Journal Article

mCRP-Associated Vascular Pathophysiology in Progression and Outcome of Intracerebral Hemorrhage

Slevin, Mark, Șalari, Gabriela

2025

Overview

Monomeric C-reactive protein (mCRP), derived from the dissociation of the native pentameric CRP (pCRP), has been implicated in the pathophysiology of various neurological conditions, particularly intracerebral hemorrhage (ICH) and neurodegenerative diseases. mCRP accumulates in the brain after hemorrhagic stroke, contributing to the formation of the metabolic penumbra and promoting inflammation. Recent studies have linked mCRP to the activation of microglia, endothelial cells, and complement pathways, which collectively intensify neuroinflammation and disrupt tissue repair mechanisms. Additionally, mCRP is associated with cognitive decline, particularly in ICH survivors, by promoting microvascular damage, neurodegeneration, and vascular instability. The presence of mCRP in distant regions of the brain, including the hypothalamus, suggests its potential role in spreading inflammation and exacerbating long-term neurological damage. This review synthesizes findings on the pathogenic role of mCRP in stroke and neurodegeneration, proposing that mCRP could serve as both a biomarker and a therapeutic target for improving outcomes in stroke patients. Emerging immunopharmacological strategies are being actively pursued to mitigate the pathogenic activity of mCRP, a potent pro-inflammatory effector implicated in a variety of immune-mediated and neuroinflammatory conditions. These approaches encompass the inhibition of native pentameric CRP dissociation into its monomeric isoform, the disruption of mCRP’s high-affinity interactions with lipid rafts and cell surface receptors involved in innate immune activation, and the enhancement of its clearance through mechanisms such as solubilization, opsonin-mediated tagging, and phagocytic engagement. Targeting these immunoregulatory pathways offers a compelling therapeutic framework for attenuating mCRP-driven inflammatory cascades in both systemic and CNS-specific pathologies.

• Publisher: MDPI AG
• Subject: Animals / Atherosclerosis / Binding sites / Biomarkers / Biomarkers - metabolism / Brain - metabolism / Brain - pathology / C-reactive protein / C-Reactive Protein - metabolism / Cerebral Hemorrhage - metabolism / Cerebral Hemorrhage - pathology / Cerebral Hemorrhage - physiopathology / Cerebrovascular disease / Cholesterol / Development and progression / Disease Progression / Diseases / Edema / Endothelium / Enzymes / Health aspects / Hemorrhage / Humans / Inflammation / Inflammation - metabolism / Intracerebral hemorrhage / Ischemia / Kinases / Lipids / Mortality / Neurophysiology / Pathogenesis / Pathology / Pathophysiology / Proteins / Signal transduction / Stroke / Thrombosis