| First Author | Yang B | Year | 2008 |
| Journal | J Biol Chem | Volume | 283 |
| Issue | 22 | Pages | 15280-6 |
| PubMed ID | 18375385 | Mgi Jnum | J:137574 |
| Mgi Id | MGI:3801247 | Doi | 10.1074/jbc.M801425200 |
| Citation | Yang B, et al. (2008) Glial cell aquaporin-4 overexpression in transgenic mice accelerates cytotoxic brain swelling. J Biol Chem 283(22):15280-6 |
| abstractText | Aquaporin-4 (AQP4) is a water transport protein expressed in glial cell plasma membranes, including glial cell foot processes lining the blood-brain barrier. AQP4 deletion in mice reduces cytotoxic brain edema produced by different pathologies. To determine whether AQP4 is rate-limiting for brain water accumulation and whether altered AQP4 expression, as occurs in various pathologies, could have functional importance, we generated mice that overexpressed AQP4 in brain glial cells by a transgenic approach using the glial fibrillary acid protein promoter. Overexpression of AQP4 protein in brain by approximately 2.3-fold did not affect mouse survival, appearance, or behavior, nor did it affect brain anatomy or intracranial pressure (ICP). However, following acute water intoxication produced by intraperitoneal water injection, AQP4-overexpressing mice had an accelerated progression of cytotoxic brain swelling, with ICP elevation of 20 +/- 2 mmHg at 10 min, often producing brain herniation and death. In contrast, ICP elevation was 14 +/- 2 mmHg at 10 min in control mice and 9.8 +/- 2 mmHg in AQP4 knock-out mice. The deduced increase in brain water content correlated linearly with brain AQP4 protein expression. We conclude that AQP4 expression is rate-limiting for brain water accumulation, and thus, that altered AQP4 expression can be functionally significant. |
