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J Cereb Blood Flow Metab. 2014 Jan;34(1):2-18. doi: 10.1038/jcbfm.2013.188. Epub 2013 Nov 6.

Selective neuronal loss in ischemic stroke and cerebrovascular disease.

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INSERM U894, Centre Hospitalier Sainte Anne, Sorbonne Paris Cité, Paris, France.
Division of PET Imaging, Shiga Medical Center Research Institute, Moriyama, Japan.
Neuroscience Unit, Critical Care Medical Center, Nara Medical University, Nara, Japan.
Klinik und Hochschulambulanz für Neurologie, Center for Stroke Research Berlin, and ExcellenceCluster NeuroCure, Charité- Universitätsmedizin Berlin, Berlin, Germany.


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 (11)C-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.

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