Maynard Kenneth I, Sukoff Stacey J, Ji Zhongqi, Wettstein Joseph G, Black Mark D
Systems Pharmacology, CNS Disease Group, Sanofi Aventis Inc., 1041 Route 202-206, JR-2-303A Bridgewater, NJ 08807-0800, USA.
Brain Res. 2005 Jan 25;1032(1-2):44-9. doi: 10.1016/j.brainres.2004.10.065.
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.
惊吓反射是一种用于研究感觉模态的无条件、可量化行为。我们研究了听觉惊吓反射(ASR)对局灶性脑缺血诱导的损伤是否敏感。在手术前3 - 6天对Sprague-Dawley大鼠进行惊吓反射反应的预筛选,各实验组间平均惊吓幅度无差异。动物接受永久性大脑中动脉闭塞(pMCAo)或假手术。24小时后,在处死大鼠前评估其ASR。随后通过对2,3,5 - 氯化三苯基四氮唑染色的脑切片进行定量图像分析来确定梗死体积。接受pMCAO的大鼠梗死体积范围为0至48%。根据梗死百分比将数据分为三组:轻度(0 - 20%)、中度(21 - 35%)和重度(>35%)。受试者内分析显示,只有重度梗死大鼠相对于其术前惊吓反应,平均惊吓幅度显著降低。此外,在这些动物中观察到的损伤脑区为这些结果提供了解剖学依据。我们的研究结果表明,在中风模型中ASR受到影响。需要进一步开展工作来描述这种行为测试,并确定它是否可作为临床中风研究的替代终点。