Effect of berberine on the hippocampal structure, biochemical factors, memory, and blood–brain barrier in rat model of transient global cerebral ischemia

Abstract Global cerebral ischemia (GCI) results in damage to the neurons and leads to cognitive impairments. Berberine (BBR) is known for its neuroprotective qualities. This study aimed to investigate the effects of BBR on memory, Blood–brain barrier (BBB) permeability, biochemical factors, and neuronal structure. Sixty‐three adult male Wistar rats were divided randomly into Sham (21), GCI (21), and GCI + BBR (21) groups. The GCI + BBR group received 50 mg/kg of BBR for 7 days before and 6 h after 20 min of GCI induction. After 24 h, assessments included hippocampal neuronal structure, catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GPX) levels, memory performance, and BBB permeability. The GCI + BBR group reduced volume loss in the CA1 and its sublayers (oriens, pyramidal, and radiatum) compared to the GCI group ( p < 0.0001, p < 0.001, p < 0.01 and p < 0.001, respectively). Additionally, the GCI + BBR group showed higher pyramidal neuron density ( p < 0.0001) and number ( p < 0.0001) compared to the GCI group. BBR also decreased MDA levels ( p < 0.0001) and increased CAT activity ( p < 0.0001) in the GCI + BBR group compared to the GCI group, with GPX and SOD activity approaching Sham levels ( p < 0.0001, both). BBR demonstrated significant improvements in short and long‐term memory compared to the GCI group ( p < 0.01, p < 0.0001, respectively). Furthermore, BBB permeability in the GCI + BBR group was significantly reduced compared to the GCI group ( p < 0.0001). These findings demonstrated BBR's potential to protect the neurons in the CA1 and BBB structures, enhance antioxidant activity, and alleviate GCI‐induced memory impairments.