Tongqiao Huoxue Decoction (TQHXD) ameliorates ischaemic stroke in rats by promoting glycolysis enhancing neurogenesis and activating BDNF/AKT/CREB signalling pathway.

Tongqiao Huoxue Decoction (TQHXD), a representative traditional prescription for treating vascular blood stasis syndromes of the head and face, has been widely used in the management of ischemic stroke (IS). Our previous studies have demonstrated that TQHXD activates glycolysis and improves energy metabolism, thereby exerting neuroprotective effects. However, the specific mechanisms underlying its neuroprotective action remain unclear. This study aimed to investigate whether TQHXD promotes neurogenesis through activation of the BDNF/AKT/CREB signaling pathway. A middle cerebral artery occlusion (MCAO) model was established in rats via the intraluminal filament method. Neurological function was evaluated using neurological deficit scoring and the adhesive removal test. Infarct volume, brain water content, cerebral blood flow, and histopathological changes were assessed to determine therapeutic efficacy. The effects of TQHXD and its component formulae on glycolysis were examined by Western blotting and Enzyme-Linked Immunosorbent Assay ‌(ELISA). Neurogenesis was assessed by immunohistochemistry and immunofluorescence, and the underlying mechanisms were validated via Western blotting and quantitative polymerase chain reaction (qPCR). Results showed that TQHXD markedly improved pathological changes and promoted functional recovery in ischemic stroke. Additionally, TQHXD enhances glycolytic flux, promotes migration of immature neurons to peri-infarct regions, facilitates neurogenesis, and activates the BDNF/AKT/CREB signaling pathway. Inhibition of glycolytic flux reverses TQHXD's activation of the BDNF/AKT/CREB signaling pathway and neurogenesis effects. In summary, TQHXD promotes endogenous neurogenesis by activating the BDNF/AKT/CREB pathway through glycolytic activation, suggesting its potential as a therapeutic target for ischemic stroke.