Differential response to ischemia in adjacent hippocampalsectors: neuronal death in CA1 versus neurogenesis in dentate gyrus.
Two hippocampal sectors show distinct responses to transient ischemia: the cornu Ammonis (CA)1 sector undergoes a delayed neuronal death followed by a lack of neuronal generation, while the dentate gyrus (DG) shows slight postischemic damage followed by an increased neurogenesis. Using the monkey experimental paradigm of transient whole brain global ischemia, the 'calpain-cathepsin hypothesis' was formulated in 1998. This hypothesis proposes that following ischemia calpain compromises the integrity of lysosomal membrane, causing a leakage of degrading hydrolytic enzymes--cathepsins--into the cytoplasm. Ischemia induces Ca(2+) mobilization, calpain activation, lysosomal membrane disruption, and cathepsin release, which all occur specifically in the CA1 sector and cause neuronal death. In the postischemic DG, a vascular niche has been implicated in adult neurogenesis, in that adventitial cells of the DG microvascular environment provoke postischemic up-reguation of neurogenesis with the aid of brain-derived neurotrophic factor and polysialylated form of the neural cell adhesion molecule. In parallel, Down's syndrome cell adhesion molecule has recently been shown to be expressed specifically in the neural progenitor cells of DG. In this review, we focus on the monkey experimental paradigm to reveal the remarkable contrasts between CA1 and DG in response to the ischemic insult.
Yamashima
Tetsumori
T
Department of Restorative Neurosurgery, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan. yamashim@med.kanazawa-u.ac.jp
Tonchev
Anton B
AB
Borlongan
Cesar V
CV
D000818:Animals; D017209:Apoptosis; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology; D004314:Down Syndrome / Q000378:metabolism* / Q000473:pathology; D000882:Haplorhini; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D009415:Nerve Net / Q000378:metabolism* / Q000473:pathology; D009416:Nerve Regeneration; D009474:Neurons / Q000378:metabolism* / Q000473:pathology