Journal Article

Dietary salt promotes ischemic brain injury and is associated with parenchymal migrasome formation

Klotz, Luisa, Minnerup, Jens, Schmidt-Pogoda, Antje, Strecker, Jan-Kolja, Breuer, Johanna, Beuker, Carolin, Hansen, Uwe, Massoth, Christina, Schwab, Nicholas, König, Simone, Bock, Stefanie, Liebmann, Marie, Wiendl, Heinz, Albrecht, Sarah, Sommer, Clemens

2018

Overview

Sodium chloride promotes vascular fibrosis, arterial hypertension, pro-inflammatory immune cell polarization and endothelial dysfunction, all of which might influence outcomes following stroke. But despite enormous translational relevance, the functional importance of sodium chloride in the pathophysiology of acute ischemic stroke is still unclear. In the current study, we show that high-salt diet leads to significantly worse functional outcomes, increased infarct volumes, and a loss of astrocytes and cortical neurons in acute ischemic stroke. While analyzing the underlying pathologic processes, we identified the migrasome as a novel, sodium chloride-driven pathomechanism in acute ischemic stroke. The migrasome was previously described in vitro as a migrating organelle, which incorporates and dispatches cytosol of surrounding cells and plays a role in intercellular signaling, whereas a pathophysiological meaning has not been elaborated. We here confirm previously reported characteristics of the migrasome in vivo. Immunohistochemistry, electron microscopy and proteomic analyses further demonstrate that the migrasome incorporates and dispatches cytosol of surrounding neurons following stroke. The clinical relevance of these findings is emphasized by neuropathological examinations, which detected migrasome formation in infarcted brain parenchyma of human stroke patients. In summary, we demonstrate that high-salt diet aggravates stroke outcomes, and we characterize the migrasome as a novel mechanism in acute stroke pathophysiology.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animals / Astrocytes / Astrocytes - metabolism / Astrocytes - pathology / Biology and Life Sciences / Brain / Brain injuries / Brain Injuries - metabolism / Brain Injuries - pathology / Brain Injuries - physiopathology / Brain injury / Brain Ischemia - metabolism / Brain Ischemia - pathology / Brain Ischemia - physiopathology / Care and treatment / Cell adhesion & migration / Cerebral Cortex - metabolism / Cerebral Cortex - pathology / Cerebral Cortex - physiopathology / Chloride / Chlorine compounds / Cytosol / Cytosol - metabolism / Cytosol - pathology / Diet / Drinking water / Electron microscopy / Fibrosis / Head injuries / Health aspects / Hypertension / Immune system / Immunohistochemistry / Inflammation / Ischemia / Male / Medicine and Health Sciences / Mice / Nervous system / Neurology / Neurons / Neurons - metabolism / Neurons - pathology / Organelles - metabolism / Organelles - pathology / Parenchyma / Physical Sciences / Proteomics / Risk factors / Rodents / Salt / Salt (Food) / Salts / Sodium / Sodium chloride / Sodium Chloride, Dietary - adverse effects / Sodium Chloride, Dietary - pharmacology / Stem cells / Stroke / Stroke - metabolism / Stroke - pathology / Stroke - physiopathology