Systemic immune activation shapes stroke outcome.

Stroke is a major cause of morbidity and mortality, and activation of the immune system can impact on stroke outcome. Although the majority of research has focused on the role of the immune system after stroke there is increasing evidence to suggest that inflammation and immune activation prior to brain injury can influence stroke risk and outcome. With the high prevalence of co-morbidities in the Western world such as obesity, hypertension and diabetes, pre-existing chronic 'low-grade' systemic inflammation has become a customary characteristic of stroke pathophysiology that needs to be considered in the search for new therapies. The importance of the immune system in stroke has been demonstrated in a number of ways, both experimentally and in the clinical setting. This review will focus on the effect of immune activation arising from systemic inflammatory conditions and infection, how it affects the incidence and outcomes of stroke, and the possible underlying mechanisms involved. This article is part of a Special Issue entitled 'Neuroinflammation in neurodegeneration and neurodysfunction'.

Surgical manipulation compromises leukocyte mobilization responses and inflammation after experimental cerebral ischemia in mice.

Acute brain injury results in peripheral inflammatory changes, although the impact of these processes on neuronal death and neuroinflammation is currently unclear. To facilitate the translation of experimental studies to clinical benefit, it is vital to characterize the mechanisms by which acute brain injury induces peripheral inflammatory changes, and how these are affected by surgical manipulation in experimental models. Here we show that in mice, even mild surgical manipulation of extracranial tissues induced marked granulocyte mobilization (300%) and systemic induction of cytokines. However, intracranial changes induced by craniotomy, or subsequent induction of focal cerebral ischemia were required to induce egress of CXCR2-positive granulocytes from the bone marrow. CXCR2 blockade resulted in reduced mobilization of granulocytes from the bone marrow, caused an unexpected increase in circulating granulocytes, but failed to affect brain injury induced by cerebral ischemia. We also demonstrate that isoflurane anaesthesia interferes with circulating leukocyte responses, which could contribute to the reported vascular and neuroprotective effects of isoflurane. In addition, no immunosuppression develops in the bone marrow after experimental stroke. Thus, experimental models of cerebral ischemia are compromised by surgery and anaesthesia in proportion to the severity of surgical intervention and overall tissue injury. Understanding the inherent confounding effects of surgical manipulation and development of new models of cerebral ischemia with minimal surgical intervention could facilitate better understanding of interactions between inflammation and brain injury.