RT Journal Article SR Electronic T1 White Matter Vulnerability to Ischemic Injury Increases with Age Because of Enhanced Excitotoxicity JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 1479 OP 1489 DO 10.1523/JNEUROSCI.5137-07.2008 VO 28 IS 6 A1 Selva Baltan A1 Elaine F. Besancon A1 Brianna Mbow A1 ZuCheng Ye A1 Margaret A. Hamner A1 Bruce R. Ransom YR 2008 UL http://www.jneurosci.org/content/28/6/1479.abstract AB Stroke incidence increases with age and this has been attributed to vascular factors. We show here that CNS white matter (WM) is intrinsically more vulnerable to ischemic injury in older animals and that the mechanisms of WM injury change as a function of age. The mouse optic nerve was used to study WM function. WM function in older animals (12 months) was not protected from ischemic injury by removal of extracellular Ca2+ or by blockade of reverse Na+/Ca2+ exchange, as is the case with young adults. Ischemic WM injury in older mice is predominately mediated by glutamate release and activation of AMPA/kainate-type glutamate receptors. Glutamate release, attributable to reverse glutamate transport, occurs earlier and is more robust in older mice that show greater expression of the glutamate transporter. The observation that WM vulnerability to ischemic injury is age dependent has possible implications for the pathogenesis of other age-related CNS conditions.