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Publication : Aquaporin-4 Mediates Permanent Brain Alterations in a Mouse Model of Hypoxia-Aged Hydrocephalus.

First Author  Trillo-Contreras JL Year  2021
Journal  Int J Mol Sci Volume  22
Issue  18 PubMed ID  34575909
Mgi Jnum  J:323010 Mgi Id  MGI:6766208
Doi  10.3390/ijms22189745 Citation  Trillo-Contreras JL, et al. (2021) Aquaporin-4 Mediates Permanent Brain Alterations in a Mouse Model of Hypoxia-Aged Hydrocephalus. Int J Mol Sci 22(18)
abstractText  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.
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