Selective Neuronal Loss in Ischemic Stroke and Cerebrovascular Disease

• Published in: Journal of cerebral blood flow and metabolism Vol. 34; no. 1; pp. 2 - 18
• Main Authors: Baron, Jean-Claude, Yamauchi, Hiroshi, Fujioka, Masayuki, Endres, Matthias
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.01.2014; Sage Publications Ltd; Nature Publishing Group
• Subjects: Animal models; Animals; Brain - diagnostic imaging; Brain - pathology; Brain Ischemia - diagnostic imaging; Brain Ischemia - pathology; Carotid Artery Diseases - diagnostic imaging; Carotid Artery Diseases - pathology; Carotid Artery, Internal - diagnostic imaging; Carotid Artery, Internal - pathology; Cell Death; Diffusion Magnetic Resonance Imaging; Humans; Infarction, Middle Cerebral Artery - diagnostic imaging; Infarction, Middle Cerebral Artery - pathology; Neurons - pathology; Positron-Emission Tomography; Review; Stroke - diagnostic imaging; Stroke - pathology; vascular cognitive impairment; carotid disease; 11C-flumazenil; cerebral ischemia; neuronal death; PET
• ISSN: 0271-678X; 1559-7016; 1559-7016
• DOI: 10.1038/jcbfm.2013.188

As a sequel of brain ischemia, selective neuronal loss (SNL)—as opposed to pannecrosis (i.e. infarction)—is attracting growing interest, particularly because it is now detectable in vivo. In acute stroke, SNL may affect the salvaged penumbra and hamper functional recovery following reperfusion. Rodent occlusion models can generate SNL predominantly in the striatum or cortex, showing that it can affect behavior for weeks despite normal magnetic resonance imaging. In humans, SNL in the salvaged penumbra has been documented in vivo mainly using positron emission tomography and 11C-flumazenil, a neuronal tracer validated against immunohistochemistry in rodent stroke models. Cortical SNL has also been documented using this approach in chronic carotid disease in association with misery perfusion and behavioral deficits, suggesting that it can result from chronic or unstable hemodynamic compromise. Given these consequences, SNL may constitute a novel therapeutic target. Selective neuronal loss may also develop at sites remote from infarcts, representing secondary ‘exofocal’ phenomena akin to degeneration, potentially related to poststroke behavioral or mood impairments again amenable to therapy. Further work should aim to better characterize the time course, behavioral consequences—including the impact on neurological recovery and contribution to vascular cognitive impairment—association with possible causal processes such as microglial activation, and preventability of SNL.