Department of Neurology, Children's Hospital of Soochow University, Suzhou, 215025, Jiangsu Province, China; Department of Pediatrics, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China.
Department of Neurology, Children's Hospital of Soochow University, Suzhou, 215025, Jiangsu Province, China.
Epilepsy Res. 2020 Jul;163:106328. doi: 10.1016/j.eplepsyres.2020.106328. Epub 2020 Apr 9.
Recurrent seizures can cause brain damage and affect the cognitive outcome, particularly in developing children. We aimed to determine the effects of recurrent seizures on the expression of gamma-aminobutyric acid A receptor (GABAR) α1 and γ2 subunit and neurodevelopment in immature rats. The role of the GABAR agonist clonazepam and antagonist/partial agonist flumazenil in seizure-induced brain injury was also studied.
Recurrent seizures (RS) were induced by flurothyl inhalation in immature rats. Clonazepam (CZP) and flumazenil (FMZ) were administered to modulate GABAR subunit expression in different experimental groups. Neurobehavioral changes and GABAR α1 and γ2 subunit expression were studied.
Inhalation of flurothyl for five days triggered RS and caused reflex delay, inability to adapt to new environments in adulthood, and deficits in long-term learning and memory ability in rats. Down-regulation of GABAR α1 and γ2 subunits occurred after seizure onset and persisted for a long time. CZP treatment decreased the expression of GABAR α1 and γ2 subunits and delayed neurodevelopment of the immature rats, whereas FMZ did not show any significant effects.
Changes in GABAR α1 and γ2 subunit expression and neurodevelopment were related to recurrent seizures and administration of CZP. Thus, GABAR α1 and γ2 subunits likely play a significant role in the development of immature rats with RS and provide a novel target for therapeutic intervention.
反复发作的癫痫可能导致脑损伤，并影响认知结果，尤其是在发育中的儿童。本研究旨在确定反复发作的癫痫对发育中大鼠γ-氨基丁酸 A 受体（GABAR）α1和γ2亚基表达和神经发育的影响。还研究了 GABAR 激动剂氯硝西泮和拮抗剂/部分激动剂氟马西尼在癫痫诱导的脑损伤中的作用。
通过氟烷吸入诱导发育中大鼠的反复发作性癫痫。氯硝西泮（CZP）和氟马西尼（FMZ）用于调节不同实验组的 GABAR 亚基表达。研究神经行为变化和 GABARα1和γ2亚基表达。
氟烷吸入 5 天可引发癫痫发作，并导致成年大鼠反射延迟、无法适应新环境以及长期学习和记忆能力受损。癫痫发作后 GABARα1和γ2亚基表达下调，并持续很长时间。CZP 治疗可降低 GABARα1和γ2亚基的表达，并延迟发育中大鼠的神经发育，而 FMZ 则无明显作用。
GABARα1和γ2亚基表达和神经发育的改变与反复发作性癫痫和 CZP 给药有关。因此，GABARα1和γ2亚基可能在具有 RS 的发育中大鼠的发育中起重要作用，并为治疗干预提供了新的靶点。
