RT Journal Article
T1 Aquaporin-4 Mediates Permanent Brain Alterations in a Mouse Model of Hypoxia-Aged Hydrocephalus
A1 Trillo-Contreras, José Luis
A1 Toledo-Aral, Juan José
A1 Villadiego, Javier
A1 Echevarría, Miriam
K1 AQP4
K1 Astrocytes
K1 Hypoxia
K1 Hydrocephalus
K1 Cerebrospinal fluid
K1 Cerebral ventricles
K1 Homeostasis
K1 Drainage
K1 Acuaporina 4
K1 Astrocitos
K1 Hipoxia
K1 Hidrocefalia
K1 Líquido cefalorraquídeo
K1 Ventrículos cerebrales
K1 Drenaje
AB Aquaporin-4 (AQP4) is the principal water channel in the brain being expressed in astrocytes and ependymal cells. AQP4 plays an important role in cerebrospinal fluid (CSF) homeostasis, and alterations in its expression have been associated with hydrocephalus. AQP4 contributes to the development of hydrocephalus by hypoxia in aged mice, reproducing such principal characteristics of the disease. Here, we explore whether these alterations associated with the hydrocephalic state are permanent or can be reverted by reexposure to normoxia. Alterations such as ventriculomegaly, elevated intracranial pressure, and cognitive deficits were reversed, whereas deficits in CSF outflow and ventricular distensibility were not recovered, remaining impaired even one month after reestablishment of normoxia. Interestingly, in AQP4-/- mice, the impairment in CSF drainage and ventricular distensibility was completely reverted by re-normoxia, indicating that AQP4 has a structural role in the chronification of those alterations. Finally, we show that aged mice subjected to two hypoxic episodes experience permanent ventriculomegaly. These data reveal that repetitive hypoxic events in aged cerebral tissue promote the permanent alterations involved in hydrocephalic pathophysiology, which are dependent on AQP4 expression.
PB MDPI
YR 2021
FD 2021-09-09
LK http://hdl.handle.net/10668/4403
UL http://hdl.handle.net/10668/4403
LA en
NO Trillo-Contreras JL, Toledo-Aral JJ, Villadiego J, Echevarría M. Aquaporin-4 Mediates Permanent Brain Alterations in a Mouse Model of Hypoxia-Aged Hydrocephalus. Int J Mol Sci. 2021 Sep 9;22(18):9745
DS RISalud
RD Apr 18, 2025