Paradoxical effects of acute ethanolism in experimental brain injury

Abstract

Acute ethanol intoxication is a frequent complicating factor in human head injury, yet its impact on neurological outcome remains poorly defined. This study was undertaken to assess the effect of varying levels of preinjury ethanol on early postinjury mortality, recovery of motor function, and degree of neural degeneration after cortical contusion injury in the rat. Adult rats were pretrained on a beam-walking task, then randomized to one of five groups: low-dose ethanol and injury (1 g/kg, 16 animals); moderate-dose ethanol and injury (2.5 g/kg, 11 animals); high-dose ethanol and injury (3 g/kg, 17 animals); no ethanol and injury (nine animals); or ethanol and sham injury (seven animals). Forty minutes after intraperitoneal injection of ethanol or saline, the rats received a pneumatic piston-induced contusion injury of the left primary motor cortex. Their beam-walking ability was assessed daily for the next 7 days. At 4 weeks postinjury, the brains were sectioned and the dimensions of the cortical lesions were determined. Preinjury ethanol administration was associated with an acute postinjury mortality rate of 29.5% (p < 0.05); the highest mortality rate (47.1%) occurred in the high-dose ethanol group, whereas no deaths occurred in the animals in the no ethanol or sham-injured groups (p < 0.01). However, injured animals receiving low- and moderate-dose ethanol had significantly less severe beam-walking impairment initially, and a more rapid return to normal beam-walking ability, compared to the no and high-dose ethanol groups (p < 0.05). Additionally, the mean lesion volumes were significantly smaller in the low- and moderate-dose ethanol treatment groups compared to the no and high-dose ethanol groups (23.2 +/- 8 mm3 and 29 +/- 6.7 mm3 vs. 52 +/- 8.8 mm3 and 53.7 +/- 10.9 mm3, respectively, p < 0.01). In this cortical contusion model, the presence of ethanol before injury appears to exert a potent neuroprotective effect when administered in low or moderate doses. This action is postulated to result from ethanol-induced inhibition of N-methyl-D-aspartate receptor-mediated excitotoxicity. The loss of neuroprotection and increased mortality rates observed with high-dose ethanol may be related to ethanol-induced hemodynamic and respiratory depression.

The Effects of Acute and Chronic Alcohol Ingestion on Outcome following Multiple Episodes of Mild Traumatic Brain Injury in Rats

“…Kelly et al 9 and Janis et al, 12 used controlled cortical impact to produce severe TBI. Many investigators have used FPI to create reproducible MWM deficits.…”

“…In addition, it was our intent to study repetitive episodes of minor head injury, which we were able to easily produce with the fluid percussion device. Kelly et al 9 showed neuroprotection by low levels of alcohol at the time of trauma by measurement of improvement in neurobehavioral beam walking tasks. These tasks are primarily of locomotor function, whereas the MWM assesses spatial learning capability.…”

“…Based on recent laboratory observations, 9,12 we believed that acute alcohol intoxication at the time of multiple episodes of head injury would be neuroprotective. If acute alcohol intoxication at the time of injury provided neuroprotection, the animals intoxicated at the time of trauma should have demonstrated better MWM performance than their nonintoxicated injured cohorts.…”

“…10,11 Kelly et al also suggested that the loss of neuroprotection at high alcohol doses could be due to the detrimental effects of alcohol on respiratory status and hemodynamics. 9 Janis et al 12 also found that low levels of alcohol intoxication at the time of TBI improved cognitive performance of rodents subjected to bilateral frontal cortical contusions produced by cortical impact. These investigators subjected animals injured while intoxicated to Morris Water Maze (MWM) testing, and determined that low levels of acute intoxication (serum alcohol levels of approximately 0.100 g/dL) provided neuroprotection as illustrated by enhanced spatial learning.…”

“…Kelly et al evaluated the effects of different levels of intoxication on cognitive behavior following controlled cortical impact injury in rats. 9 These investigators found that posttraumatic neurologic improvement as assessed by beam walking tasks was faster in animals receiving low and moderate doses of alcohol when compared with animals exposed to high doses or with no preinjury alcohol exposure. They concluded that low and moderate levels of alcohol were neuroprotective in the face of cortical impact injury, and speculated that this effect might be due at least in part to the effect of acute alcohol intoxication on N-methyl-D-aspartate (NMDA) receptor inhibition with subsequent inhibition of excitotoxicity.…”