…The meaning of this finding is still unknown. Imipramine and CBD presented protective effects under of different animal models of neurodegenerative conditions, such as brain ischemia (Pazos et al, 2012;Schiavon et al, 2010;Schiavon et al, 2014), Alzheimer's disease (Cheng et al, 2014), Parkinson's disease (LastresBecker et al, 2005), and schizophrenia (Gomes et al, 2015). The proneurogenic activity of CBD observed in the SVZ, therefore, might be related to its reparative and/or neuroprotective effects.…”

Effect of Melatonin and Resveratrol against Memory Impairment and Hippocampal Damage in a Rat Model of Vascular Dementia

“…Chronic cerebral hypoperfusion can be induced in rodents by causing permanent bilateral common carotid artery occlusion (BCCAO) that results in cognitive dysfunction and hippocampal injury [8][9][10][11] . Moreover, chronic cerebral hypoperfusion-induced hippocampal damage and cognitive dysfunction are also associated with the activation of proinflammatory cytokines such as interleukin (IL)-1β, and tumor necrosis factor (TNF)-α [12][13][14][15] .…”

Cannabidiol provides viable treatment opportunity for multiple neurological pathologies of autism spectrum disorder

“…CBD administration was found to rescue reserpine-induced motor and cognitive impairments, normalize MK-801-induced social deficits and hyperactivity, and attenuate THC-induced reduction in social interaction in rats [37][38][39][40]. Acute CBD treatment also protected against hippocampal cell death and improved cognition in mouse models of ischemia and cerebral malaria [41,42]. CBD can also reduce learned fear by decreasing fear expression, disrupting memory reconsolidation, and enhancing extinction in contextual fear memory paradigm as shown in a study involving mice [43].…”