The Demise of the Blood-Brain Barrier in Amyotrophic Lateral Sclerosis and the Role of Astrocytes

Abstract

Combined MRI and immunofluorescence studies on the brain of the transgenic hSOD1 G93A ALS rat model reveled astrogliosis near dilated lateral ventricles and blood-brain barrier (BBB) compromise. It was thus of particular interest to check the expression of glial aquaporins known to be specifically present in the astroglial endfeet of the BBB. Immunoflu-orescence revealed a more abundant expression of aquaporin 4 (AQP4) in the brainstem and cerebral cortex of ALS rats. Immunogold EM studies also revealed a supramolecular change in the distribution of AQP4 in astrocytic endfeet ensheathing blood vessels. A reverse expression was also observed for astrocytic AQP4 versus the Kir 4.1 channel-the two proteins known to form aggregates. Preliminary electrophysiological data on astrocytes in culture showed a different behavior of the Kir current as compared to the wild type. Thus, a role of glia in the demise of the BBB in the ALS brain was suggested with the AQP4 and Kir4. 1 complex being the molecular target for possible therapies.