White Matter Injury in Global Cerebral Ischemia
In chronic cerebral hypoperfusion due to aging, global cerebral ischemia after cardiac arrest, acute and chronic hypoxia in asymptomatic stroke, and diffuse axonal injury after traumatic brain injury, white matter lesions occur not only as a result of secondary degeneration caused by neuronal injuries in the gray matter, but also as a direct consequence of the primary ischemic insults. Not enough attention has been directed to the molecular and cellular mechanisms of white matter injuries in humans. Failures in past stroke therapyclinical trials are partly attributed to misrepresentation of the relevance of white matter to human brain pathology in the preclinical data. Most rodent models either ignore white matter's contribution to the injury process and recovery, or inadequately account for this contribution due to a significantly lower proportion of white matter in the rodent brain compared to the human brain. Future development of effective therapies should place an equal emphasis on gray and white matter injuries.
KeywordsWhite Matter Traumatic Brain Injury Cardiac Arrest Axonal Injury Global Cerebral Ischemia
The authors would like to acknowledge the support from the National Institutes of Health (R01NS036124) and from the Department of Anesthesiology at the University of Pittsburgh.
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