Metabolic alterations in cerebrospinal fluid from double hemorrhage model of dogs.
OBJECTIVE
Even though cerebral vasospasm after subarachnoid hemorrhage (SAH) causes cerebral ischemia or infarction, the metabolic alterations in cerebrospinal fluids (CSF) after SAH have not been studied. This study was undertaken to measure the levels of glucose, lactate, pyruvate and glutamate in CSF from double hemorrhage dog models.


METHODS
Thirty-two mongrel dogs of either sex, weighing 15-30 kg, underwent double hemorrhage by percutaneous needle puncture of the cisterna magna and injection of autologous blood on day 0 and day 2. The dogs were then sacrificed on day 3, 5 and 7, after collecting CSF. In another study, the dogs were treated with mitogen-activated protein kinase (MAPK) inhibitors PD98059 and U0126, and caspase-2 and caspase-3 inhibitors from day 3 to day 6 after initial blood injection. CSF was collected on day 7 before dogs were sacrificed. The concentration of glucose, lactate, pyruvate and glutamate in CSF was measured by photometrical method.


RESULTS
Compared with CSF collected on day 0, glucose was decreased on days 5-7, lactate was increased on days 2-7, pyruvate was increased on days 2-7, and glutamate was increased on days 3-7 (P < 0.05). In the groups treated with MAPK or caspase inhibitors, most of the metabolic alterations remained unchanged as compared with CSF from untreated dogs. Clinically, caspase inhibitors-2 and -3, and MAPK inhibitor U0126 all failed to prevent vasospasm. MAPK inhibitor PD98059 partially prevented vasospasm.


CONCLUSIONS
Our data demonstrated a metabolic alteration of glucose, glutamate, lactate and pyruvate in CSF during cerebral vasospasm. This metabolic change is consistent with the time course of cerebral vasospasm. This study suggests that brain energy metabolites and excitative amino acids are altered during cerebral vasospasm.
Yin
W
W
Department of Neurosurgery, University of Mississippi Medical Center, Jackson, MS, USA.
Tibbs
R
R
Aoki
K
K
Badr
A
A
Zhang
J
J
D000704:Analysis of Variance; D000818:Animals; D061945:Caspase Inhibitors; D002543:Cerebral Hemorrhage / Q000134:cerebrospinal fluid* / Q000150:complications; D004195:Disease Models, Animal; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D005947:Glucose / Q000134:cerebrospinal fluid*; D018698:Glutamic Acid / Q000134:cerebrospinal fluid*; D007773:Lactates / Q000134:cerebrospinal fluid*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019289:Pyruvic Acid / Q000134:cerebrospinal fluid*; D013997:Time Factors; D020301:Vasospasm, Intracranial / Q000134:cerebrospinal fluid* / Q000209:etiology
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007773:Lactates; D018698:Glutamic Acid; D019289:Pyruvic Acid; D020928:Mitogen-Activated Protein Kinases; D005947:Glucose; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one