| Background: Status epilepticus (SE) is a medical emergency, and it may induce central nervous system (CNS) injury and associated with significant mortality and complications.Brain edema is one of pathological states following SE.BE accounts for much of the morbidity and mortality associated with various acute neurologic disorders including SE.Treatment options about brain edema are limited to osmotic agents such as mannitol, surgical ecompression, and other maneuvers, none of which correct the molecular-level mechanisms responsible for brain swelling. A family of molecular water channels called aquaporins(AQPs),which has been recently identified in mammals may provide the major route for water movement across plasma membranes in many cell types. AQP4 is a water-selective transporter and expressedwidely throughout the brain, particularly in astrocyte foot processes near capillaries and in ependymal cells, This distribution suggests the involvement of AQP4 in the movement of water between blood and brain and between brain and cerebrospinal fluid (CSF).AQP4 expression is markedly increased in experimental models of brain injury and ischemia and transgenic mice lacking AQP4 are partially protected from brain swelling in response to acute hyponatremia and ischemic stroke. These results implicate a key role for AQP4 in modulating brain water transport and participating brain edema formation,and suggest that AQP4 inhibition might offer a new therapeutic option for brain edema. Objectives: The study was to investigate the relationship between aquaporin-4 (AQP4) and brain edema following status epilepticus(SE) via observing the changes of AQP4 expression in brain edema formation following SE in the developing rats, and to clarify the formation mechanisms of brain edema following SE. We also observed the effects of Monosialote — trahexosylganglioside (GM1) on the expression of AQP4 and brain edema following SE, contributing to learn more about the protective function of GM1 on brain edema due to SE. Methods: One hundreds and fifty male developing Spraque-Dawley (SD) rats were randomly divided into three groups: control group, statusepilepticus group (SE group) which was induced by Pilocarpine (PILO), and GM1 group (SE+GM1), in which the rats were given intraperitoneal injection of GM1 30mg/kg after SE,once again every 24h for six times. Each group was subjected to 4 subgroups:6 h, 24 h, 72h and 7d after SE (n=5) . Each cerebral cortical tissue was respectively used to observe the changes of morphology, to determine the brain water content (BWC) by brain wet-to-dry weight ratio and to determine the expression of AQP4 by using immunohistochemical staining and to be semiquantified as an optical density (OD) value of positive cells with pathology imaging analysis system (PIAS).Results:In control group, there were no significant changes of the morphology, both the brain water content and the the expression of AQP4. In SE group, HE staining showed swelling, degeneration of the brain cell and proliferation of astrocyte, so did the changes of SE+GM1 group. Compared with control, SE group significantly increased BWC and the expression of AQP4, all began at 6h (P<0.05) and peaked at 72h (P<0.05), but no variance at 7d (P>0.05). AQP4 expression positively correlated with BWC (r=0.623, p<0.01). In SE+GM1 group, compared with SE group, the elevation of BWC was strongly attenuated at all time point except 7d. While AQP4 levels demonstrated an obviously atenuationfrom 24h. At 72 h, the AQP4 OD value decreased from 0.396±0.026 (SE group) to 0.243±0.036 (SE+GM1 group) (P<0.05). Conclusions: Cerebral cortical AQP4 expression in developing rat is up-regulated after SE with the deterioration of brain edema.It reveals AQP4 participates the development of brain edema after SE. Exogenous GM1 can inhibit AQP4 expression after SE and attenuate brain edema. |
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