QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, February 6, 2008, 28(6):1479-1489; doi:10.1523/JNEUROSCI.5137-07.2008

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Baltan, S. Articles by Ransom, B. R. PubMed PubMed Citation Articles by Baltan, S. Articles by Ransom, B. R.

 Previous Article  |  Next Article 

Neurobiology of Disease
White Matter Vulnerability to Ischemic Injury Increases with Age Because of Enhanced Excitotoxicity

Selva Baltan,¹ Elaine F. Besancon,² Brianna Mbow,¹ ZuCheng Ye,¹ Margaret A. Hamner,¹ and Bruce R. Ransom¹

¹Department of Neurology, Harborview Medical Center, Seattle, Washington 98104, and ²School of Medicine, Harvard University, Boston, Massachusetts 02115

Correspondence should be addressed to Dr. Selva Baltan, Department of Neurology, Box 359665, Harborview Medical Center, Room R&T 413, 325 Ninth Avenue, Seattle, WA 98104. Email: selva{at}u.washington.edu

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.

Key words: glutamate; glutamate transporter; axon; NMDA receptors; stroke; AMPA/kainate receptors

---

Received Sept. 19, 2007; revised Dec. 20, 2007; accepted Dec. 27, 2007.

Correspondence should be addressed to Dr. Selva Baltan, Department of Neurology, Box 359665, Harborview Medical Center, Room R&T 413, 325 Ninth Avenue, Seattle, WA 98104. Email: selva{at}u.washington.edu

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help