title: The acoustic startle reflex in Sprague-Dawley rats is altered by permanent middle cerebral artery occlusion.
abstract: The startle reflex is an unconditioned, quantifiable behavior used to study sensory modalities. We examined whether the acoustic startle reflex (ASR) was sensitive to lesions induced by focal cerebral ischemia. Sprague-Dawley rats were pre-screened for startle reflex responses 3-6 days prior to surgery and there were no differences in mean startle amplitude across groups. Animals were subjected to permanent middle cerebral artery occlusion (pMCAo) or a sham surgical procedure. Twenty-four hours later rats were evaluated for ASR prior to sacrifice. Infarct volumes were subsequently determined by quantitative image analysis of 2,3,5-triphenyltetrazolium chloride-stained brain sections. Infarct volumes of rats undergoing pMCAO ranged from 0 to 48%. Data were divided into three groups based upon percent infarction: mild (0-20%), moderate (21-35%), and severe (>35%). A within-subject analysis revealed a significant decrease in mean startle amplitude of only severely infarcted rats relative to their pre-surgery startle responses. Furthermore, the lesioned brain areas observed in these animals provide an anatomical basis for these results. Our findings demonstrate that ASR is affected in a model of stroke. Further work is needed to characterize this behavioral test and to determine whether it may have application as a surrogate endpoint for clinical stroke studies.
authors.affiliation: Systems Pharmacology, CNS Disease Group, Sanofi Aventis Inc., 1041 Route 202-206, JR-2-303A Bridgewater, NJ 08807-0800, USA. Kenneth.Maynard@aventis.com
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Maynard
authors.forename: Stacey J
authors.initials: SJ
authors.lastname: Sukoff
authors.forename: Zhongqi
authors.initials: Z
authors.lastname: Ji
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Wettstein
authors.forename: Mark D
authors.initials: MD
authors.lastname: Black
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000704:Analysis of Variance; D000818:Animals; D020520:Brain Infarction / Q000473:pathology; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012022:Reflex, Acoustic / Q000502:physiology* / Q000528:radiation effects; D013216:Reflex, Startle / Q000502:physiology* / Q000528:radiation effects; D013778:Tetrazolium Salts
chemical_list: D013778:Tetrazolium Salts; C009591:triphenyltetrazolium