CSF glutamate during hypoxia-ischemia in the immature rat.
Cerebrospinal fluid (CSF) glutamate was measured prior to and during the course of cerebral hypoxia-ischemia in the immature rat to estimate its concentration in the extracellular fluid (ECF). A preliminary experiment was conducted using [14C]glutamate injections into immature rat brain, which showed that equilibration between ECF and CSF occurred within 10 min. Seven-day postnatal rats underwent unilateral common carotid artery ligation followed by hypoxia with 8% oxygen for up to 2 h. Brain damage, in the form of selective neuronal necrosis or apoptosis, commences after 60 min, while infarction commences after 90 min of hypoxia-ischemia. During the course of hypoxia-ischemia, CSF was obtained from the cisterna magna and analyzed for glutamate. No statistically significant increases in CSF glutamate occurred until 105 min, at which time the concentration was 240% of control (20 micromol/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 recovery, with a secondary rise at 6 h. Accordingly, the increase in CSF, and presumably ECF, glutamate is a late event, which better corresponds temporally to cerebral infarction than to selective neuronal death. The results suggest that glutamate excitotoxicity, although involved in the occurrence of infarction, neither causes or contributes to selected neuronal death. The secondary elevation in CSF glutamate at 6 h of recovery from 2 h of hypoxia-ischemia occurs coincident with the onset of tissue necrosis, seen histologically.
Vannucci
R C
RC
Department of Pediatrics (Pediatric Neurology), The Pennsylvania State University College of Medicine, Hershey, PA, USA.
Brucklacher
R M
RM
Vannucci
S J
SJ
D000818:Animals; D000831:Animals, Newborn / Q000134:cerebrospinal fluid* / Q000378:metabolism; D002545:Brain Ischemia / Q000134:cerebrospinal fluid* / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D018698:Glutamic Acid / Q000134:cerebrospinal fluid* / Q000378:metabolism; D000860:Hypoxia / Q000134:cerebrospinal fluid* / Q000378:metabolism; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D018698:Glutamic Acid