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Summary: Immediately following concussive brain in jury, cells exhibit an increase of energy demand repre sented by the activation of glucose utilization. We have proposed that this trauma-induced hypermetabolism re flects the effort of cells to restore normal ionic balance disrupted by massive ionic fluxes through transmitter gated ion channels. In the present study, changes in local CMR g lc following fluid-percussion concussive injury were determined using [14C]2-deoxy-n-glucose autoradi ography, and the effects of in situ administration (via mi crodialysis) of excitatory amino acid (EAA) antagonists [kynurenic acid (KYN), 2-amino-5-phosphonovaleric acid (APV; 100 fJ,M, I mM, and 10 mM), and 6-cyano-7-nitroquinoxaline-2,3-dine (CNQX; 300 fJ,M, I mM, and 10 mM] on glucose utilization were investigated. Animals that did not receive dialysis showed a remarkable inIn recent work using microdialysis, the changes in extracellular potassium ([K + ] e ) and the release of excitatory amino acids (EAAs) have been docu mented following experimental concussive (Katayama et aI. , 1988(Katayama et aI. , , 1990) and contusion (Faden et aI., 1989; Nilsson et aI. , 1990) brain injury. InRe

The O6‐methylguanine‐DNA methyltransferase (MGMT) plays a major role in repairing DNA damage from alkylating agents. In several human neoplasms including low‐grade diffuse astrocytomas, promoter hypermethylation of MGMT has been shown to correlate with an increased frequency of p53 mutation. In the present study, we analyzed MGMT promoter methylation by the methylation‐specific PCR in 49 newly diagnosed WHO grade II astrocytomas and evaluated its clinical usefulness. MGMT promoter methylation was found in 21 (43%) of the 49 tumors. A tight correlation existed between MGMT methylation and p53 protein accumulation (P=0.0424). The presence of MGMT methylation was significantly associated with a shorter progression free survival (PFS) on both univariate analysis (P=0.0014) and multivariate analysis (P=0.0081). It was a more powerful determinant of the PFS than age, sex, performance status, proliferative activity, or p53 expression, and was independent of the extent of surgery. In terms of the overall survival, MGMT methylation demonstrated a prognostic utility in the univariate analysis but not in the multivariate analysis. The present findings indicate that aberrant methylation of the MGMT promoter independently augurs for an unfavorable clinical course in patients with low‐grade diffuse astrocytomas. Since the presence of MGMT methylation is expected to predict an increased sensitivity to alkylating chemotherapeutic agents, earlier chemotherapy could serve to improve an unfavorable natural history in tumors with MGMT methylation.