Department of Neurology, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, 330006, Jiangxi, China.
Institute of Neuroscience, Nanchang University, Nanchang, 330006, Jiangxi, China.
BMC Neurosci. 2021 Jan 15;22(1):2. doi: 10.1186/s12868-020-00606-z.
Status epilepticus (SE) is a life-threatening neurological disorder. The hippocampus, as an important area of the brain that regulates cognitive function, is usually damaged after SE, and cognitive deficits often result from hippocampal neurons lost after SE. Fyn, a non-receptor Src family of tyrosine kinases, is potentially associated with the onset of seizure. Saracatinib, a Fyn inhibitor, suppresses epileptogenesis and reduces epileptiform spikes. However, whether saracatinib inhibits cognitive deficits after SE is still unknown.
In the present study, a pilocarpine-induced SE mouse model was used to answer this question by using the Morris water maze and normal object recognition behavioral tests.
We found that saracatinib inhibited the loss in cognitive function following SE. Furthermore, we found that the number of hippocampal neurons in the saracatinib treatment group was increased, when compared to the SE group.
These results showed that saracatinib can improve cognitive functions by reducing the loss of hippocampal neurons after SE, suggesting that Fyn dysfunction is involved in cognitive deficits after SE, and that the inhibition of Fyn is a possible treatment to improve cognitive function in SE patients.
癫痫持续状态（SE）是一种危及生命的神经系统疾病。海马作为调节认知功能的重要脑区，通常在 SE 后受损，而 SE 后海马神经元的丢失往往导致认知缺陷。Fyn 是一种非受体Src 家族酪氨酸激酶，可能与癫痫发作的发生有关。Saracatinib 是一种 Fyn 抑制剂，可抑制癫痫发生并减少癫痫样棘波。然而，saracatinib 是否抑制 SE 后认知缺陷仍不清楚。
本研究采用匹鲁卡品诱导的 SE 小鼠模型，通过 Morris 水迷宫和正常物体识别行为测试来回答这个问题。
我们发现 saracatinib 抑制了 SE 后认知功能的丧失。此外，与 SE 组相比，saracatinib 治疗组的海马神经元数量增加。
这些结果表明，saracatinib 可通过减少 SE 后海马神经元的丢失来改善认知功能，提示 Fyn 功能障碍参与 SE 后认知缺陷，抑制 Fyn 可能是改善 SE 患者认知功能的一种治疗方法。
