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Role of Damage Associated Molecular Pattern Molecules (DAMPs) in Aneurysmal Subarachnoid Hemorrhage (aSAH).

ABSTRACT: Aneurysmal subarachnoid hemorrhage (aSAH) represents only a small portion of all strokes, but accounts for almost half of the deaths caused by stroke worldwide. Neurosurgical clipping and endovascular coiling can successfully obliterate the bleeding aneurysms, but ensuing complications such as cerebral vasospasm, acute and chronic hydrocephalus, seizures, cortical spreading depression, delayed ischemic neurological deficits, and delayed cerebral ischemia lead to poor clinical outcomes. The mechanisms leading to these complications are complex and poorly understood. Early brain injury resulting from transient global ischemia can release molecules that may be critical to initiate and sustain inflammatory response. Hence, the events during early brain injury can influence the occurrence of delayed brain injury. Since the damage associated molecular pattern molecules (DAMPs) might be the initiators of inflammation in the pathophysiology of aSAH, so the aim of this review is to highlight their role in the context of aSAH from diagnostic, prognostic, therapeutic, and drug therapy monitoring perspectives. DAMPs represent a diverse and a heterogenous group of molecules derived from different compartments of cells upon injury. Here, we have reviewed the most important DAMPs molecules including high mobility group box-1 (HMGB1), S100B, hemoglobin and its derivatives, extracellular matrix components, IL-1?, IL-33, and mitochondrial DNA in the context of aSAH and their role in post-aSAH complications and clinical outcome after aSAH.

SUBMITTER: Chaudhry SR

PROVIDER: S-EPMC6073937 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Role of Damage Associated Molecular Pattern Molecules (DAMPs) in Aneurysmal Subarachnoid Hemorrhage (aSAH).

Chaudhry Shafqat Rasul SR Hafez Ahmad A Rezai Jahromi Behnam B Kinfe Thomas Mehari TM Lamprecht Alf A Niemelä Mika M Muhammad Sajjad S

International journal of molecular sciences 20180713 7

Aneurysmal subarachnoid hemorrhage (aSAH) represents only a small portion of all strokes, but accounts for almost half of the deaths caused by stroke worldwide. Neurosurgical clipping and endovascular coiling can successfully obliterate the bleeding aneurysms, but ensuing complications such as cerebral vasospasm, acute and chronic hydrocephalus, seizures, cortical spreading depression, delayed ischemic neurological deficits, and delayed cerebral ischemia lead to poor clinical outcomes. The mecha ...[more]

PMID: 30011792

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Project description:ObjectiveOutcome after aneurysmal subarachnoid hemorrhage (aSAH) is highly variable and largely determined by early brain injury and delayed cerebral ischemia (DCI). Soluble urokinase plasminogen activator receptor (suPAR) represents a promising inflammatory marker which has previously been associated with outcome in traumatic brain injury and stroke patients. However, its relevance in the context of inflammatory changes after aSAH is unclear. Here, we aimed to characterize the role of circulating suPAR in both serum and cerebrospinal fluid (CSF) as a novel biomarker for aSAH patients.MethodsA total of 36 aSAH patients, 10 control patients with unruptured abdominal aneurysm and 32 healthy volunteers were included for analysis. suPAR was analyzed on the day of admission in all patients. In aSAH patients, suPAR was also determined on the day of DCI and the respective time frame in asymptomatic patients. One- and two-sample t-tests were used for simple difference comparisons within and between groups. Regression analysis was used to assess the influence of suPAR levels on outcome in terms of modified Rankin score.ResultsSignificantly elevated suPAR serum levels (suPAR-SL) on admission were found for aSAH patients compared to healthy controls, but not compared to vascular control patients. Disease severity as documented according to Hunt and Hess grade and modified Fisher grade was associated with higher suPAR CSF levels (suPAR-CSFL). In aSAH patients, suPAR-SL increased daily by 4%, while suPAR-CSFL showed a significantly faster daily increase by an average of 22.5% per day. Each increase of the suPAR-SL by 1 ng/ml more than tripled the odds of developing DCI (OR = 3.06). While admission suPAR-CSFL was not predictive of DCI, we observed a significant correlation with modified Rankin's degree of disability at discharge.ConclusionElevated suPAR serum level on admission as a biomarker for early inflammation after aSAH is associated with an increased risk of DCI. Elevated suPAR-CSFL levels correlate with a higher degree of disability at discharge. These distinct relations and the observation of a continuous increase over time affirm the role of inflammation in aSAH and require further study.

Project description:ObjectiveSubarachnoid haemorrhage (SAH), caused by the rupture of intracranial aneurysms, is a devastating event with high rates of morbidity and mortality. Aneurysmal subarachnoid haemorrhage (aSAH) plays a critical role in the potential loss of life as its sufferers are usually of a young age. We aimed to investigate the incidence of aSAH along with the patients' characteristics over five consecutive years in Fars, a large province located in Southern Iran.MethodsIn this prospective study, anonymous data of all patients diagnosed with aSAH in Fars province were collected after patient admission and surgery. Data from the last national census in 2011 were used to calculate the incidence. The data were analysed using SPSS software version 18 using independent sample t test, chi square test and ANOVA. The significance level was set at 0.05.ResultsThe number of aSAH cases identified in Fars, Iran, each year varied between 78 (2011) and 98 (2015) for a total of 421 aSAH cases within the 5-year study period. The annual aSAH incidence estimates showed no differences and were 1.65 [95% confidence interval (CI): 1.58-1.72], 1.70 (95%CI: 1.68-1.72), 1.71 (95%CI: 1.63-1.78), 1.82 (95%CI: 1.74-1.9), and 2.05 (95%CI: 1.97-2.13) per 100,000 persons, respectively, for the five consecutive years from 21 March 2011 to 20 March 2016. Hypertension was the most common risk factor, and was found in 198 (48%) aSAH patients. Ninety-four (22.5%) patients had moderate hydrocephalus on admission. Middle cerebral artery and anterior communicating artery were the most common sites of aneurysms. On admission, 351 (83%) patients had a Glasgow Coma Scale score >7, 197 (47%) presented with Hunt and Hess score of 1, and 365 (87%) had a Fisher score of ≤3. Multiple aneurysms were found in 59 (14%) of the 421 cases and the most common risk factors in multiple aneurysms were hypertension in 30 (51%) and smoking in 26 (44%) cases. Survival data were available only on patients diagnosed in year 2015, and the six-month survival rate was 89.8%.ConclusionsThis study revealed that although the incidence of aSAH remained stable, the survival of aSAH patients who reached the hospital alive and were operated on, improved in Shiraz (the six-month survival rate was 89.8% in year 2015). The incidence and survival study on aSAH in other geographic areas of Iran as a multi-centre study is recommended. There is a need to inform primary healthcare workers regarding the possibility of aSAH in a patient with signs of the sentinel headache.

Dataset Information

Role of Damage Associated Molecular Pattern Molecules (DAMPs) in Aneurysmal Subarachnoid Hemorrhage (aSAH).

Publications

Role of Damage Associated Molecular Pattern Molecules (DAMPs) in Aneurysmal Subarachnoid Hemorrhage (aSAH).

Similar Datasets

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