title: Minocycline inhibits brain inflammation and attenuates spontaneous recurrent seizures following pilocarpine-induced status epilepticus.
abstract: Mounting evidence suggests that brain inflammation mediated by glial cells may contribute to epileptogenesis. Minocycline is a second-generation tetracycline and has potent antiinflammatory effects independent of its antimicrobial action. The present study aimed to investigate whether minocycline could exert antiepileptogenic effects in a rat lithium-pilocarpine model of temporal lobe epilepsy. The temporal patterns of microglial and astrocytic activation were examined in the hippocampal CA1 and the adjacent cortex following pilocarpine-induced status epilepticus (SE). These findings displayed that SE caused acute and persistent activation of microglia and astrocytes. Based on these findings, Minocycline was administered once daily at 45 mg/kg for 14 days following SE. Six weeks after termination of minocycline treatment, spontaneous recurrent seizures (SRS) were recorded by continuous video monitoring. Minocycline inhibited the SE-induced microglial activation and the increased production of interleukin-1β and tumor necrosis factor-α in the hippocampal CA1 and the adjacent cortex, without affecting astrocytic activation. In addition, Minocycline prevented the SE-induced neuronal loss in the brain regions examined. Moreover, minocycline significantly reduced the frequency, duration, and severity of SRS during the two weeks monitoring period. These results demonstrated that minocycline could mitigate SE-induced brain inflammation and might exert disease-modifying effects in an animal model of temporal lobe epilepsy. These findings offer new insights into deciphering the molecular mechanisms of epileptogenesis and exploring a novel therapeutic strategy for prevention of epilepsy.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurology, Chongqing, China.
authors.forename: N
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurology, Chongqing, China.
authors.forename: X
authors.initials: X
authors.lastname: Mi
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurology, Chongqing, China.
authors.forename: B
authors.initials: B
authors.lastname: Gao
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurology, Chongqing, China.
authors.forename: J
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurology, Chongqing, China.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurology, Chongqing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurology, Chongqing, China. Electronic address: xfyp@163.com.
authors.forename: X
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D000927:Anticonvulsants / Q000008:administration & dosage*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004569:Electroencephalography; D004660:Encephalitis / Q000517:prevention & control*; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control*; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008911:Minocycline / Q000008:administration & dosage*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D010862:Pilocarpine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced; D013226:Status Epilepticus / Q000139:chemically induced
chemical_list: D000893:Anti-Inflammatory Agents; D000927:Anticonvulsants; D010862:Pilocarpine; D008911:Minocycline
keywords: astrocytes; cytokine; epileptogenesis; microglia; minocycline