期刊
NEUROBIOLOGY OF DISEASE
卷 133, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2019.02.010
关键词
Diisopropyl fluorophosphate; EP2; Albumin; Acetylcholinesterase; Neurodegeneration; Status epilepticus; Cyclooxygenase-2; Organophosphorus; Neuroinflammation
资金
- National Institutes of Health (NIH) [NS097776, UO1 NS058158-08, T32 DA15040, R21 NS101167, U01 AG052460, P30 NS055077]
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.
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