Down-regulated expression of aquaporin-4 in the cerebellum after status epilepticus

Abstract

Status epilepticus (SE) is a common neurological condition associated with high rates of mortality and permanent brain injury. SE usually leads to neuronal death which may be accompanied by edema, epileptogenesis and learning impairment. Aquaporin-4 (AQP4), is a transmembrane water channel protein in the neuropil of the central nervous system that has an important role in water transport in the brain; AQP4 expression is altered in many pathological conditions such as changes in the blood- brain barrier and/or astrocytic activation, including seizures. AQP4 was shown to be downregulated in the piriform cortex and the hippocampus after SE. Although it is normally expressed at a high level in the cerebellum, little is known about AQP4 levels in the cerebellum following SE. We addressed this in the present study in a mouse model of pilocarpine-induced SE. We found that AQP4 expression was reduced from 3 h to 3 days after SE, with the levels recovering on day 7. Moreover, mice in the acute post-SE stages exhibited impaired motor coordination and learning. These results indicate that cerebellar damage following SE involves changes in AQP4 expression.

The Effect of Aquaporin-4 Knockout on Interstitial Fluid Flow and the Structure of the Extracellular Space in the Deep Brain

“…It is of great significance for the balance of water within the intercellular space and the realization of brain function [ 24 ]. AQP4 primarily localizes to the subpial astrocyte processes, the perivascular astrocyte endfeet, the basolateral membrane of ependymal cells, and subependymal astrocyte processes [ 2 , 23 , 25 - 27 ]. Normally, water molecules enter the cell facilitated by AQP4, causing astrocyte swelling and ECS volume reduction [ 23 ].…”