Early onset of demyelination after N-methyl-D-aspartate lesions of the lateral hypothalamus

The function of neurons residing in a particular brain area is often assessed by injecting glutamatergic excitotoxins into that area and determining the consequences for the behavior of interest. However, injections of excitotoxins into the central nervous system not only kill local neurons but also demyelinate fibers of passage. Previous studies suggest that the myelin damage is triggered by a delayed inflammatory response to cell death mediated by monocytes of peripheral origin. If so, demyelination should commence only after recruitment of monocytes, their passage through the blood-brain barrier, and their metamorphosis into macrophages. This process is estimated to require at least 48 h. Using a hematoxylin (Weil) stain and immunohistochemistry for myelin basic protein, we looked for signs of demyelination at various times after injections of N-methyl-D-aspartate into the lateral hypothalamus. Demyelination was seen within 24 h after the lesion, sooner than predicted by the monocytic infiltration hypothesis. This finding has implications for interpreting effects of excitotoxic lesions and for developing means of improving their specificity. (C) 1999 Elsevier Science B.V. All rights reserved.