Perspectives on effect of spleen in ischemic stroke

Abstract

Despite decades of research, stroke therapies are limited to recanalization therapies that can only be used on <10% of stroke patients; the vast majority of stroke patients cannot be treated by these methods. Even if recanalization is successful, the outcome is often poor due to subsequent reperfusion injury. A major damage mechanism operating in stroke is inflammatory injury due to excessive pro-inflammatory cascades. Many studies have shown that, after stroke, splenic inflammatory cells, including neutrophils, monocytes/macrophages, and lymphocytes, are released and infiltrate the brain, heightening brain inflammation, and exacerbating ischemia/reperfusion injury. Clinical studies have observed spleen contraction in acute stroke patients where functional outcome improved with the gradual recovery of spleen volume. These observations are supported by stroke animal studies that have used splenectomy- or radiation-induced inhibition of spleen function to show spleen volume decrease during the acute phase of middle cerebral artery occlusion, and transfer of splenocytes to stroke-injured brain areas. Thus, activation and release of splenic cells are upstream of excessive brain inflammation in stroke. The development of reversible means of regulating splenic activity offers a therapeutic target and potential clinical treatment for decreasing brain inflammation and improving stroke outcomes.

Modulation of NLRP3 inflammasome-related-inflammation via RIPK1/RIPK3-DRP1 or HIF-1α signaling by phenothiazine in hypothermic and normothermic neuroprotection after acute ischemic stroke

“…This complex activates DRP1 through phosphorylation at Ser616 in a RIPK3-dependent manner, a process that precipitates mitochondrial damage and ROS production [ 36 ]. The ROS act as stimulants for the activation of the NLRP3 inflammasome, a pivotal event in the inflammatory cascade following ischemic injury [ 37 , 38 ]. Our current findings support with emerging literature, which suggests the involvement of the RIPK1/RIPK3 complex in mitochondrial fission through DRP1, leading to activation of the NLRP3 inflammasome.…”

Bridging the Gap: Investigating the Link between Inflammasomes and Postoperative Cognitive Dysfunction

“…Inflammation is necessary for tissue healing and pathogen elimination, but it can be harmful if it is dysregulated or prolonged [22][23][24]. For instance, surgical trauma is an acute stress response to sterile injury induced by surgery; this causes inflammation that can disrupt the sympathetic nervous system, neuroendocrine system, and hypothalamus-pituitary-adrenal axis, leading to systemic inflammation and immune system dysfunction [25][26][27]. In addition, it is well known that inflammation is regulated by inflammasomes, which are multiprotein complexes involved in the control of innate immunity and have been linked to the etiology of numerous human disorders, including POCD [28][29][30][31][32][33][34][35].…”