title: Preconditioning effect of (S)-3,5-dihydroxyphenylglycine on ischemic injury in middle cerebral artery occluded Sprague-Dawley rats.
abstract: Glutamate receptors are the integral cellular components associated with excitotoxicity mechanism induced by the ischemic cascade events. Therefore the glutamate receptors have become the major molecular targets of neuroprotective agents in stroke researches. Recent studies have demonstrated that a Group I metabotropic glutamate receptor agonist, (S)-3,5-dihydroxyphenylglycine ((S)-3,5-DHPG) preconditioning elicits neuroprotection in the hippocampal slice cultures exposed to toxic level of N-methyl-d-aspartate (NMDA). We further investigated the preconditioning effects of (S)-3,5-DHPG on acute ischemic stroke rats. One 10 or 100μM of (S)-3,5-DHPG was administered intrathecally to Sprague-Dawley adult male rats, 2h prior to induction of acute ischemic stroke by middle cerebral artery occlusion (MCAO). After 24h, neurological deficits were evaluated by modified stroke severity scores and grid-walking test. All rats were sacrificed and infarct volumes were determined by 2,3,5-triphenyltetrazolium chloride staining. The serum level of neuron-specific enolase (NSE) of each rat was analyzed by enzyme-linked immunosorbent assay (ELISA). One and 10μM of (S)-3,5-DHPG preconditioning in the stroke rats showed significant improvements in motor impairment (P<0.01), reduction in the infarct volume (P<0.01) and reduction in the NSE serum level (P<0.01) compared to the control stroke rats. We conclude that 1 and 10μM (S)-3,5-DHPG preconditioning induced protective effects against acute ischemic insult in vivo.
authors.affiliation: Institute of Medical Molecular Biotechnology, Universiti Teknologi MARA, 47000 Selangor, Malaysia.
authors.forename: Nik Nasihah
authors.initials: NN
authors.lastname: Nik Ramli
authors.affiliation: Institute of Medical Molecular Biotechnology, Universiti Teknologi MARA, 47000 Selangor, Malaysia.
authors.forename: Nursyazwani
authors.initials: N
authors.lastname: Omar
authors.affiliation: Faculty of Dentistry, Universiti Teknologi MARA, 40450, Shah Alam, Selangor, Malaysia; Brain and Neuroscience Communities of Research, Universiti Teknologi MARA, 40450, Shah Alam, Selangor, Malaysia.
authors.forename: Andrean
authors.initials: A
authors.lastname: Husin
authors.affiliation: Brain Research and Information Network, Centre for Neurocognitive Sciences, Universiti Sains Malaysia, 16150 Kelantan, Malaysia.
authors.forename: Zalina
authors.initials: Z
authors.lastname: Ismail
authors.affiliation: Brain and Neuroscience Communities of Research, Universiti Teknologi MARA, 40450, Shah Alam, Selangor, Malaysia. Electronic address: iisturidza@yahoo.com.
authors.forename: Rosfaiizah
authors.initials: R
authors.lastname: Siran
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D002545:Brain Ischemia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000503:physiopathology / Q000517:prevention & control*; D007278:Injections, Spinal; D008297:Male; D018696:Neuroprotective Agents / Q000737:chemistry / Q000627:therapeutic use*; D010751:Phosphopyruvate Hydratase / Q000097:blood; D017207:Rats, Sprague-Dawley; D012118:Resorcinols / Q000737:chemistry / Q000627:therapeutic use*; D013237:Stereoisomerism
chemical_list: D018696:Neuroprotective Agents; D012118:Resorcinols; C079215:3,5-dihydroxyphenylglycine; D010751:Phosphopyruvate Hydratase; D005998:Glycine
keywords: (S)-3,5-DHPG; Ischemic stroke; Middle cerebral artery occlusion; Preconditioning