Effect of Cardiac Arrest on Cognitive Impairment and Hippocampal Plasticity in Middle-Aged Rats

Abstract

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.

Physical Exercise Improves Cognitive Outcomes in 2 Models of Transient Cerebral Ischemia

“…Additionally, ischemia-induced enhancement of plasticity may be limited further from the infarct 13 . Here, we tested cognition with hippocampal-dependent contextual fear conditioning 7 . Our previous studies find no gross neuronal loss in the hippocampus after focal ischemia 5 and extensive hippocampal neuronal loss after global ischemia 14 .…”

“…Focal cerebral ischemia was achieved with intraluminal suture blockage of the middle cerebral artery for 90 minutes 5, 6 . Global cerebral ischemia was induced with 8-minute asphyxia cardiac arrest 5, 7 . Physiological parameters were maintained within normal ranges during surgeries (Online Supplement).…”

“…Eighteen days after surgery (8–10 days after exercise), hippocampal-dependent contextual fear conditioning was performed 7 . Rats were placed into the operant conditioning chamber (Coulbourn Instruments, Whitehall, PA) for 370 seconds with a 2 second 1.5 mA shock administered at second 340.…”

Hypoxia/ischemia activate processing of Amyloid Precursor Protein: impact of vascular dysfunction in the pathogenesis of Alzheimer's disease

“…Moreover, cerebral ischemia can impair cognitive functions, e.g. spatial learning and memory, and aggravate Ab-induced cognitive deficiencies (Kiryk et al 2011;Li et al 2011;Cohan et al 2015).…”

Dysregulation of Autophagy, Mitophagy, and Apoptosis Genes in the CA3 Region of the Hippocampus in the Ischemic Model of Alzheimer’s Disease in the Rat

“…Transient ischemic brain injury and Alzheimer's disease (AD) are two known disorders characterized by progressive neurodegeneration, which initially triggers neuronal death in the hippocampus in the CA1 region and then in the CA3 area [1][2][3][4][5], ulti-mately leading to the development of dementia [6][7][8]. It has been observed that post-ischemic dementia is associated with both the progressive loss of pyramidal neurons of the CA1 and CA3 hippocampal areas, as well as its gradual atrophy [3,4,9,10], in the same way as in AD [5,11].…”