DL-3-n-butylphthalide promotes hippocampal neurogenesis and reduces mossy fiber sprouting in chronic temporal lobe epilepsy rats

Abstract

Background A decrease in hippocampal neurogenesis is considered an important cause of cognitive impairment, while changes in mossy fiber sprouting are closely related to development of spontaneous recurrent seizures in chronic temporal lobe epilepsy (TLE). Racemic l-3-n-butylphthalide (DL-NBP) can alleviate cognitive impairment in ischemic stroke and Alzheimer’s disease by promoting neurogenesis. DL-NBP treatment can also improve cognitive function and reduce seizure incidence in chronic epileptic mice. However, the mechanisms of action of DL-NBP remain unclear. The aim of the present study was to examine the effects of DL-NBP on mossy fiber sprouting, hippocampal neurogenesis, spontaneous epileptic seizures, and cognitive functioning in the chronic phase of TLE. Methods Nissl staining was used to evaluate hippocampal injury, while immunofluorescent staining was used to analyze hippocampal neurogenesis. The duration of spontaneous seizures was measured by electroencephalography. The Morris water maze was used to evaluate cognitive function. Timm staining was used to assess mossy fiber sprouting. Results TLE animals showed reduced proliferation of newborn neurons, cognitive dysfunction, and spontaneous seizures. Treatment with DL-NBP after TLE increased the proliferation and survival of newborn neurons in the dentate gyrus, reversed the neural loss in the hippocampus, alleviated cognitive impairments, and decreased mossy fiber sprouting and long-term spontaneous seizure activity. Conclusions We provided pathophysiological and morphological evidence that DL-NBP might be a useful therapeutic for the treatment of TLE.

3-n-Butylphthalide suppresses neuroinflammation through BDNF signaling in postoperative cognitive dysfunction in mice

“…[18][19][20] Numerous investigations have demonstrated that NBP possesses notable neuroprotective properties in cerebral ischemia, potentially because of its capacity to diminish cerebral oedema, thus impeding oxidative stress and diminishing neuronal demise and in ammation. [21][22][23] NBP has also been documented to enhance cognitive function in Alzheimer's disease and cerebral ischemia-reperfusion injury. [24][25][26][27][28] Furthermore, prior research has indicated that NBP ameliorates cognitive function in Alzheimer's disease and cerebral ischemiareperfusion injury.…”