Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases
essential_information
- Person in charge：Kaibin Shi
- Data Sources： OTHERS
- Number of papers：OTHERS20190895
- Published time：2019-07-08
2019-07-08
Published articles
Journal：The Lancet Neurology
Publication type: Review
IF(IF): 28.755
PMID: 31296369 Link To Pubmed Full text Download
Background And Purpose
Stroke, including acute ischaemic stroke and intracerebral haemorrhage, results in neuronal cell death and the release of factors such as damage-associated molecular patterns (DAMPs) that elicit localised inflammation in the injured brain region. Such focal brain inflammation aggravates secondary brain injury by exacerbating blood–brain barrier damage, microvascular failure, brain oedema, oxidative stress, and by directly inducing neuronal cell death. In addition to inflammation localised to the injured brain region, a growing body of evidence suggests that inflammatory responses after a stroke occur and persist throughout the entire brain. In this Personal View, we describe the development of global brain inflammation in stroke according to existing evidence and contrast the salient features of global brain inflammation relative to focal brain inflammation to understand its provenance and the potential effects on clinical outcome. Finally, we discuss the role of future research in understanding the biological underpinnings of global brain inflammation to inform potential development of a rationalised immune intervention as a primary or adjunctive approach to treat stroke.
Method
We searched PubMed for articles published mostly between Jan 1, 2013, and May 31, 2018. We used the terms “inflammation”, “neuroinflammation”, “immune”, “immunity”, “ischaemic stroke”, “cerebral ischaemia”, “haemorrhagic stroke”, and “intracerebral haemorrhage”. We used English search words, but also included papers published in other languages with English abstracts. We selected articles describing clinical and animal model findings on inflammation of stroke.
Conclusion
Despite the different primary injury mechanisms, inflammation is triggered through a common pathway shared by both acute ischaemic stroke and intracerebral haemorrhage, and plays a crucial part in the development of brain oedema and other pathophysiological consequences. Additionally, the evidence reviewed here presents a complex picture of inflammatory responses in the injured brain that are not restricted to the site of injury but which can occur globally and persist in the long term. Future research must not only aim to understand how global brain inflammation is initiated and maintained but also clarify the role of global brain inflammation in the long-term sequelae of stroke and its roles in neurological recovery and brain tissue regeneration. These efforts would clear the way for designing immune modulatory therapies to curtail inflammation-associated secondary brain injury. Previous efforts to manipulate the immune system involved targeting adhesion molecules (ie, natalizumab), cell egress ability (ie, fingolimod), or cytokines in the periphery. These approaches prevent further fuelling of inflammation but do not alter ongoing in-situ processes. Direct interference of molecules that trigger brain inflammation locally is likely to curb injury expansion within the brain. The successful management of patients with stroke might require coupling of focal and systemic approaches to modulate brain inflammation.
Main results
Evidence derived from studies in humans and animal models of stroke increasingly suggests that immune responses occur in areas remote from the injury site in both acute and chronic phases of stroke. Global brain inflammation features similar cellular and molecular components as focal brain inflammation, but global brain inflammation evolves in a distinct profile. These evidence including global distribution of activated glial cells, especially microglia, and peripheral leukocytes including myeloid cells and lymphocytes, as well as the global activating of microvessel endothelial cells associated with blood brain barrier leakage. Global brain inflammation might continuously shape the evolving pathology after a stroke and affect the patients’ long-term neurological outcome.