Abstract
BackgroundVasogenic edema dynamically accumulates in many brain disorders associated with brain inflammation, with the critical step of edema exacerbation feared in patient care. Water entrance through blood-brain barrier (BBB) opening is thought to have a role in edema formation. Nevertheless, the mechanisms of edema resolution remain poorly understood. Because the water channel aquaporin 4 (AQP4) provides an important route for vasogenic edema resolution, we studied the time course of AQP4 expression to better understand its potential effect in countering the exacerbation of vasogenic edema.MethodsFocal inflammation was induced in the rat brain by a lysolecithin injection and was evaluated at 1, 3, 7, 14 and 20 days using a combination of in vivo MRI with apparent diffusion coefficient (ADC) measurements used as a marker of water content, and molecular and histological approaches for the quantification of AQP4 expression. Markers of active inflammation (macrophages, BBB permeability, and interleukin-1β) and markers of scarring (gliosis) were also quantified.ResultsThis animal model of brain inflammation demonstrated two phases of edema development: an initial edema build-up phase during active inflammation that peaked after 3 days (ADC increase) was followed by an edema resolution phase that lasted from 7 to 20 days post injection (ADC decrease) and was accompanied by glial scar formation. A moderate upregulation in AQP4 was observed during the build-up phase, but a much stronger transcriptional and translational level of AQP4 expression was observed during the secondary edema resolution phase.ConclusionsWe conclude that a time lag in AQP4 expression occurs such that the more significant upregulation was achieved only after a delay period. This change in AQP4 expression appears to act as an important determinant in the exacerbation of edema, considering that AQP4 expression is insufficient to counter the water influx during the build-up phase, while the second more pronounced but delayed upregulation is involved in the resolution phase. A better pathophysiological understanding of edema exacerbation, which is observed in many clinical situations, is crucial in pursuing new therapeutic strategies.
Highlights
Vasogenic edema dynamically accumulates in many brain disorders associated with brain inflammation, with the critical step of edema exacerbation feared in patient care
Because brain inflammation occurs in a phasic manner, water entrance secondary to inflammation is thought to contribute to the ongoing clinical exacerbation that is observed following stroke, trauma or encephalitis [6]
We found the more significant transcriptional and translational upregulation of aquaporin 4 (AQP4) only during the edema resolution phase, with AQP4 being potentially insufficient to counter the excess water accumulation that occurs during the initial edema build-up phase
Summary
Vasogenic edema dynamically accumulates in many brain disorders associated with brain inflammation, with the critical step of edema exacerbation feared in patient care. Vasogenic edema is a highly dynamic process with phases of significant water accumulation and subsequent reduction. Edema fluid can be cleared into the cerebrospinal fluid (CSF) in the subarachnoid space or ventricles, or it can be cleared back into the blood [7] All of these exit routes strongly express the selective water channel transporter aquaporin 4 (AQP4) [8]. Experiments that were conducted on AQP4-null mice have shown that AQP4dependent transmembrane movements into the CSF and blood are dominant mechanisms for clearing excess brain water in vasogenic edema [9,10,11]. A precise temporal course of this AQP4 upregulation during the build-up and resolution phases in the dynamic evolution of vasogenic edema in vivo is still lacking
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
