Platelets, Thromboinflammation and Neurovascular Disease

Abstract

The brain and spinal cord are immune-privileged organs, but in the disease state protection mechanisms such as the blood brain barrier (BBB) are ineffective or overcome by pathological processes. In neuroinflammatory diseases, microglia cells and other resident immune cells contribute to local vascular inflammation and potentially a systemic inflammatory response taking place in parallel. Microglia cells interact with other cells impacting on the integrity of the BBB and propagate the inflammatory response through the release of inflammatory signals. Here, we discuss the activation and response mechanisms of innate and adaptive immune processes in response to neuroinflammation. Furthermore, the clinical importance of neuroinflammatory mediators and a potential translational relevance of involved mechanisms are addressed also with focus on non-classical immune cells including microglia cells or platelets. As illustrative examples, novel agents such as Anfibatide or Revacept, which result in reduced recruitment and activation of platelets, a subsequently blunted activation of the coagulation cascade and further inflammatory process, demonstrating that mechanisms of neuroinflammation and thrombosis are interconnected and should be further subject to in depth clinical and basic research.

Exploring the utility of a latent variable as comprehensive inflammatory prognostic index in critically ill patients with cerebral infarction

“…Inflammation is a key mechanism in stroke, and the post-stroke inflammatory response plays a vital role in secondary brain injury and activation of coagulation ( 33 , 34 ). The disruption of normal coagulation processes after cerebral infarction can lead to exacerbated ischemic damage in the brain, and also activate multiple inflammatory pathways ( 35 ). The changes in peripheral blood indicators like neutrophils, lymphocytes, monocytes, and platelets are sensitive markers of the body’s cascade response to cerebral infarction, especially in the presence of severe complications and comorbidities ( 36 , 37 ).…”

Circulating Blood Prognostic Biomarker Signatures for Hemorrhagic Cerebral Cavernous Malformations (CCMs)

“…Among identified candidate prognostic biomarkers, plasma kallikrein (PKa) is involved in blood coagulation, fibrinolysis, hemostasis, and inflammatory response [45][46][47][48]. PKa deficiency due to KLKB1 mutations leads to vascular bleeding and has been implicated in hereditary angioedema and hemorrhagic stroke [47,[49][50][51][52][53][54][55].…”

“…Among identified candidate prognostic biomarkers, plasma kallikrein (PKa) is involved in blood coagulation, fibrinolysis, hemostasis, and inflammatory response [45][46][47][48]. PKa deficiency due to KLKB1 mutations leads to vascular bleeding and has been implicated in hereditary angioedema and hemorrhagic stroke [47,[49][50][51][52][53][54][55]. Serpins, a superfamily of serine protease inhibitors, play critical roles in vascular angiogenesis and have been implicated in retinal vascular leakage and hemorrhagic stroke [56][57][58][59][60][61][62][63].…”

The Multiple Sclerosis Modulatory Potential of Natural Multi-Targeting Antioxidants

“…The CD4+ T-helper (Th) cells, and especially Th1 and Th17, signal the production of autoantibodies, via the induction of B lymphocytes, decreasing the ratio between T and B lymphocytes, with CD4+, CD8+ and natural killer cells up-regulating the immune responses, whilst regulatory T cells (T-regs), inhibiting the T and B cells, derived autoimmune responses [ 7 ]. Various types of leucocytes may increase BBB permeability by stimulating various peripheral cells, such as platelets [ 8 ]. Myelin reactive CD4+ T cells perform a key role in demyelination, after their migration into the CNS, whilst naive T lymphocytes maturation to Th1 and Th17 are another myelin specific deterioration mechanism, secreting pro-inflammatory cytokines, with antigen presentation, via major histocompatibility complex II, on dendritic cells, being the main T-cell activation mechanism [ 9 ].…”