Effects of binge ethanol administration on the behavioral outcome of rats after lateral fluid percussion brain injury.

This study examined the effects of 4 weeks of binge ethanol administration (BEAn) on the behavioral outcome in rats after lateral fluid percussion (FP) brain injury. Rats were intragastrically given 7.5 mL/kg of either 40% ethanol in 5% glucose solution (3 g ethanol/kg; binge ethanol group), or 5% glucose solution (vehicle group), twice on Thursday and Friday of 3 consecutive weeks. Then rats from both groups were subjected to either lateral FP brain injury of moderate severity (1.8 atm) or to sham operation. Postinjury behavioral measurements revealed that brain injury caused significant spatial learning disability in both groups. There were no significant differences in mean search latencies in the sham animals between the vehicle and binge ethanol groups. On the other hand, the mean search latency of the binge ethanol group was significantly higher than that of the vehicle group in trial blocks 2 and 4. There were no significant differences in the target visits (expressed as mean zone difference [MZD]) during the probe trial between the injured animals of binge ethanol and vehicle groups. However, there was only a minor trend towards worsened MZD score in the binge-injured animals. Histologic analysis of injured animals from both injured ethanol and vehicle groups revealed similar extents of ipsilateral cortical and observable hippocampal damage. These results suggest that 4 weeks of binge ethanol treatment followed by ethanol intoxication at the time of injury worsens some aspects of the spatial learning ability of rats. This worsening is probably caused by subtle, undetectable morphologic damage by binge ethanol administration.

Lupines, manganese, and devil-sickness: an Anglo-Saxon medical response to epilepsy.

The most frequently prescribed herb for "devil-sickness" in the vernacular medical books from Anglo-Saxon England, the lupine, is exceptionally high in manganese. Since manganese depletion has been linked with recurring seizures in both clinical and experimental studies, it is possible that lupine administration responded to the particular pathophysiology of epilepsy. Lupine is not prescribed for seizures in classical Mediterranean medical sources, implying that the Northern European peoples (if not the Anglo-Saxons themselves) discovered whatever anticonvulsive properties the herb may exhibit.

Regional expression of Par-4 mRNA and protein after fluid percussion brain injury in the rat.

Regional levels of prostate apoptosis response-4 (Par-4) protein and mRNA were measured after lateral fluid percussion (FP) brain injury in rats. Immunochemical studies indicated that Par-4 immunoreactivity (ir) is present in cortical neurons and hippocampal CA1-CA3 pyramidal neurons in uninjured rats. Increases of Par-4-ir were observed in the CA3 neurons of the ipsilateral hippocampus (IH), but not in injured left cortex (IC) at 48 h after FP brain injury. Levels of the Par-4 mRNA measured by RT-PCR assay and protein measured by Western blot procedure were significantly increased in the injured IC and IH, but not in the contralateral right cortex and hippocampus after brain injury. Levels of both Par-4 protein and mRNA were significantly increased in the IC and IH as early as 2 h and stayed elevated at 24 and 48 h after injury. These data show that the induction of proapoptotic Par-4 mRNA and protein occurs only in the IC and IH that have been observed to undergo apoptosis and neuronal cell loss after lateral FP brain injury. Because increased expression of Par-4 has been observed to contribute to apoptosis and cell death in cultured neurons, the present temporal pattern of Par-4 expression is consistent with a role for Par-4 in apoptosis and neuronal cell death after traumatic brain injury.

Regional expression of Bcl-2 mRNA and mitochondrial cytochrome c release after experimental brain injury in the rat.

Regional levels of anti-apoptotic Bcl-2 mRNA and the cytosolic cytochrome c protein were measured after lateral fluid percussion (FP) brain injury in rats. Levels of Bcl-2 mRNA were significantly decreased in the injured left cortex (IC) and ipsilateral hippocampus (IH), but not in the contralateral right cortex (CC) and hippocampus (CH) after brain injury. Levels of Bcl-2 mRNA were significantly decreased as early as 2 h and stayed decreased as long as 48 h in the IC and IH after injury. Levels of the cytosolic cytochrome c protein were significantly increased in the IC and IH, but not in the CC and CH after brain injury. Levels of cytosolic cytochrome c were significantly increased in the IC at 30 min, 48 and 72 h, and in the IH at 2 h and as long as 72 h after injury. The increase of cytosolic cytochrome c suggests that the mitochondrial release of cytochrome is increased in the IC and IH after lateral FP brain injury. These data show that the reduction of anti-apoptotic Bcl-2 and increases of mitochondrial release of cytochrome c protein occur only in the IC and IH, regions which have been observed to undergo apoptosis and neuronal cell loss after lateral FP brain injury. Therefore, it is likely that the reduction of Bcl-2 and the increased cytochrome c protein in the cytosol contribute to the observed apoptosis and neuronal cell death in the IC and IH after lateral FP brain injury in rats.

Three months of chronic ethanol administration and the behavioral outcome of rats after lateral fluid percussion brain injury.

This study examined the effects of 3 months of chronic ethanol administration (CEAn) on the behavioral outcome in rats after lateral fluid percussion (FP) brain injury. Rats were given either an ethanol liquid diet (ethanol diet groups) or a pair-fed isocaloric sucrose control diet (control diet groups) for 3 months. Then, rats from both diet groups were subjected to either lateral FP brain injury of moderate severity (1.8 atm) or to sham operation. Postinjury behavioral measurements revealed that brain injury caused significant spatial learning disability in both diet groups. There were no significant differences in spatial learning ability in the sham or brain-injured animals between the control and ethanol diets. However, a trend towards cognitive impairment in the sham animals and a trend towards reduced deficits in the brain-injured animals were observed in the ethanol diet group. Histologic analysis of injured animals from both diet groups revealed similar extents of ipsilateral cortical and hippocampal CA3 damage. These results, in general, suggest that 3 months of CEAn does not significantly alter the behavioral and morphologic outcome of experimental brain injury.