Cohan Charles H, Neumann Jake T, Dave Kunjan R, Alekseyenko Aleksey, Binkert Marc, Stransky Kenneth, Lin Hung Wen, Barnes Carol A, Wright Clinton B, Perez-Pinzon Miguel A
Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, United States of America; Evelyn F. McKnight Brain Institute, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, United States of America; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, United States of America; Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, United States of America.
Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, United States of America; Evelyn F. McKnight Brain Institute, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, United States of America; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, United States of America.
PLoS One. 2015 May 1;10(5):e0124918. doi: 10.1371/journal.pone.0124918. eCollection 2015.
Cardiopulmonary arrest is a leading cause of death and disability in the United States that usually occurs in the aged population. Cardiac arrest (CA) induces global ischemia, disrupting global cerebral circulation that results in ischemic brain injury and leads to cognitive impairments in survivors. Ischemia-induced neuronal damage in the hippocampus following CA can result in the impairment of cognitive function including spatial memory. In the present study, we used a model of asphyxial CA (ACA) in nine month old male Fischer 344 rats to investigate cognitive and synaptic deficits following mild global cerebral ischemia. These experiments were performed with the goals of 1) establishing a model of CA in nine month old middle-aged rats; and 2) to test the hypothesis that learning and memory deficits develop following mild global cerebral ischemia in middle-aged rats. To test this hypothesis, spatial memory assays (Barnes circular platform maze and contextual fear conditioning) and field recordings (long-term potentiation and paired-pulse facilitation) were performed. We show that following ACA in nine month old middle-aged rats, there is significant impairment in spatial memory formation, paired-pulse facilitation n dysfunction, and a reduction in the number of non-compromised hippocampal Cornu Ammonis 1 and subiculum neurons. In conclusion, nine month old animals undergoing cardiac arrest have impaired survival, deficits in spatial memory formation, and synaptic dysfunction.
心脏骤停是美国导致死亡和残疾的主要原因，通常发生在老年人群中。心脏骤停（CA）会引发全身性缺血，扰乱全脑循环，导致缺血性脑损伤，并使幸存者出现认知障碍。心脏骤停后海马体中缺血诱导的神经元损伤可导致包括空间记忆在内的认知功能受损。在本研究中，我们使用9个月大的雄性Fischer 344大鼠的窒息性心脏骤停（ACA）模型，来研究轻度全脑缺血后的认知和突触缺陷。进行这些实验的目的是：1）在9个月大的中年大鼠中建立心脏骤停模型；2）检验中年大鼠轻度全脑缺血后会出现学习和记忆缺陷这一假设。为了验证这一假设，我们进行了空间记忆测试（巴恩斯圆形平台迷宫和情境恐惧条件反射）以及场电位记录（长时程增强和双脉冲易化）。我们发现，9个月大的中年大鼠在经历ACA后，空间记忆形成、双脉冲易化功能均有显著受损，未受损的海马齿状回1区和下托神经元数量减少。总之，经历心脏骤停的9个月大动物存活能力受损，空间记忆形成存在缺陷，且有突触功能障碍。
