Sabinene confers protection against cerebral ischemia in rats: potential roles of antioxidants, anti-inflammatory effects, and astrocyte-neurotrophic support

Abstract

OBJECTIVE: Ischemic stroke is a chronic neurological disorder that causes death and disability worldwide. Studies have demonstrated that extravasations of substrates alter astrocytic and neurotrophic activity through oxidative and inflammatory pathways, with significant implications for the severity of ischemic stroke. Hence, agents with anti-oxidant and anti-inflammatory properties may benefit disease treatment. MATERIALS AND METHODS: We investigated the anti-stroke properties of sabinene, a monoterpene compound with neuroprotective properties, in rats with bilateral common-carotid artery occlusion/reperfusion (BCCAO/R)-induced cerebral ischemia. Male rats, grouped into sham, BCCAO/R, sabinene (2.5, 5 and 10 mg/kg) and rivaroxaban (2.5 mg/kg) cohorts, underwent 30 min of BCCAO and 24 h of reperfusion. The consequences on neurological scores, motor activity and coordination, peripheral glucose, neurochemical enzyme - acetylcholinesterase activity, and oxidative, nitrergic, and inflammatory cytokines in the prefrontal cortex, hippocampus and cerebellum, which are critically affected during ischemic stroke, were characterized. Glial fibrillary acidic protein (GFAP) and brain-derived neurotrophic factor (BDNF), indicative of astrocytic dysfunction and synaptopathy, were investigated in these brain regions. RESULTS: BCCAO/R significantly induced neurological deficits, motor and cognitive impairments, which were reversed by sabinene relative to the BCCAO/R group. Biochemical assays revealed that sabinene increased glutathione, catalase and superoxide dismutase antioxidants in the prefrontal cortex, hippocampus and cerebellum, alongside decreased malondialdehyde and nitrite contents in these brain regions. Sabinene reduced acetylcholinesterase activity in the prefrontal cortex and cerebellum, accompanied by increased BDNF in the three brain regions. BCCAO/R-induced upregulation of GFAP concentrations was most notably reduced in the prefrontal cortex and hippocampus. DISCUSSION: Sabinene protects the brain against BCCAO/R-induced stroke in rats via antioxidants, anti-inflammatory effects, and astrocyte-neurotrophic support.