Targeting High Mobility Group Box 1 in Subarachnoid Hemorrhage : A Systematic Review

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Muhammad , S , Chaudhry , S R , Kahlert , U D , Lehecka , M , Korja , M , Niemelä , M & Hänggi , D 2020 , ' Targeting High Mobility Group Box 1 in Subarachnoid Hemorrhage : A Systematic Review ' , International Journal of Molecular Sciences , vol. 21 , no. 8 , 2709 . https://doi.org/10.3390/ijms21082709

Title: Targeting High Mobility Group Box 1 in Subarachnoid Hemorrhage : A Systematic Review
Author: Muhammad, Sajjad; Chaudhry, Shafqat Rasul; Kahlert, Ulf Dietrich; Lehecka, Martin; Korja, Miikka; Niemelä, Mika; Hänggi, Daniel
Contributor: University of Helsinki, HUS Neurocenter
University of Helsinki, HUS Neurocenter
University of Helsinki, HUS Neurocenter
University of Helsinki, Department of Neurosciences
Date: 2020-04
Language: eng
Number of pages: 14
Belongs to series: International Journal of Molecular Sciences
ISSN: 1422-0067
URI: http://hdl.handle.net/10138/316318
Abstract: Aneurysmal subarachnoid hemorrhage (aSAH) is a complex and potentially deadly disease. Neurosurgical clipping or endovascular coiling can successfully obliterate ruptured aneurysms in almost every case. However, despite successful interventions, the clinical outcomes of aSAH patients are often poor. The reasons for poor outcomes are numerous, including cerebral vasospasm (CVS), post-hemorrhagic hydrocephalus, systemic infections and delayed cerebral ischemia. Although CVS with subsequent cerebral ischemia is one of the main contributors to brain damage after aSAH, little is known about the underlying molecular mechanisms of brain damage. This review emphasizes the importance of pharmacological interventions targeting high mobility group box 1 (HMGB1)-mediated brain damage after subarachnoid hemorrhage (SAH) and CVS. We searched Pubmed, Ovid medline and Scopus for "subarachnoid hemorrhage" in combination with "HMGB1". Based on these criteria, a total of 31 articles were retrieved. After excluding duplicates and selecting the relevant references from the retrieved articles, eight publications were selected for the review of the pharmacological interventions targeting HMGB1 in SAH. Damaged central nervous system cells release damage-associated molecular pattern molecules (DAMPs) that are important for initiating, driving and sustaining the inflammatory response following an aSAH. The discussed evidence suggested that HMGB1, an important DAMP, contributes to brain damage during early brain injury and also to the development of CVS during the late phase. Different pharmacological interventions employing natural compounds with HMGB1-antagonizing activity, antibody targeting of HMGB1 or scavenging HMGB1 by soluble receptors for advanced glycation end products (sRAGE), have been shown to dampen the inflammation mediated brain damage and protect against CVS. The experimental data suggest that HMGB1 inhibition is a promising strategy to reduce aSAH-related brain damage and CVS. Clinical studies are needed to validate these findings that may lead to the development of potential treatment options that are much needed in aSAH.
Subject: subarachnoid hemorrhage
damage-associated molecular pattern molecules (DAMPs)
alarmins
HMGB1 (High mobility group box 1)
CVS (Cerebral vasospasm)
BLOOD-BRAIN-BARRIER
DELAYED CEREBRAL-ISCHEMIA
GLYCYRRHIZIC ACID
HMGB1
INJURY
RAGE
INFLAMMATION
VASOSPASM
EXPRESSION
BIOMARKERS
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
3112 Neurosciences
3124 Neurology and psychiatry
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