Complex interplay of multiple biological systems that contribute to post-stroke infections

Stroke is a leading contributor of death and disability around the world. Despite its recognised debilitating neurological deficits, a devastating clinical complication of surviving stroke patients that needs more attention is infection. Up to half of the patients develop infections after stroke, and a high proportion of them will die as a direct consequence. Major clinical trials that examined preventive antibiotic therapy in stroke patients have demonstrated this method of prevention is not effective as it does not reduce incidence of post-stroke pneumonia or improve patient outcome. Additionally, retrospective studies evaluating the use of β-blockers for the modulation of the sympathetic nervous system to prevent post-stroke infections have given mixed results. Therefore, there is an urgent need for more effective therapeutic options that target the underlying mechanisms of post-stroke infections. The understanding that infections are largely attributable to the “stroke-induced systemic immunosuppression” phenomenon has begun to emerge, and thus, exploring the pathways that trigger post-stroke immunosuppression is expected to reveal potential new therapeutics. As such, we will outline the impacts that stroke has on several biological systems in this review, and discuss how these contribute to host susceptibility to infection after stroke. Furthermore, the emerging role of the gut and its microbiota has recently come to surface and intensifies the complex pathways to post-stroke infection. Finally, we identify potential avenues to combat infection that target the pathways of stroke-induced systemic immunosuppression to ultimately improve stroke patient outcome.