Immune responses in stroke: how the immune system contributes to damage and healing after stroke and how this knowledge could be translated to better cures?

Abstract

Stroke is one of the leading causes of death and disability worldwide. The long-standing dogma that stroke is exclusively a vascular disease has been questioned by extensive clinical findings of immune factors that are associated mostly with inflammation after stroke. These have been confirmed in preclinical studies using experimental animal models. It is now accepted that inflammation and immune mediators are critical in acute and long-term neuronal tissue damage and healing following thrombotic and ischaemic stroke. Despite mounting information delineating the role of the immune system in stroke, the mechanisms of how inflammatory cells and their mediators are involved in stroke-induced neuroinflammation are still not fully understood. Currently, there is no available treatment for targeting the acute immune response that develops in the brain during cerebral ischaemia. No new treatment has been introduced to stroke therapy since the discovery of tissue plasminogen activator therapy in 1996. Here, we review current knowledge of the immunity of stroke and identify critical gaps that hinder current therapies. We will discuss advances in the understanding of the complex innate and adaptive immune responses in stroke; mechanisms of immune cell-mediated and factor-mediated vascular and tissue injury; immunity-induced tissue repair; and the importance of modulating immunity in stroke.

IL‐2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8+ T cells

“…The above protection of white matter may be closely related to the suppression of the poststroke adaptive immune system. Stroke elicits profound activation of peripheral immune system and infiltration of peripheral immune cells into the brain . Acute immune interventions that avoid over‐activation of peripheral immune cells reduce immune cell‐mediated neuronal cell injury and attenuate subsequent poststroke immunosuppression .…”

Post-Ischaemic Immunological Response in the Brain: Targeting Microglia in Ischaemic Stroke Therapy

“…Microglia, comprising~10% of cells in the brain, are the resident mononuclear phagocytes of the CNS with critical roles in initiating innate and adaptive immune responses [22,23]. Microglia also contribute to the maintenance of homeostasis within the CNS, including promoting neuronal survival and mediating synaptic plasticity [24,25].…”

Oxygen metabolism MRI – A comparison with perfusion imaging in a rat model of MCA branch occlusion and reperfusion

“…The neuroinflammatory reaction after AIS is a substantial component of the secondary injuries that occur in the days and weeks that follow the ischemic insult (108,137). The activation of microglia will entail a transformation from the ramified morphology, inherent to resting cells, to the large so-called amoeboid type which is hard to differentiate from those macrophages that enter the brain and which perform the debridement of necrotic tissue.…”

“…Activation of microglia can be described as a double edge sword; beneficial effects such as the debridement of necrotic tissue and the promotion of large-scale tissue repair are counteracted by the production of proinflammatory mediators linked to a worsening of brain injury through the destruction of the neurovascular unit, as well as contributing to neuronal death by promoting apoptosis (137). The possibility to better monitor and diagnose inflammatory progression is a long-standing objective in experimental as well as clinical AIS research.…”