L‐3‐n‐butylphthalide Promotes Neurogenesis and Neuroplasticity in Cerebral Ischemic Rats

This study investigated whether anticerebral ischemia new drug, l‐3‐n‐butylphthalide (l‐NBP), improved behavioral recovery and enhanced hippocampal neurogenesis after cerebral ischemia in rats.

The middle cerebral artery of rats was blocked for 2 h. The daily oral administrations of 30 mg/kg l‐NBPor vehicle were begun from the second day until the rats were sacrificed. L‐NBPtreatment markedly increased 5‐bromo‐2′‐deoxyuridine (BrdU)‐positive cells in the hippocampal dentate gyrus (DG) of injured hemisphere on day 28 after ischemia. The amount of newborn cells and newly mature neurons was also increased. The expressions of growth‐associated protein‐43 and synaptophysin were significantly elevated in l‐NBP‐treated rats. However, l‐NBPmarkedly reduced the percentage of BrdU⁺/GFAP⁺cells. Additionally, the levels of catalytical subunit of protein kinase A (PKA), protein kinase B (Akt), andcAMPresponse element‐binding protein (CREB) were significantly increased, and the activation of the signal transducer and activation of transcription 3 (STAT3) and the expressions of cleaved caspase‐3 and Bax were obviously inhibited by l‐NBP. Consequently, l‐NBPattenuated the behavioral dysfunction.

It first demonstrates that l‐NBPmay improve the behavioral outcome of cerebral ischemia by promoting neurogenesis and neuroplasticity. Activation ofCREBand Akt and inhibition ofSTAT3 signaling might be involved in.