CSF glutamate during hypoxia-ischemia in the immature rat

Cerebrospinal fluid (CSF) glutamate was measured prior to and during the co urse of cerebral hypoxia-ischemia in the immature rat to estimate its conce ntration in the extracellular fluid (ECF). A preliminary experiment was con ducted using [C-14]glutamate injections into immature rat brain, which show ed that equilibration between ECF and CSF occurred within 10 min. Seven-day postnatal rats underwent unilateral common carotid artery Ligation followe d by hypoxia with 8% oxygen for up to 2 h. Brain damage, in the form of sel ective neuronal necrosis or apoptosis, commences after 60 min, while infarc tion commences after 90 min of hypoxia-ischemia. During the course of hypox ia-ischemia, CSF was obtained from the cisterna magna and analyzed for glut amate. No statistically significant increases in CSF glutamate occurred unt il 105 min, at which time the concentration was 240% of control (20 mu mol/ l). By 120 min, CSF glutamate had increased over twofold above the control value. In rat pups exposed to 1 h of hypoxia-ischemia, no increases in CSF glutamate occurred for up to 6 h of recovery. In animals exposed to 2 h of hypoxia-ischemia, CSF glutamate decreased to the control value by 1 h of re covery, with a secondary rise at 6 h, Accordingly, the increase in CSF, and presumably ECF, glutamate is a late event, which better corresponds tempor ally to cerebral infarction than to selective neuronal death. The results s uggest that glutamate excitotoxicity, although involved in the occurrence o f infarction, neither causes or contributes to selected neuronal death. The secondary elevation in CSF glutamate at 6 h of recovery from 2 h of hypoxi a-ischemia occurs coincident with the onset of tissue necrosis, seen histol ogically. (C) 1999 Elsevier Science B.V. All rights reserved.