title: Pharmacological induction of ischemic tolerance in hippocampal slices by sarcosine preconditioning.
abstract: Brain ischemic tolerance is a protective mechanism induced by a preconditioning stimulus, which prepare the tissue against harmful insults. Preconditioning with N-methyl-d-aspartate (NMDA) agonists induces brain tolerance and protects it against glutamate excitotoxicity. Recently, the glycine transporters type 1 (GlyT-1) have been shown to potentiate glutamate neurotransmission through NMDA receptors suggesting an alternative strategy to protect against glutamate excitotoxicity. Here, we evaluated the preconditioning effect of sarcosine pre-treatment, a GlyT-1 inhibitor, in rat hippocampal slices exposed to ischemic insult. Sarcosine (300 mg/kg per day, i.p.) was administered during seven consecutive days before induction of ischemia in hippocampus by oxygen/glucose deprivation (OGD). To access the damage caused by an ischemic insult, we evaluated cells viability, glutamate release, nitric oxide (NO) production, lactate dehydrogenase (LDH) levels, production of reactive oxygen species (ROS), and antioxidant enzymes as well as the impact of oxidative stress in the tissue. We observed that sarcosine reduced cell death in hippocampus submitted to OGD, which was confirmed by reduction on LDH levels in the supernatant. Cell death, glutamate release, LDH levels and NO production were reduced in sarcosine hippocampal slices submitted to OGD when compared to OGD controls (without sarcosine). ROS production was reduced in sarcosine hippocampal slices exposed to OGD, although no changes were found in antioxidant enzymes activities. This study demonstrates that preconditioning with sarcosine induces ischemic tolerance in rat hippocampal slices submitted to OGD.
authors: Laboratório de Neurociências, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Alfredo Balena 190, 30130-100 Belo Horizonte-MG, Brazil. mauroxavier@ufmg.br
authors: Mauro Cunha Xavier
authors: MC
authors: Pinto
authors: Flávio Afonso Gonçalves
authors: FA
authors: Mourão
authors: Nancy Scardua
authors: NS
authors: Binda
authors: Hércules Ribeiro
authors: HR
authors: Leite
authors: Marcus Vinícius
authors: MV
authors: Gomez
authors: Andre Ricardo
authors: AR
authors: Massensini
authors: Renato Santiago
authors: RS
authors: Gomez
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000172:deficiency; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D009924:Organ Culture Techniques; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012521:Sarcosine / Q000494:pharmacology*
chemical_list: D005947:Glucose; D010100:Oxygen; D012521:Sarcosine