OA03.03
Purpose: Studies have underlined the importance of repair mechanisms in the recovery phase of stroke. Neurogenesis in response to brain injury is one of the regeneration processes that, if enhanced, may offer better stroke treatment alternatives. In the present study, we were interested to study whether ginkgo biloba (EGb 761) could protect mice from stroke and enhance neurogenesis.
Methods: EGb 761 was administered to mice for 7 days before surgery for pre-treatment paradigms. In another cohort of mice, EGb 761 was immediately administered 4h after pMCAO and continued for 7 days. For neurogenesis experiments, sham, vehicle, EGb 761 post-treated, and HO1-/- mice were injected with 100μL of BrdU (10mg/mL of conc.) at 4h following surgery and then continually for 7 days.
Results: In the present study, we were interested to study whether EGb 761 could protect mice from permanent middle cerebral artery occlusion (pMCAO) and enhance neurogenesis. EGb 761 pre- and post-treated mice had lower infarct volume and improved motor skills with enhanced proliferation of neuronal stem/progenitor cells (NSPCs) at 24 h and 7 days post-treatment. Netrin-1 and its receptors (DCC and UNC5B) that mediate axonal attraction and repulsion were observed to be over-expressed in NSPCs only, implying that netrin-1 and its receptors might have partly played a role in enhanced neurogenesis. Interestingly, in heme oxygenase 1 knockout mice (HO1-/-), neurogenesis was significantly lower than in vehicle-treated mice at day 7. Furthermore, EGb 761 post-treated mice also demonstrated heme oxygenase 1 (HO1)-activated pathway of phosphorylated glycogen synthase kinase 3-α/β (p-GSK-3 α/β), collapsin response mediator protein 2 (CRMP-2), semaphorin3A (SEMA3A), and Wnt, suggesting probable signaling pathways involved in proliferation, differentiation and migration of NSPCs.
Conclusion: Together, these results propose that EGb 761 not only has antioxidant, neuritogenic and angiogenic properties, but can also augment the repair and regeneration mechanisms following stroke.
Contact: Zahoor Shah, zahoor.shah@itoledo.edu
