Reduction of brain edema and expression of aquaporins with acute ethanol treatment after traumatic brain injury.

OBJECT: Previous studies have demonstrated that traumatic brain injury (TBI) causes brain edema by allowing excessive water passage through aquaporin (AQP) proteins. To establish the potential neuroprotective properties of ethanol as a post-TBI therapy, in the present study the authors determined the effect of ethanol on brain edema, AQP expression, and functional outcomes in a post-TBI setting. METHODS: Adult male Sprague-Dawley rats weighing between 425 and 475 g received a closed head TBI in which Maramarou's impact-acceleration method was used. Animals were given a subsequent intraperitoneal injection of 0.5 g/kg or 1.5 g/kg ethanol at 60 minutes post-TBI and were killed 24 hours after TBI. Brains were subsequently examined for edema along with AQP mRNA and protein expression. Additional animals treated with either 0.5 g/kg or 1.5 g/kg ethanol at 60 minutes post-TBI were designated for cognitive and motor testing for 3 weeks. RESULTS: Ethanol administration post-TBI led to significantly (p < 0.05) lower levels of brain edema as measured by brain water content. This downregulation in brain edema was associated with significantly (p < 0.05) reduced levels of AQP mRNA and protein expression as compared with TBI without treatment. These findings concur with cognitive studies in which ethanol-treated animals exhibited significantly (p < 0.05) faster radial maze completion times. Motor behavioral testing additionally demonstrated significant (p < 0.05) beneficial effects of ethanol, with treated animals displaying improved motor coordination when compared with untreated animals. CONCLUSIONS: The present findings suggest that acute ethanol administration after a TBI decreases AQP expression, which may lead to reduced cerebral edema. Ethanol-treated animals additionally showed improved cognitive and motor outcomes compared with untreated animals.

G-protein beta subunit of Cochliobolus heterostrophus involved in virulence, asexual and sexual reproductive ability, and morphogenesis.

Previous work established that mutations in mitogen-activated protein (MAP) kinase (CHK1) and heterotrimeric G-protein alpha (Galpha) subunit (CGA1) genes affect the development of several stages of the life cycle of the maize pathogen Cochliobolus heterostrophus. The effects of mutating a third signal transduction pathway gene, CGB1, encoding the Gbeta subunit, are reported here. CGB1 is the sole Gbeta subunit-encoding gene in the genome of this organism. cgb1 mutants are nearly wild type in vegetative growth rate; however, Cgb1 is required for appressorium formation, female fertility, conidiation, regulation of hyphal pigmentation, and wild-type virulence on maize. Young hyphae of cgb1 mutants grow in a straight path, in contrast to those of the wild type, which grow in a wavy pattern. Some of the phenotypes conferred by mutations in CGA1 are found in cgb1 mutants, suggesting that Cgb1 functions in a heterotrimeric G protein; however, there are also differences. In contrast to the deletion of CGA1, the loss of CGB1 is not lethal for ascospores, evidence that there is a Gbeta subunit-independent signaling role for Cga1 in mating. Furthermore, not all of the phenotypes conferred by mutations in the MAP kinase CHK1 gene are found in cgb1 mutants, implying that the Gbeta heterodimer is not the only conduit for signals to the MAP kinase CHK1 module. The additional phenotypes of cgb1 mutants, including severe loss of virulence on maize and of the ability to produce conidia, are consistent with CGB1 being unique in the genome. Fluorescent DNA staining showed that there is often nuclear degradation in mature hyphae of cgb1 mutants, while comparable wild-type cells have intact nuclei. These data may be genetic evidence for a novel cell death-related function of the Gbeta subunit in filamentous fungi.