Involvement of Periostin in Acute Neuronal Apoptosis Induced by Subarachnoid Hemorrhage in Mice and its Suppression by Clarithromycin.

Background: Periostin is an inflammation-related matricellular protein that has been reported to increase in the acute phase after subarachnoid hemorrhage (SAH) in clinical settings. However, its relationship with neuronal apoptosis, a characteristic of early brain injury, remains unknown. The purpose of this study was to investigate the involvement of periostin in SAH-induced acute neuronal apoptosis and to determine whether clarithromycin (CAM), a macrolide antibiotic known to suppress periostin expression, prevents acute neuronal apoptosis after SAH in mice.

Tenascin-C as a Target for Intervention in Delayed Cerebral Ischemia After Subarachnoid Hemorrhage.

The outcomes of aneurysmal subarachnoid hemorrhage (SAH) remain poor, and delayed cerebral ischemia (DCI) is the most important treatable determinant for a poor outcome. Clinical and experimental findings have shown that more-severe SAH induces more tenascin-C (TNC) in brain parenchyma, cerebral artery walls, cerebrospinal fluid, and peripheral blood, which is involved in the development of DCI. TNC belongs to inducible, nonstructural, and multifunctional matricellular proteins.

The effect of Fibulin-5 on early brain injury after subarachnoid hemorrhage in mice.

Early brain injury (EBI) is an important cause that determines outcomes after aneurysmal subarachnoid hemorrhage (SAH). Our recent clinical study reported that a high concentration of plasma fibulin-5 (FBLN5), one of matricellular proteins, was associated with poor outcomes after SAH. The aim of this study was to investigate whether and how FBLN5 was associated with EBI during an acute phase of SAH in mice.

Spinal Drainage and Combined Pharmacotherapy as Potential Strategies to Improve Outcomes for Patients with Poor-Grade Subarachnoid Hemorrhage Treated with Clipping or Coiling but Not Receiving Nimodipine.

: The outcome for aneurysmal subarachnoid hemorrhage (SAH) remains poor, particularly for patients presenting with World Federation of Neurological Surgeons (WFNS) grades IV-V. This study was designed to identify independent prognostic factors in this group of patients with poor-grade SAH. : We prospectively analyzed 357 SAH patients with admission WFNS grades IV-V enrolled in nine primary stroke centers in Mie prefecture, Japan, from 2013 to 2022.

Increased Plasma Levels of Thrombin-Cleaved Osteopontin in Patients with Delayed Cerebral Infarction After Aneurysmal Subarachnoid Hemorrhage.

Osteopontin (OPN), a matricellular protein, is produced as a full-length OPN (FL-OPN) and cleaved by thrombin, thus generating the N-terminal half of OPN (OPN N-half) with new functions. Although plasma FL-OPN levels have been associated with neurovascular events after aneurysmal subarachnoid hemorrhage (SAH), plasma OPN N-half levels have never been investigated. In this study, prospective clinical data and plasma samples were collected from 108 consecutive SAH patients with ruptured aneurysms undergoing acute treatment via surgery, and FL-OPN and OPN N-half levels were measured in plasma with a particular focus on delayed cerebral infarction (DCIn), which has the greatest impact on outcomes.

Independent elevation of plasma fibulin-5 proceeding chronic hydrocephalus development after aneurysmal subarachnoid hemorrhage.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) causes chronic hydrocephalus (CH) due to disturbance in the reabsorption of cerebrospinal fluid following subarachnoidal fibrosis via inflammatory reactions or blood clotting products. Fibulin-5 (FBLN5) is one of matricellular proteins associated with fibrosis processes.

Objective: The aim of this study was to assess whether FBLN5 elevation is related to CH after aSAH.

Treatment factors to suppress delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage based on VASOGRADE: multicenter cohort study.

Delayed cerebral ischemia (DCI) is one of the most important outcome determinants for aneurysmal subarachnoid hemorrhage (aSAH). VASOGRADE, which combines World Federation of Neurological Surgeons grade and modified Fisher grade, is a useful scale for predicting DCI after aSAH. However, no studies have investigated whether VASOGRADE influences the treatment options.

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.

Inflammatory Skin Disease Causes Anxiety Symptoms Leading to an Irreversible Course.

Intense itching significantly reduces the quality of life, and atopic dermatitis is associated with psychiatric conditions, such as anxiety and depression. Psoriasis, another inflammatory skin disease, is often complicated by psychiatric symptoms, including depression; however, the pathogenesis of these mediating factors is poorly understood. This study used a spontaneous dermatitis mouse model (KCASP1Tg) and evaluated the psychiatric symptoms.

Plasma SPARC Elevation in Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.

Matricellular proteins have been implicated in pathologies after subarachnoid hemorrhage (SAH). To find a new therapeutic molecular target, the present study aimed to clarify the relationships between serially measured plasma levels of a matricellular protein, secreted protein acidic and rich in cysteine (SPARC), and delayed cerebral ischemia (DCI) in 117 consecutive aneurysmal SAH patients with admission World Federation of Neurological Surgeons (WFNS) grades I-III. DCI developed in 25 patients with higher incidences of past history of hypertension and dyslipidemia, preoperative WFNS grade III, modified Fisher grade 4, spinal drainage, and angiographic vasospasm.

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.

Plasma Fibulin-5 Levels as an Independent Predictor of a Poor Outcome after an Aneurysmal Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage (SAH) is a poor-outcome disease with a delayed neurological exacerbation. Fibulin-5 (FBLN5) is one of matricellular proteins, some of which have been involved in SAH pathologies. However, no study has investigated FBLN5's roles in SAH.

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.

Neuroelectric Mechanisms of Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage.

Delayed cerebral ischemia (DCI) remains a challenging but very important condition, because DCI is preventable and treatable for improving functional outcomes after aneurysmal subarachnoid hemorrhage (SAH). The pathologies underlying DCI are multifactorial. Classical approaches to DCI focus exclusively on preventing and treating the reduction of blood flow supply.

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.

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).