Investigation of Ginkgo biloba extract (EGb 761) promotes neurovascular restoration and axonal remodeling after embolic stroke in rat using magnetic resonance imaging and histopathological analysis
EGb 761 is a standardized natural extract from Ginkgo biloba leaf that has shown neuroprotective effects after ischemic stroke.This study aimed to use magnetic resonance imaging (MRI) to noninvasively evaluate whether EGb 761 promotes neurovascular restoration and axonal remodeling in a rat model of focal cerebral ischemia.Male Sprague-Dawley rats were subjected to permanent right middle cerebral artery occlusion (MCAO) and treated with EGb 761 (60 mg/kg) or saline intragastrically once daily for 15 days starting 6 h after MCAO.Functional recovery was analyzed using beam walking test.Multiparametric MRI was applied to examine the alterations of gray-white structures,intracranial vessels,cerebral perfusion and axonal integrity,and followed with histological studies.Furthermore,the protein expression of axonal remodeling related signaling pathways including protein kinase B (AKT)/ glycogen synthase kinase-3β (GSK-3β)/ collapsin response mediator protein 2 (CRMP2) and NogoA/NgR were detected by Western blotting analysis.Multi-parametric MRI demonstrated that EGb 761 significantly reduced infarct volume,alleviated gray and white matter damage,and enhanced collateral circulation,cerebral perfusion and axonal remodeling.Histological examinations supported the MRI results.EGb 761 treatment facilitated behavioral recovery and amplified endogenous neurogenesis.Notably,treatment with EGb 761 significantly increased the levels of p-AKT,p-GSK-3β and decreased the expression of p-CRMP2.In addition,EGb 761 treatment upregulated the expression of growth associated protein 43 (GAP-43) and suppressed the activation of axonal growth inhibitory molecules NogoA and NgR.These findings indicated that EGb 761 enhanced neurovascular restoration,amplified endogenous neurogenesis and promoted axonal regeneration,which in concert may contribute to gray-white matter reorganization and functional outcome after stroke.
School of Traditional Chinese Medicine, Capital Medical University, Beijing,100069, China;Beijing Ke Department of Pharmacology, Beijing University of Chinese Medicine, Beijing,100102, China College of Professional and Continuing Education, The Hong Kong Polytechnic University, Hung Hom, Ho Beijing Key Lab of TCM Collateral Disease Theory Research, Beijing, 100069,China Medical Imaging laboratory of Core Facility Center, Capital Medical University, Beijing, 100069, Chi