A rat model of organophosphate-induced status epilepticus and the beneficial effects of EP2 receptor inhibition

NEUROBIOLOGY OF DISEASE

卷:133

Review

Rojas, Asheebo¹  Ganesh, Thota¹  Wang, Wenyi¹  Wang, Jennifer¹  Dingledine, Raymond¹ 

[1] Emory Univ, Dept Pharmacol, 1510 Clifton Rd NE, Atlanta, GA 30322 USA

关键词: Diisopropyl fluorophosphate;    EP2;    Albumin;    Acetylcholinesterase;    Neurodegeneration;    Status epilepticus;    Cyclooxygenase-2;    Organophosphorus;    Neuroinflammation;   

DOI  :  10.1016/j.nbd.2019.02.010

来源: Elsevier

【 摘 要 】

This review describes an adult rat model of status epilepticus (SE) induced by diisopropyl fluorophosphate (DFP), and the beneficial outcomes of transient inhibition of the prostaglandin-E-2 receptor EP2 with a small molecule antagonist, delayed by 2-4 h after SE onset. Administration of six doses of the selective EP2 antagonist TG6-10-1 over a 2-3 day period accelerates functional recovery, attenuates hippocampal neurodegeneration, neuroinflammation, gliosis and blood-brain barrier leakage, and prevents long-term cognitive deficits without blocking SE itself or altering acute seizure characteristics. This work has provided important information regarding organophosphate-induced seizure related pathologies in adults and revealed the effectiveness of delayed EP2 inhibition to combat these pathologies.