Abstract
BackgroundA 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.MethodsNissl 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.ResultsTLE 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.ConclusionsWe provided pathophysiological and morphological evidence that DL-NBP might be a useful therapeutic for the treatment of TLE.
Highlights
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)
DL‐NBP treatment promotes neurogenesis in the dentate gyrus Immunofluorescent staining of DCX-positive neuroblasts was performed to examine whether DL-NBP treatment could regulate neurogenesis in the dentate gyrus (DG) (Fig. 1)
These data suggest that DL-NBP treatment attenuated neuronal loss caused by kainic acid (KA)-induced epilepsy
Summary
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). 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. Recent studies have shown that DLNBP improves cognitive function in traumatic brain injury, ischemic stroke, and Alzheimer’s disease, likely by reducing neural loss and promoting neuronal regeneration [5,6,7,8]. One study confirmed that DL-NBP could improve cognitive function and alleviate seizure severity in mouse with chronic epilepsy [9] They proved that DL-NBP treatment reduced the loss of hippocampal neurons in mice with chronic epilepsy. The effects of DL-NBP treatment on hippocampal neurogenesis and the mechanisms of reducing seizure incidence by DL-NBP treatment in TLE model are unknown
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