Immunomodulation after ischemic stroke: potential mechanisms and implications for therapy

Abstract

Brain injuries are often associated with intensive care admissions, and carry high morbidity and mortality rates. Ischemic stroke is one of the most frequent causes of injury to the central nervous system. It is now increasingly clear that human stroke causes multi-organ systemic disease. Brain inflammation may lead to opposing local and systemic effects. Suppression of systemic immunity by the nervous system could protect the brain from additional inflammatory damage; however, it may increase the susceptibility to infection. Pneumonia and urinary tract infection are the most common complications occurring in patients after stroke. The mechanisms involved in lung-brain interactions are still unknown, but some studies have suggested that inhibition of the cholinergic anti-inflammatory pathway and release of glucocorticoids, catecholamines, and damage-associated molecular patterns (DAMPs) are among the pathophysiological mechanisms involved in communication from the ischemic brain to the lungs after stroke. This review describes the modifications in local and systemic immunity that occur after stroke, outlines mechanisms of stroke-induced immunosuppression and their role in pneumonia, and highlights potential therapeutic targets to reduce post-stroke complications. Despite significant advances towards a better understanding of the pathophysiology of ischemic stroke-induced immunosuppression and stroke-associated pneumonia (SAP) in recent years, many unanswered questions remain. The true incidence and outcomes of SAP, especially in intensive care unit settings, have yet to be determined, as has the full extent of stroke-induced immunosuppression and its clinical implications.

Systemic inflammatory response syndrome, infection, and outcome in intracerebral hemorrhage

“…Use of anti-inflammatory or immunosuppressive treatments for SIRS, or any type of poststroke inflammatory response, is complicated by the potential for an increased risk of infection with immunosuppression. 31 In patients with both ischemic and hemorrhagic stroke, potential treatment options for poststroke inflammation include stem cells (by protecting neurons from immune cell–mediated apoptosis), therapeutic hypothermia, inhibition of microglial activation, minocycline, natalizumab, and fingolimod. 32 – 37 Treating poststroke inflammation is further complicated by the beneficial role of the immune response after stroke, as the immune response can aid in stroke recovery.…”

Transcriptomic Study Reveals Recovery of Impaired Astrocytes Contribute to Neuroprotective Effects of Danhong Injection Against Cerebral Ischemia/Reperfusion-Induced Injury

“…may last for a long period of time ( Hu et al, 2012 ). As a consequence, patients may suffer from neuron functional deficiency, as well as high risks for local or systemic inflammation ( Westendorp et al, 2011 ; Becker and Buckwalter, 2016 ; Santos Samary et al, 2016 ). Furthermore, it was recently identified that the gene expression patterns vary over the course of acute IRI ( Wang et al, 2017 ).…”

Frequencies of circulating B- and T-lymphocytes as indicators for stroke outcomes

“…They may also serve as biomarkers for infectious complications, such as pneumonia and urinary tract infection after stroke 11,12. Interestingly, recent clinical studies suggested that the changes in immune cell composition may impact the long-term outcome after brain injuries.…”