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Differences in the post-stroke innate immune response between young and old
AbstractAging is associated to progressive changes impairing fundamental cellular and tissue functions, and the relationships amongst them through the vascular and immune systems. Aging factors are key to understanding the pathophysiology of stroke since they increase its risk and worsen its functional outcome. Most currently recognised hallmarks of aging are also involved in the cerebral responses to stroke. Notably, age-associated chronic low-grade inflammation is related to innate immune responses highlighted by induction of type-I interferon. The interferon program is prominent in microglia where it interrelates cell d...
Source: Seminars in Immunopathology - April 12, 2023 Category: Pathology Source Type: research

Regulatory T lymphocytes as a therapy for ischemic stroke
AbstractUnrestrained excessive inflammatory responses exacerbate ischemic brain injury and impede post-stroke brain recovery. CD4+CD25+Foxp3+ regulatory T (Treg) cells play important immunosuppressive roles to curtail inflammatory responses and regain immune homeostasis after stroke. Accumulating evidence confirms that Treg cells are neuroprotective at the acute stage after stroke and promote brain repair at the chronic phases. The beneficial effects of Treg cells are mediated by diverse mechanisms involving cell –cell interactions and soluble factor release. Multiple types of cells, including both immune cells and non-i...
Source: Seminars in Immunopathology - December 5, 2022 Category: Pathology Source Type: research

Sex differences in the inflammatory response to stroke
AbstractIschemic stroke is a leading cause of morbidity and mortality and disproportionally affects women, in part due to their higher longevity. Older women have poorer outcomes after stroke with high rates of cognitive deficits, depression, and reduced quality of life. Post-stroke inflammatory responses are also sexually dimorphic and drive differences in infarct size and recovery. Factors that influence sex-specific immune responses can be both intrinsic and extrinsic. Differences in gonadal hormone exposure, sex chromosome compliment, and environmental/social factors can drive changes in transcriptional and metabolic p...
Source: Seminars in Immunopathology - November 10, 2022 Category: Pathology Source Type: research

The immunopathology of B lymphocytes during stroke-induced injury and repair
AbstractB cells, also known as B lymphocytes or lymphoid lineage cells, are a historically understudied cell population with regard to brain-related injuries and diseases. However, an increasing number of publications have begun to elucidate the different phenotypes and roles B cells can undertake during central nervous system (CNS) pathology, including following ischemic and hemorrhagic stroke. B cell phenotype is intrinsically linked to function following stroke, as they may be beneficial or detrimental depending on the subset, timing, and microenvironment. Factors such as age, sex, and presence of co-morbidity also infl...
Source: Seminars in Immunopathology - November 29, 2022 Category: Pathology Source Type: research

The role of the ATP-adenosine axis in ischemic stroke
AbstractIn ischemic stroke, the primary neuronal injury caused by the disruption of energy supply is further exacerbated by secondary sterile inflammation. The inflammatory cascade is largely initiated by the purine adenosine triphosphate (ATP) which is extensively released to the interstitial space during brain ischemia and functions as an extracellular danger signaling molecule. By engaging P2 receptors, extracellular ATP activates microglia leading to cytokine and chemokine production and subsequent immune cell recruitment from the periphery which further amplifies post-stroke inflammation. The ectonucleotidases CD39 an...
Source: Seminars in Immunopathology - March 14, 2023 Category: Pathology Source Type: research

The role of circulating cell-free DNA as an inflammatory mediator after stroke
We report the current understanding for mechanisms of DNA uptake and sensing in the context of post-stroke inflammation. Moreover, we compare possible treatment options targeting cell-free DNA, DNA-sensing pathways, and the downstream mediators. Finally, we describe clinical implications of this inflammatory pathway for stroke patients, open questions, and potential future research directions.
Source: Seminars in Immunopathology - May 22, 2023 Category: Pathology Source Type: research

Systemic innate myeloid responses to acute ischaemic and haemorrhagic stroke
AbstractAcute ischaemic and haemorrhagic stroke account for significant disability and morbidity burdens worldwide. The myeloid arm of the peripheral innate immune system is critical in the immunological response to acute ischaemic and haemorrhagic stroke. Neutrophils, monocytes, and dendritic cells (DC) contribute to the evolution of pathogenic local and systemic inflammation, whilst maintaining a critical role in ongoing immunity protecting against secondary infections. This review aims to summarise the key alterations to myeloid immunity in acute ischaemic stroke, intracerebral haemorrhage (ICH), and subarachnoid haemor...
Source: Seminars in Immunopathology - November 8, 2022 Category: Pathology Source Type: research

Inflammatory Responses After Ischemic Stroke
AbstractIschemic stroke generates an immune response that contributes to neuronal loss as well as tissue repair. This is a complex process involving a range of cell types and effector molecules and impacts tissues outside of the CNS. Recent reviews address specific aspects of this response, but several years have passed and important advances have been made since a high-level review has summarized the overall state of the field. The present review examines the initiation of the inflammatory response after ischemic stroke, the complex impacts of leukocytes on patient outcome, and the potential of basic science discoveries t...
Source: Seminars in Immunopathology - June 29, 2022 Category: Pathology Source Type: research

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