NLRP3-dependent lipid droplet formation contributes to posthemorrhagic hydrocephalus by increasing the permeability of the blood–cerebrospinal fluid barrier in the choroid plexus

Abstract

Hydrocephalus is a severe complication that can result from intracerebral hemorrhage, especially if this hemorrhage extends into the ventricles. Our previous study indicated that the NLRP3 inflammasome mediates cerebrospinal fluid hypersecretion in the choroid plexus epithelium. However, the pathogenesis of posthemorrhagic hydrocephalus remains unclear, and therapeutic strategies for prevention and treatment are lacking. In this study, an Nlrp3−/− rat model of intracerebral hemorrhage with ventricular extension and primary choroid plexus epithelial cell culture were used to investigate the potential effects of NLRP3-dependent lipid droplet formation and its role in the pathogenesis of posthemorrhagic hydrocephalus. The data indicated that NLRP3-mediated dysfunction of the blood–cerebrospinal fluid barrier (B-CSFB) accelerated neurological deficits and hydrocephalus, at least in part, through the formation of lipid droplets in the choroid plexus; these lipid droplets interacted with mitochondria and increased the release of mitochondrial reactive oxygen species that destroyed tight junctions in the choroid plexus after intracerebral hemorrhage with ventricular extension. This study broadens the current understanding of the relationship among NLRP3, lipid droplets and the B-CSFB and provides a new therapeutic target for the treatment of posthemorrhagic hydrocephalus. Strategies to protect the B-CSFB may be effective therapeutic approaches for posthemorrhagic hydrocephalus.

Peripheral cytokine interleukin‐10 alleviates perihematomal edema after intracerebral hemorrhage via interleukin‐10 receptor/JAK1/STAT3 signaling

“…Immunofluorescence staining of cryosections from frozen brain specimens was conducted in accordance with previously reported procedures. 14 Specifically, 3 days post‐ICH, the mice were subjected to deep anesthesia followed by intravenous administration of NS and 4% paraformaldehyde. The brains were promptly excised, fixed in 4% paraformaldehyde for 24 h, and then immersed in 30% sucrose for 72 h for cryoprotection.…”

“…Western blot analysis was conducted in accordance with previously established protocols. 8 , 13 , 14 Tissue samples surrounding the hematoma were harvested and homogenized, and a protein extraction kit (BC3710; Solarbio; Beijing, China) was used to extract total protein. Throughout the procedure, the temperature was strictly controlled to preserve protein integrity.…”

Neutrophil extracellular trap-mediated impairment of meningeal lymphatic drainage exacerbates secondary hydrocephalus after intraventricular hemorrhage

“…To comprehensively evaluate neurological function, including balance, sensory, and motor functions, we used the mNSS [18]. A scale ranging from 0 to 18 was used to grade neurological function, and the scores indicated different levels of injury severity, such as more severe (13)(14)(15)(16)(17)(18), moderate (7)(8)(9)(10)(11)(12), or mild (1-6) injury.…”

“…Impairment of cerebrospinal fluid (CSF) circulation is the primary mechanism of posthemorrhagic hydrocephalus [17][18][19]. For a long time, the exact pathways and functions of CSF circulation remained unclear.…”

Role of Perilipins in Oxidative Stress—Implications for Cardiovascular Disease

“…Among all the described inflammasomes, the nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasome has been the most investigated due to its implication in a wide array of inflammatory human diseases [77]. Interestingly, NLRP3 affects mitochondrial ROS production by regulating LD formation [78]. NLRP3 activation was also found to be responsible for TREM1-mediated neuroinflammation and ROS production in microglial cells [79].…”