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.
This study was aimed to determine whether imipramine chronic treatment promotes neurogenesis in the dentate gyrus (DG) and interferes with neuronal death in the CA1 subfield of the hippocampus after transient global cerebral ischemia (TGCI) in rats. After TGCI, animals were treated with imipramine (20mg/kg, i.p.) or saline during 14 days. 5-Bromo-2'-deoxyuridine-5'-monophosphate (BrdU) was injected 24h after the last imipramine or saline injection to label proliferating cells. In order to confirm the effect of TGCI on neuronal death and cell proliferation, a group of animals was sacrificed 7 days after TGCI. Neurogenesis and neurodegeneration were evaluated by doublecortin (DCX)-immunohistochemistry and Fluoro-Jade C (FJC)-staining, respectively. The rate of cell proliferation increases 7 days but returns to basal levels 14 days after TGCI. There was a significant increase in the number of FJC-positive neurons in the CA1 of animals 7 and 14 days after TGCI. Chronic imipramine treatment increased cell proliferation in the SGZ of DG and reduced the neurodegeneration in the CA1 of the hippocampus 14 days after TGCI. Immunohistochemistry for DCX detected an increased number of newly generated neurons in the hippocampal DG 14 days after TGCI, which was not affected by imipramine treatment. Further studies are needed to evaluate whether imipramine treatment for longer time would be able to promote survival of newly generated neurons as well as to improve functional recovery after TGCI.
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