Ethanol reduces metabolic uncoupling following experimental head injury.
Previous investigations have shown that ethanol is neuroprotective following experimental traumatic brain injury (TBI). This study sought to determine if the neuroprotective effects of ethanol in a controlled cortical impact (CCI) injury model are related to its effects on cerebral glucose metabolism and blood flow. Adult rats were given ethanol (1.0 g/kg) or saline by intraperitoneal injection followed 40 min later by injury. Regional cerebral blood flow (CBF) and cerebral metabolic rates of glucose (CMRglc) were determined immediately, and at 3, 6, 12, 24, and 72 h postinjury using quantitative autoradiography. Immediately after injury, CMRglc in the contusion core and penumbra was reduced in the ethanol group compared to the saline group: (core CMRglc: 52.2 +/- 16.0 versus 94.2 +/- 14.1 micromol/100 g/min, respectively,p < 0.001; penumbral CMRglc: 58.2 +/- 12.8 versus 82.8 +/-19.7 micromol/100 g/min, respectively; p < 0.05) However, at 24 and 72 h postinjury, penumbral CMRglc in the ethanol group was increased compared to the saline group (p < 0.05 and p < 0.001, respectively). Regarding CBF, contusion core values in the ethanol group were elevated compared to the saline group immediately postinjury, (70.4 +/- 17.1 versus 31.5 +/- 27.8 mL/100 g/min, respectively (p < .05), and at 6, 12, and 24 h postinjury (p < 0.05). Penumbral CBF was also higher at 6 and 72 h in the ethanol group compared to the saline group (p < 0.05). These results indicate that low-dose ethanol is associated with a marked attenuation of immediate postinjury hyperglycolysis and with more normal glucose metabolism in the injury penumbra over the ensuing 3 days. Simultaneously, the reduction in CBF typically seen within the contusion core and penumbra after CCI is less severe when ethanol is present. The net effect of these changes is a decreased degree of uncoupling between glucose metabolism and CBF that otherwise occurs in the absence of ethanol. These changes may likely explain the neuroprotective effect of ethanol.
Kelly
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DF
The Division of Neurosurgery, UCLA Brain Injury Research Center, UCLA School of Medicine, Los Angeles, California 90095-7039, USA. dfkelly@ucla.edu
Kozlowski
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DA
Haddad
E
E
Echiverri
A
A
Hovda
D A
DA
Lee
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SM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics; D000983:Antipyrine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D001345:Autoradiography; D001930:Brain Injuries / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010296:Parietal Lobe / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002250:Carbon Radioisotopes; D018696:Neuroprotective Agents; D000431:Ethanol; D005947:Glucose; D000983:Antipyrine; C008135:iodoantipyrine