title: Neuroprotective effect of ceftriaxone in a rat model of traumatic brain injury.
abstract: Traumatic brain injury (TBI) is a leading cause of mortality and disability in children and young adults worldwide. Neurologic impairment is caused by both immediate brain tissue disruption and post-injury cellular and molecular events that worsen the primary neurologic insult. The β-lactam antibiotic ceftriaxone (CTX) has been reported to induce neuroprotection in animal models of diverse neurologic diseases via up-regulation of GLT-1. However, no studies have addressed the neuroprotective role of CTX in the setting of TBI, and whether the mechanism is involved in the modulation of neuronal autophagy remains totally unclear. The present study was designed to determine the hypothesis that administration of CTX could significantly enhance functional recovery in a rat model of TBI and whether CTX treatment could up-regulate GLT-1 expression and suppress post-TBI neuronal autophagy. The results demonstrated that daily treatment with CTX attenuated TBI-induced brain edema and cognitive function deficits in rats. GLT-1 is down-regulated following TBI and this phenomenon can be reversed by treatment of CTX. In addition, we also found that CTX significantly reduced autophagy marker protein, LC3 II, in hippocampus compared to the TBI group. These results suggest that CTX might provide a new therapeutic strategy for TBI and this protection might be associated with up-regulation of GLT-1 and suppression of neuronal autophagy.
authors.affiliation: Department of Surgery, Hebei Medical University, No. 361 East Zhongshan Road, Shijiazhuang, 050017, People's Republic of China, jzhcuidr2001@163.com.
authors.forename: Changmeng
authors.initials: C
authors.lastname: Cui
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.forename: Junling
authors.initials: J
authors.lastname: Gao
authors.forename: Liqian
authors.initials: L
authors.lastname: Sun
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Wang
authors.forename: Kaijie
authors.initials: K
authors.lastname: Wang
authors.forename: Ran
authors.initials: R
authors.lastname: Li
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Tian
authors.forename: Sixin
authors.initials: S
authors.lastname: Song
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Cui
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002443:Ceftriaxone / Q000494:pharmacology*; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D002443:Ceftriaxone; D027342:Excitatory Amino Acid Transporter 2; D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; C526109:Anxa3 protein, rat; C493395:Slc1a2 protein, rat