title: Reactive astrocytes contribute to increased epileptic susceptibility induced by subthreshold dose of pilocarpine.
abstract: Seizures may influence epileptogenesis, but it is not yet clearly established whether subthreshold stimulations that are not sufficient to induce visible behavioral seizures change epileptic susceptibility, and the possible underlying mechanisms have not been completely understood. We assessed the susceptibility to epilepsy after subthreshold dose of pilocarpine, as well as glial fibrillary acidic protein (GFAP) expression using immunohistochemistry. An increase in the susceptibility to pentylenetetrazole (PTZ)-induced seizures was observed in rats previously subjected to subthreshold dose of pilocarpine. The immunoreactivity of GFAP was also increased, indicating that astrocytes became reactive in some brain subfields. The increased epileptic susceptibility was significantly reduced by L-alpha-aminoadipic acid (L-AAA), an inhibitor of astrocytic function. Our results suggest that subthreshold stimulation may increase the susceptibility to subsequent development of epilepsy, and reactive astrocytes might be an important contributor to this process. Adequate inhibition of astrocytic function may be a potential preventive approach against epileptogenesis.
authors.affiliation: Radiation Medical Institute, Shandong Academy of Medical Sciences, Jinan 250062, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: Shi-Hong
authors.initials: SH
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Feng
authors.forename: Kai
authors.initials: K
authors.lastname: Zhong
authors.forename: Lei-Xiang
authors.initials: LX
authors.lastname: Yang
authors.forename: Hong-Liu
authors.initials: HL
authors.lastname: Sun
authors.forename: Shu-Ping
authors.initials: SP
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.forename: Chao-Yun
authors.initials: CY
authors.lastname: Wang
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Pan
mesh_terms: D015074:2-Aminoadipic Acid / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004827:Epilepsy / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D018721:Muscarinic Agonists / Q000633:toxicity*; D010862:Pilocarpine / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D018691:Excitatory Amino Acid Antagonists; D005904:Glial Fibrillary Acidic Protein; D018721:Muscarinic Agonists; D010862:Pilocarpine; D015074:2-Aminoadipic Acid