Cannabidiol improves metabolic dysfunction in middle-aged diabetic rats submitted to a chronic cerebral hypoperfusion.

Cannabidiol (CBD), a compound obtained from Cannabis sativa, has wide range of therapeutic properties, including mitigation of diabetes and neurodegeneration. Cerebral ischemia and consequent learning disabilities are aggravated in elderly diabetic subjects. However, there are no studies showing the effect of CBD treatment in elderly diabetes patients suffering cerebral ischemia. The present work tested the hypothesis that CBD treatment improves metabolic dysfunctions in middle-aged diabetic rats submitted to chronic cerebral hypoperfusion. In this work, 350-day-old male Wistar streptozotocin-induced diabetic rats were used. To induce cerebral ischemia was used a chronic cerebral hypoperfusion (CCH), surgically, via the four-vessel occlusion/internal carotid artery (4-VO/ICA). Four diabetic groups were established: Non-CCH Treated Diabetic (DNT), CCH Treated Diabetic (DCT), Non-CCH Vehicle Diabetic (DNV), and CCH Vehicle Diabetic (DCV). Vehicle groups were not treated with CBD. The animals were treated during 30 days with 10 mg CBD/Kg bw/day. After treatment, the animals were euthanized, and blood levels of glucose, insulin, total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides, fructosamine, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were evaluated. DCT group presented reduction of hyperglycemia and an increase of insulinemia. Also was observed lower fructosamine, LDL, HDL, triglycerides and total cholesterol levels. AST and ALT concentration were reduced in CBD treated groups. CBD may be used as therapeutic tool to protect metabolism against injuries from diabetes aggravated by cerebral ischemia.

Effects of Cannabidiol on Diabetes Outcomes and Chronic Cerebral Hypoperfusion Comorbidities in Middle-Aged Rats.

Diabetes and aging are risk factors for cognitive impairments after chronic cerebral hypoperfusion (CCH). Cannabidiol (CBD) is a phytocannabinoid present in the Cannabis sativa plant. It has beneficial effects on both cerebral ischemic diseases and diabetes. We have recently reported that diabetes interacted synergistically with aging to increase neuroinflammation and memory deficits in rats subjected to CCH. The present study investigated whether CBD would alleviate cognitive decline and affect markers of inflammation and neuroplasticity in the hippocampus in middle-aged diabetic rats submitted to CCH. Diabetes was induced in middle-aged rats (14 months old) by intravenous streptozotocin (SZT) administration. Thirty days later, the diabetic animals were subjected to sham or CCH surgeries and treated with CBD (10 mg/kg, once a day) during 30 days. Diabetes exacerbated cognitive deficits induced by CCH in middle-aged rats. Repeated CBD treatment decreased body weight in both sham- and CCH-operated animals. Cannabidiol improved memory performance and reduced hippocampal levels of inflammation markers (inducible nitric oxide synthase, ionized calcium-binding adapter molecule 1, glial fibrillary acidic protein, and arginase 1). Cannabidiol attenuated the decrease in hippocampal levels of brain-derived neurotrophic factor induced by CCH in diabetic animals, but it did not affect the levels of neuroplasticity markers (growth-associated protein-43 and synaptophysin) in middle-aged diabetic rats. These results suggest that the neuroprotective effects of CBD in middle-aged diabetic rats subjected to CCH are related to a reduction in neuroinflammation. However, they seemed to occur independently of hippocampal neuroplasticity changes.

4-hydroxy-3-methoxy-acetophenone-mediated long-lasting memory recovery, hippocampal neuroprotection, and reduction of glial cell activation after transient global cerebral ischemia in rats.

4-Hydroxy-3-methoxy-acetophenone (apocynin) is a naturally occurring methoxy-substitute catechol that is isolated from the roots of Apocynin cannabinum (Canadian hemp) and Picrorhiza kurroa (Scrophulariaceae). It has been previously shown to have antioxidant and neuroprotective properties in several models of neurodegenerative disease, including cerebral ischemia. The present study investigates the effects of apocynin on transient global cerebral ischemia (TGCI)-induced retrograde memory deficits in rats. The protective effects of apocynin on neurodegeneration and the glial response to TGCI are also evaluated. Rats received a single intraperitoneal injection of apocynin (5 mg/kg) 30 min before TGCI and were tested 7, 14, and 21 days later in the eight-arm aversive radial maze (AvRM). After behavioral testing, the hippocampi were removed for histological evaluation. The present results confirm that TGCI causes memory impairment in the AvRM and that apocynin prevents these memory deficits and attenuates hippocampal neuronal death in a sustained way. Apocynin also decreases OX-42 and glial fibrillary acidic protein immunoreactivity induced by TGCI. These findings support the potential role of apocynin in preventing neurodegeneration and cognitive impairments following TGCI in rats. The long-term protective effects of apocynin may involve inhibition of the glial response.