Inhibition of acid-sensing receptor GPR4 attenuates neuronal ferroptosis via RhoA/YAP signaling in a rat model of subarachnoid hemorrhage.

Background And Purpose: Subarachnoid hemorrhage (SAH) is a devastating stroke, in which acidosis is one of detrimental complications. The extracellular pH reduction can activate G protein-coupled receptor 4 (GPR4) in the brain. Yet, the extent to which proton-activated GPR4 contributes to the early brain injury (EBI) post-SAH remains largely unexplored.

PEDF-34 attenuates neurological deficit and suppresses astrocyte-dependent neuroinflammation by modulating astrocyte polarization via 67LR/JNK/STAT1 signaling pathway after subarachnoid hemorrhage in rats.

Background: Reactive astrocytes participate in various pathophysiology after subarachnoid hemorrhage (SAH), including neuroinflammation, glymphatic-lymphatic system dysfunction, brain edema, BBB disruption, and cell death. Astrocytes transform into two new reactive phenotypes with changed morphology, altered gene expression, and secretion profiles, termed detrimental A1 and beneficial A2. This study investigates the effect of 67LR activation by PEDF-34, a PEDF peptide, on neuroinflammation and astrocyte polarization after the experimental SAH.

Therapeutic potential of stem cells in subarachnoid hemorrhage.

Aneurysm rupture can result in subarachnoid hemorrhage, a condition with potentially severe consequences, such as disability and death. In the acute stage, early brain injury manifests as intracranial pressure elevation, global cerebral ischemia, acute hydrocephalus, and direct blood-brain contact due to aneurysm rupture. This may subsequently cause delayed cerebral infarction, often with cerebral vasospasm, significantly affecting patient outcomes.

UDP-Glucose/P2Y14 Receptor Signaling Exacerbates Neuronal Apoptosis After Subarachnoid Hemorrhage in Rats.

Background: Subarachnoid hemorrhage (SAH) is a severe subtype of stroke with poor outcomes. Abnormal glucose metabolism often occurs after SAH, but the strict control of blood glucose levels is not always beneficial. This study aimed to investigate the contribution of uridine diphosphate glucose (UDP-G), an intermediate of glucose/glycogen metabolism, and its receptor P2Y14 (P2Y purinoceptor 14) to SAH pathology and explored the potential targeted treatments in rats.

Fractalkine Enhances Hematoma Resolution and Improves Neurological Function via CX3CR1/AMPK/PPARγ Pathway After GMH.

Background: Hematoma clearance has been a proposed therapeutic strategy for hemorrhagic stroke. This study investigated the impact of CX3CR1 (CX3C chemokine receptor 1) activation mediated by r-FKN (recombinant fractalkine) on hematoma resolution, neuroinflammation, and the underlying mechanisms involving AMPK (AMP-activated protein kinase)/PPARγ (peroxisome proliferator-activated receptor gamma) pathway after experimental germinal matrix hemorrhage (GMH).

Methods: A total of 313 postnatal day 7 Sprague Dawley rat pups were used.

Epidermal Growth Factor Receptor Mediates Neuronal Apoptosis After Subarachnoid Hemorrhage in Mice.

Background: Early brain injury including neuronal apoptosis is a main contributor to neurological deterioration after subarachnoid hemorrhage (SAH). This study was aimed to investigate whether EGFR (epidermal growth factor receptor)/NFκB (nuclear factor-kappa B) inducing kinase (NIK)/NFκB (p65 and p50) pathway is involved in the neuronal apoptosis after SAH in mice.

Methods: C57BL/6 adult male mice underwent endovascular perforation SAH modeling or sham-operation (n=286), and 86 mild SAH mice were excluded.

Anti-Apoptotic Effects of AMPA Receptor Antagonist Perampanel in Early Brain Injury After Subarachnoid Hemorrhage in Mice.

This study was aimed to investigate if acute neuronal apoptosis is induced by activation of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionate) receptors (AMPARs) and inhibited by a clinically available selective AMPAR antagonist and antiepileptic drug perampanel (PER) in subarachnoid hemorrhage (SAH), and if the mechanisms include upregulation of an inflammation-related matricellular protein periostin. Sham-operated and endovascular perforation SAH mice randomly received an administration of 3 mg/kg PER or the vehicle intraperitoneally. Post-SAH neurological impairments and increased caspase-dependent neuronal apoptosis were associated with activation of AMPAR subunits GluA1 and GluA2, and upregulation of periostin and proinflammatory cytokines interleukins-1β and -6, all of which were suppressed by PER.

Role of Estrogen-Related Receptor γ and PGC-1α/SIRT3 Pathway in Early Brain Injury After Subarachnoid Hemorrhage.

Estrogen-related receptors (ERRs) were shown to play an important role in the regulation of free radical-mediated pathology. This study aimed to investigate the neuroprotective effect of ERRγ activation against early brain injury (EBI) after subarachnoid hemorrhage (SAH) and the potential underlying mechanisms. In a rat model of SAH, the time course of ERRs and SIRT3 and the effects of ERRγ activation were investigated.

Roles of glutamate in brain injuries after subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (SAH) is a stroke type with a high rate of mortality and morbidity. Post-SAH brain injury as a determinant of poor outcome is classified into the following two types: early brain injury (EBI) and delayed cerebral ischemia (DCI). EBI consists of various acute brain pathophysiologies that occur within the first 72 hours of SAH in a clinical setting.

Nonfasting Triglyceride as an Independent Predictor of Carotid Restenosis After Carotid Endarterectomy or Carotid Artery Stenting.

Objective: Nonfasting serum triglyceride (TG) level is attracting more and more attention as an atherosclerosis-promoting factor. However, no study has investigated the relationships between nonfasting TG levels and carotid restenosis after carotid endarterectomy (CEA) or carotid artery stenting (CAS). This study was conducted to investigate if nonfasting TG levels can be used to assess a risk for carotid restenosis after CEA or CAS.

Inhibition of AMPA (α-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionate) Receptor Reduces Acute Blood-Brain Barrier Disruption After Subarachnoid Hemorrhage in Mice.

Activation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor (AMPAR) is thought to cause acute brain injury, but the role remains poorly understood in subarachnoid hemorrhage (SAH). This study was conducted to evaluate if AMPAR activation induces acute blood-brain barrier (BBB) disruption after SAH. C57BL/6 male adult mice (n = 117) underwent sham or filament perforation SAH modeling, followed by a random intraperitoneal injection of vehicle or two dosages (1 mg/kg or 3 mg/kg) of a selective noncompetitive AMPAR antagonist perampanel (PER) at 30 min post-modeling.

Higher Non-fasting Serum Triglyceride Preceding the Carotid Stenosis Progression.

The present study was conducted to investigate whether non-fasting serum triglyceride (TG) levels can be used to assess a risk for the progression of carotid artery stenosis. This was a single-center retrospective study. Consecutive 96 patients with ≥50% stenosis of at least unilateral cervical internal carotid artery and normal fasting serum low-density lipoprotein cholesterol (LDL-C) levels of ≤140 mg/dL were followed up for at least 1 year (mean, 3.

Clarithromycin Ameliorates Early Brain Injury After Subarachnoid Hemorrhage via Suppressing Periostin-Related Pathways in Mice.

Subarachnoid hemorrhage (SAH) remains a life-threatening disease, and early brain injury (EBI) is an important cause of poor outcomes. The authors have reported that periostin, a matricellular protein, is one of key factors of post-SAH EBI. Clarithromycin (CAM) is a worldwide antibiotic that can inhibit periostin expression.

Higher Plasma Osteopontin Concentrations Associated with Subsequent Development of Chronic Shunt-Dependent Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage.

A matricellular protein osteopontin (OPN) is considered to exert neuroprotective and healing effects on neurovascular injuries in an acute phase of aneurysmal subarachnoid hemorrhage (SAH). However, the relationships between OPN expression and chronic shunt-dependent hydrocephalus (SDHC) have never been investigated. In 166 SAH patients (derivation and validation cohorts, 110 and 56, respectively), plasma OPN levels were serially measured at days1-3, 4-6, 7-9, and 10-12 after aneurysmal obliteration.

Cerebrovascular pathophysiology of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (SAH) remains a serious cerebrovascular disease. Even if SAH patients survive the initial insults, delayed cerebral ischemia (DCI) may occur at 4 days or later post-SAH. DCI is characteristics of SAH, and is considered to develop by blood breakdown products and inflammatory reactions, or secondary to early brain injury, acute pathophysiological events that occur in the brain within the first 72 hours of aneurysmal SAH.

Prognostic factors varying with age in patients with aneurysmal subarachnoid hemorrhage.

With the advent of an aging society, more elderly patients with aneurysmal subarachnoid hemorrhage (aSAH) have been treated. We investigated if prognostic factors differ with age in aSAH patients. In a prospectively maintained aSAH database at multiple institutions from 2013 to 2016, 238 patients who underwent clipping or coiling for a ruptured aneurysm within 48 h of onset were divided into elderly (≥75 years; 57 patients) and non-elderly groups, or categorized into 4-age groups (<54, 55-64, 65-74, and ≥75 years).

Morphological Characteristics of Neuronal Death After Experimental Subarachnoid Hemorrhage in Mice Using Double Immunoenzymatic Technique.

Subarachnoid hemorrhage (SAH) is a devastating disease. Neuronal death is an important pathophysiology in the acute phase of SAH, but the histopathological features of dying neurons have been poorly studied. Using several staining methods including terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and microtubule-associated protein 2 (MAP-2) double immunolabeling, we investigated the morphological changes of nucleus and cytoskeleton in neurons and sought susceptible areas to neuronal death in filament perforation SAH mice under light microscope.

Machine Learning Analysis of Matricellular Proteins and Clinical Variables for Early Prediction of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.

Although delayed cerebral ischemia (DCI) is a well-known complication after subarachnoid hemorrhage (SAH), there are no reliable biomarkers to predict DCI development. Matricellular proteins (MCPs) have been reported relevant to DCI and expected to become biomarkers. As machine learning (ML) enables the classification of various input data and the result prediction, the aim of this study was to construct early prediction models of DCI development with clinical variables and MCPs using ML analyses.

Potential therapeutic molecular targets for blood-brain barrier disruption after subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage remains serious hemorrhagic stroke with high morbidities and mortalities. Aneurysm rupture causes arterial bleeding-induced mechanical brain tissue injuries and elevated intracranial pressure, followed by global cerebral ischemia. Post-subarachnoid hemorrhage ischemia, tissue injuries as well as extravasated blood components and the breakdown products activate microglia, astrocytes and Toll-like receptor 4, and disrupt blood-brain barrier associated with the induction of many inflammatory and other cascades.

Plasma Periostin and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.

Delayed cerebral ischemia (DCI) is a serious complication of aneurysmal subarachnoid hemorrhage (SAH). Matricellular protein periostin (POSTN) has been found to be upregulated and linked with early brain injury after experimental SAH. The aim of the present study was to investigate the relationship between plasma POSTN levels and various clinical factors including serum levels of C-reactive protein (CRP), an inflammatory marker, in 109 consecutive SAH patients whose POSTN levels were measured at days 1-12 after aneurysmal obliteration.

Anti-vasospastic Effects of Epidermal Growth Factor Receptor Inhibitors After Subarachnoid Hemorrhage in Mice.

Subarachnoid hemorrhage (SAH) is a devastating disease. Cerebral vasospasm is still an important cause of post-SAH poor outcomes, but its mechanisms remain unveiled. Activation of epidermal growth factor receptor (EGFR) is suggested to cause vasoconstriction in vitro, but no report has demonstrated the involvement of EGFR in vasospasm development after SAH in vivo.

Modified Citrus Pectin Prevents Blood-Brain Barrier Disruption in Mouse Subarachnoid Hemorrhage by Inhibiting Galectin-3.

Background and Purpose- Plasma levels of galectin-3-a matricellular protein-are increased after aneurysmal subarachnoid hemorrhage (SAH), but the functional significance remains undetermined. This study was conducted to evaluate whether modified citrus pectin (MCP; galectin-3 inhibitor) prevents post-SAH early brain injury, focusing on blood-brain barrier disruption. Methods- C57BL/6 male adult mice (n=251) underwent sham or filament perforation SAH modeling, followed by a random intracerebroventricular injection of vehicle or drug at 30 minutes post-modeling.