Competing processes of cell death and recovery of function following ischemic preconditioning.
The goal of the present study was to determine the neuroprotective efficacy of ischemic preconditioning using behavioral, electrophysiological and histological endpoints at various time points up to 90 days postischemia. Gerbils were exposed to a brief, non-injurious episode of forebrain ischemia (1.5 min) on each of 2 consecutive days. Three days following this preconditioning procedure, the animals received a 5 min occlusion. Other animals underwent sham surgery or a 5 min occlusion without preconditioning. Ischemic preconditioning appeared to provide striking histological protection at both rostral (approximately 80% and approximately 67% of sham) and posterior levels of hippocampus (approximately 94% and approximately 78% of sham) at 3 and 10 days survival, respectively. However, in spite of the near normal number of CA1 neurons, animals displayed marked impairments in an open field test of habituation as well as reduced dendritic field potentials in the CA1 area. Additionally, in ischemic animals the basal and apical dendritic regions of CA1 were nearly devoid of the cytoskeletal protein microtubule associated protein 2 (MAP2). Staining levels of MAP2 in preconditioned and sham animals were similar. With increasing survival time, open field behavior as well as CA1 field potential amplitude recovered. Nonetheless, CA1 cell death in ischemic preconditioned animals continued over the 90-day survival period (P<0.05, vs. sham levels). Ischemic preconditioning provides a significant degree of neuroprotection characterized by a complex interplay of protracted cell death and neuroplasticity (recovery of function). These competing processes are best elucidated using a combination of functional and histological endpoints as well as multiple and extended survival times (i.e., greater than 7-10 days).
Dooley
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P
Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NF, Canada.
Corbett
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D
D000818:Animals; D001833:Body Temperature Regulation / Q000502:physiology; D002452:Cell Count; D016923:Cell Death; D019706:Excitatory Postsynaptic Potentials; D005106:Exploratory Behavior / Q000502:physiology*; D005260:Female; D005849:Gerbillinae; D006624:Hippocampus / Q000098:blood supply*; D007150:Immunohistochemistry; D019194:Ischemic Preconditioning; D008869:Microtubule-Associated Proteins / Q000378:metabolism
D008869:Microtubule-Associated Proteins