Prenatal alcohol alters inflammatory signatures in enteric portal tissues following adult-onset cerebrovascular ischemic stroke

Prenatal alcohol exposure (PAE) impairs recovery from cerebrovascular ischemic stroke in adult rodents. Since the gut becomes dysbiotic following stroke, we assessed links between PAE and enteric portal inflammation. Adult control and PAE rat offspring received a unilateral endothelin-1-induced occlusion of the middle cerebral artery. Post-stroke behavioral disabilities and brain cytokines were assessed. Mesenteric adipose and liver transcriptomes were assessed from stroke-exposed and stroke-naive offspring. We identified, in the liver of stroke-naive animals, a moderate correlation between PAE and a gene network for inflammatory necroptosis. PAE inhibited the acute-phase brain inflammatory cytokine response to stroke. Post-stroke neurological function was correlated with an adipose gene network associated with B-lymphocyte differentiation and nuclear factor κB (NF-κB) signaling and with a liver pro-inflammatory gene network. Collectively, PAE inhibits brain inflammation but results in an inflammatory signature in enteric portal tissues after stroke, suggesting that PAE persistently and adversely impacts the gut-brain axis following adult-onset disease. [Display omitted] •Prenatal alcohol exposure (PAE) exacerbates effects of acute adult-onset disease•PAE promotes basal inflammatory necroptosis in adult liver•PAE inhibits brain cytokine response to cerebrovascular ischemic stroke in adults•PAE elevates inflammatory gene networks in enteric portal tissues after stroke Biological sciences; Developmental neuroscience; Neuroscience; Physiology