Seker Fatma Burcu, Yorulmaz Hatice, Kaptan Engin, Caglayan Berrak, Oztas Baria
Nutr Neurosci. 2016;19(2):55-62. doi: 10.1179/1476830514Y.0000000154. Epub 2014 Sep 15.
Folic acid (FA) is physiologically important in mammals and is a common vitamin supplement used during pregnancy and lactation. Numerous studies have reported that FA significantly improves endothelial function. The blood-brain barrier (BBB) plays an important role in maintaining the microenvironment required for neuronal function, but its unique structure is damaged by epileptic seizures. The aim of this study was to evaluate the potential protective role of FA on BBB leakage, as well as on the reactive astrogliosis in pregnant rats and their prepubertal offspring during pentylenetetrazole (PTZ)-induced epileptic seizure.
Pregnant rats were treated with FA (5 mg/kg) and PTZ on gestational days 0-19 and 19, respectively. The pups were treated with PTZ at puberty. Evans blue was used to evaluate BBB integrity. Reactive astrogliosis was defined using immunohistochemical analysis for glial fibrillary acidic protein (GFAP). Mean arterial blood pressure (MABP) was measured at the femoral artery.
A moderate decrease in BBB leakage was observed in FA-treated pregnant and prepubertal animals (P < 0.05). MABP was decreased significantly in pregnant rats (P < 0.05). The epilepsy-induced increase in MABP was less prominent in pregnant animals (P < 0.05). GFAP intensity decreased in PTZ-treated pregnant animals (P < 0.01) and FA-treated prepubertal rats.
Our findings suggest that FA, which is used as a maternal vitamin to promote normal fetus development, may be beneficial against seizure-induced neuronal damage by decreasing BBB leakage and reactive astrogliosis in pregnant and prepubertal rats.
叶酸（FA）在哺乳动物生理过程中具有重要意义，是孕期和哺乳期常用的维生素补充剂。大量研究报道，FA可显著改善内皮功能。血脑屏障（BBB）在维持神经元功能所需的微环境中起重要作用，但其独特结构会因癫痫发作而受损。本研究旨在评估FA对戊四氮（PTZ）诱导的癫痫发作期间孕鼠及其青春期前后代血脑屏障渗漏以及反应性星形胶质细胞增生的潜在保护作用。
分别在妊娠第0 - 19天和第19天对孕鼠给予FA（5 mg/kg）和PTZ。幼崽在青春期接受PTZ处理。使用伊文思蓝评估血脑屏障完整性。通过胶质纤维酸性蛋白（GFAP）免疫组化分析定义反应性星形胶质细胞增生。在股动脉测量平均动脉血压（MABP）。
在接受FA处理的孕鼠和青春期前动物中观察到血脑屏障渗漏适度降低（P < 0.05）。孕鼠的MABP显著降低（P < 0.05）。癫痫诱导的MABP升高在孕鼠中不太明显（P < 0.05）。PTZ处理的孕鼠（P < 0.01）和FA处理的青春期前大鼠中GFAP强度降低。
我们的研究结果表明，作为母体维生素用于促进胎儿正常发育的FA，可能通过减少孕鼠和青春期前大鼠的血脑屏障渗漏及反应性星形胶质细胞增生，对癫痫诱导的神经元损伤具有保护作用。
