Annexin A1 attenuates neuroinflammation through FPR2/p38/COX‐2 pathway after intracerebral hemorrhage in male mice

Abstract

Spontaneous intracerebral hemorrhage (ICH) is the deadliest stroke subtype and neuroinflammation is a critical component of the pathogenesis following ICH. Annexin A1-FPR2 signaling has been shown to play a protective role in animal stroke models. This study aimed to assess whether Annexin A1 attenuated neuroinflammation and brain edema after ICH and investigate the underlying mechanisms. Male CD-1 mice were subjected to collagenase-induced ICH. Annexin A1 was administered at 0.5 hr after ICH. Brain water content measurement, short-term and long-term neurobehavioral tests, Western blot and immnunofluorescence were performed. Results showed that Annexin A1 effectively attenuated brain edema, improved short-term neurological function and ameliorated microglia activation after ICH. Annexin A1 also improved memory function at 28 days after ICH. However, these beneficial effects were abolished with the administration of FPR2 antagonist Boc-2. Furthermore, AnxA1/FPR2 signaling may confer protective effects via inhibiting p38-associated inflammatory cascade. Our study demonstrated that Annexin A1/FPR2/p38 signaling pathway played an important role in attenuating neuroinflammation after ICH and that Annexin A1 could be a potential therapeutic strategy for ICH patients.

Activation of PPAR-β/δ Attenuates Brain Injury by Suppressing Inflammation and Apoptosis in a Collagenase-Induced Intracerebral Hemorrhage Mouse Model

“…ICH-induced pathophysiological changes include neuroinflammation, excitotoxicity, and neural cell apoptosis. The inflammatory response is a significant element of the pathological process of ICH, resulting in brain injury and neurobehavioral damage [4]. The most important features of the inflammatory response are the activation of microglia, infiltration of leukocytes, and release of a large number of cytokines and chemokines [5].…”

Annexin A2 depletion exacerbates the intracerebral microhemorrhage induced by acute rickettsia and Ebola virus infections

“…A population-based retrospective cohort study revealed that 18% of patients with central nervous system (CNS) infections developed CMHs within one year after the initial infection, 47 times greater than non-CNS infection controls [34]. Infections complicating cerebrovascular accidents have been extensively investigated [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54]. However, the role of CMHs complicating infections [55][56][57][58], in particular, acute infections, has been poorly explored [34,[59][60][61].…”

Metal ion-responsive nanocarrier derived from phosphonated calix[4]arenes for delivering dauricine specifically to sites of brain injury in a mouse model of intracerebral hemorrhage

“…Toxins released from an intracerebral hematoma may contribute to brain damage after ICH [37]. Two putative neurotoxins are hemoglobin, the most abundant protein in blood, and its heme group, which are released from lysed erythrocytes after ICH [38][39][40] Hemoglobin and its heme group play an essential role in ROS production after ICH [41][42][43]. In addition, hemoglobin can be metabolized into ferrous/ferric iron and form hydroxyl radicals via the Fenton reaction [44].…”