DL-3-n-butylphthalide promotes neuroplasticity and motor recovery in stroke rats

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Backgrounds and aims:Racemic l-3-n-butylphthalide (DL-NBP), is able to achieve a functional recovery in animal models of cerebral ischemia, vascular dementia, and Alzheimer's disease. In this study, we investigated the effect of DL-NBP on axonal growth, neurogenesis and behavioral performances in rats with cerebral ischemia.Methods:Focal cerebral ischemia in rats was produced by intracerebral injection of endothelin-1. Starting from postoperative day 7, the experimental rats were administered 70 mg/kg DL-NBP by oral gavage for two weeks. Biotinylated dextran amine (BDA) was injected into the contralateral sensorimotor cortex on day 14 after ischemia to trace the sprouting of corticospinal tract (CST) fibers into the denervated cervical spinal cord. The expressions of Nogo-A, Nogo-R, Rho-A, and ROCK in the perilesional cortex, the expressions of BDA, PSD-95, and vGlut1 in the denervated spinal cord, 5-bromo-20-deoxyuridine (BrdU)/DCX-positive cells in the subventricular zone (SVZ) of the injured hemisphere were detected by immunofluorescence. The rats' behavioral abilities were measured on postoperative days 30–32 in the beam-walking, cylinder and sticky label tests.Results:DL-NBP treatment significantly increased the number and length of crossing CST fibers, enhanced significantly the expression levels of synapse-associated proteins including PSD95 and VGlut-1 in the denervated cervical spinal cord, elevated the number of BrdU+/DCX+ cells in SVZ, and reduced markedly those of Rho-A+, ROCK+, Nogo-A+ and Nogo-R+ cells in perilesional cortex. In addition, DL-NBP improved the behavioral performance of the ischemic rats.Conclusion:DL-NBP enhanced the behavioral recovery after cerebral ischemia in rats, possibly by increasing axonal growth and neurogenesis.HighlightsDL-NBP promoted the behavioral performance after cerebral ischemia in rats.DL-NBP improved the behavioral recovery possibly by increasing neurogenesis, axonal regeneration and synapse formation.The axonal regeneration promoted by dl-NBP may be mediated through the Nogo-A/NgR and RhoA/ROCK pathway.

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