Objective: L-3-n-butylphthalide (L-NBP) has been shown to have neuroprotective effects on cerebral ischemic, vascular dementia and amyloid-beta-induced animal models by inhibiting oxidative injury and neuronal apoptosis. Microglia activation and polarization contributes to neuronal damage in stroke. The aim of this study was to investigate the protective effect of NBP on brain damage and sensorimotor function in mice subjected to cerebral ischemia, as well as the immune modulatory effects of L-NBP on sensorimotor function and microglia activation in ischemic brain tissue.
Methods: Male C57Bl/6 mice received sham surgery or transient occlusion of middle cerebral artery (45 min) and L-NBP were administered by intravenous injection at different dosage (7 mg/kg/day, 14 mg/kg/day, 28 mg/kg/day) or vehicle for 3 days. Cerebral infarction volume were determined by TTC staining. Sensorimotor function were assessed by the tape adhesion test and beam walk balance test. The expressions of proteins associated with microglia markekrs were assessed by immunoinfluence and western blot.
Results: Our results showed that L-NBP at three dosages decreased cerebral infarction size and brain edema after MCAO. L-NBP treatment at middle and high dosage significantly suppressed the touch time and romoval time in the tape adhesion test. And L-NBP treatment at middle and high dosage also decreased the score in the balance beam test. In addition, ischemia induced microglia activation in the brain. L-NBP treatment at middle and high dosage significantly suppressed the expression of M1 microglia markers iNOS but not CD11b. At the meantime, L-NBP treatment increased the expression of M2 microglia markers CD206 but not Arg1.
Conclusion: These results suggested that L-NBP might be a promising candidate in reversing the progress of stroke by inhibiting M1 microglia activation.