title: N-Acetylcysteine and Ceftriaxone as Preconditioning Strategies in Focal Brain Ischemia: Influence on Glutamate Transporters Expression.
abstract: Glutamate (Glu) plays a key role in excitotoxicity-related injury in cerebral ischemia. In the brain, Glu homeostasis depends on Glu transporters, including the excitatory amino acid transporters and the cysteine/Glu antiporter (xc-). We hypothesized that drugs acting on Glu transporters, such as ceftriaxone (CEF, 200 mg/kg, i.p.) and N-acetylcysteine (NAC, 150 mg/kg, i.p.), administered repeatedly for 5 days before focal cerebral ischemia in rats and induced by a 90-min middle cerebral artery occlusion (MCAO), may induce brain tolerance to ischemia. We compared the effects of these drugs on brain infarct volume, neurological deficits and the mRNA and protein expression of the Glu transporter-1 (GLT-1) and xc- with the effects of ischemic preconditioning and chemical preconditioning using 3-nitropropionic acid. Administration of CEF and NAC significantly reduced infarct size and neurological deficits caused by a 90-min MCAO. These beneficial effects were accompanied by changes in GLT-1 expression caused by a 90-min MCAO at both the mRNA and protein levels in the frontal cortex, hippocampus, and dorsal striatum. Thus, the results of this study suggest that the regulation of GLT-1 and xc- plays a role in the development of cerebral tolerance to ischemia and that this regulation may be a novel approach in the therapy of brain ischemia.
authors: Department of Biochemical Toxicology, Faculty of Pharmacy, Jagiellonian University, Medical College, Medyczna 9, 30-688, Krakow, Poland.
authors: Weronika
authors: W
authors: Krzyzanowska
authors: Department of Biochemical Toxicology, Faculty of Pharmacy, Jagiellonian University, Medical College, Medyczna 9, 30-688, Krakow, Poland. bartosz.pomierny@uj.edu.pl.
authors: Bartosz
authors: B
authors: Pomierny
authors: Department of Biochemical Toxicology, Faculty of Pharmacy, Jagiellonian University, Medical College, Medyczna 9, 30-688, Krakow, Poland.
authors: Boguslawa
authors: B
authors: Budziszewska
authors: Department of Toxicology, Faculty of Pharmacy, Jagiellonian University, Medical College, Medyczna 9, 30-688, Krakow, Poland.
authors: Malgorzata
authors: M
authors: Filip
authors: Department of Neurology, Jagiellonian University, Medical College, Botaniczna 3, 31-503, Krakow, Poland.
authors: Joanna
authors: J
authors: Pera
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology* / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D002443:Ceftriaxone / Q000494:pharmacology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009422:Nervous System Diseases / Q000209:etiology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D027342:Excitatory Amino Acid Transporter 2; D018696:Neuroprotective Agents; D012333:RNA, Messenger; C493395:Slc1a2 protein, rat; D002443:Ceftriaxone; D000111:Acetylcysteine
keywords: Brain ischemia; Brain preconditioning; Ceftriaxone; N-acetylcysteine; Neuroprotection