First published January 28, 2020 - More info
Alcohol abuse is a major public health problem worldwide causing a wide range of preventable morbidity and mortality. In this translational study, we show that heavy drinking (HD) (≥6 standard drinks/day) is independently associated to a worse outcome of ischemic stroke patients. To study the underlying mechanisms of this deleterious effect of HD, we then performed an extensive analysis of the brain inflammatory responses of mice exposed or not to 10% alcohol before and after ischemic stroke. Inflammatory responses were analyzed at the parenchymal, perivascular and vascular levels by using transcriptomic, immunohistochemical, in vivo two-photon microscopy and molecular MRI analyses. Alcohol-exposed mice show, in the absence of any other insult, a neurovascular inflammatory priming [i.e., an abnormal inflammatory status including an increase in brain perivascular macrophages (PVM)] associated to exacerbated inflammatory responses after a secondary insult (ischemic stroke or LPS challenge). Similar to our clinical data, alcohol-exposed mice showed larger ischemic lesions. We show here that PVM are key players on this aggravating effect of alcohol, since their specific depletion blocks the alcohol-induced aggravation of ischemic lesions. This study opens new therapeutic avenues aiming at blocking alcohol-induced exacerbation of the neurovascular inflammatory responses triggered after ischemic stroke.