Metabolic alterations in cerebrospinal fluid from double hemorrhage model of dogs

Even though cerebral vasospasm after subarachnoid hemorrhage (SAH) causes c erebral 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. Thirty-two mongrel dogs of either sex, weighi ng 18-24 kg, underwent double hemorrhage by percutaneous needle puncture of the cisterna magna and injection of autologous blood on day 0 and day 2. T he dogs were then sacrificed on day 3, 5 and 7 after collecting CSF. In ano ther study, the dogs were treated with mitogen-activated protein kinase (MA PK) inhibitors PD98059 and U0126, and caspase-2 and caspase-3 inhibitors fr om day 3 to day 6 after initial blood injection. CSF was collected on day 7 before dogs were sacrificed. The concentration of glucose, lactate, pyruva te and glutamate in CSF was measured by photometrical method. Compared with CSF collected on day 0, glucose was decreased on days 5-7, lactate was inc reased on days 2-7, pyruvate was increased on days 2-7, and glutamate was i ncreased on days 3-7 (p < 0.05). In the groups treated with MAPK or caspase inhibitors, most of the metabolic alterations remained unchanged as compar ed with CSF from untreated dogs. Clinically, caspase inhibitors-2 and -3, a nd MAPK inhibitor U0126 all failed to prevent vasospasm. MAPK inhibitor PD9 8059 partially prevented vasospasm. Our data demonstrated a metabolic alter ation of glucose, glutamate, lactate and pyruvate in CSF during cerebral va sospasm. This metabolic change is consistent with the time course of cerebr al vasospasm. This study suggests that brain energy metabolites and excitat ive amino acids are altered during cerebral vasospasm.