scholarly journals Secondary White Matter Injury and Therapeutic Targets After Subarachnoid Hemorrhage

2021 ◽  
Vol 12 ◽  
Author(s):  
Xufang Ru ◽  
Ling Gao ◽  
Jiru Zhou ◽  
Qiang Li ◽  
Shilun Zuo ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
White Matter ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Mechanical Damage ◽  
White Matter Injury ◽  
Neurological Deficits ◽  
Intracerebral Pressure ◽  
Heavy Burden

Aneurysmal subarachnoid hemorrhage (SAH) is one of the special stroke subtypes with high mortality and mobility. Although the mortality of SAH has decreased by 50% over the past two decades due to advances in neurosurgery and management of neurocritical care, more than 70% of survivors suffer from varying degrees of neurological deficits and cognitive impairments, leaving a heavy burden on individuals, families, and the society. Recent studies have shown that white matter is vulnerable to SAH, and white matter injuries may be one of the causes of long-term neurological deficits caused by SAH. Attention has recently focused on the pivotal role of white matter injury in the pathophysiological processes after SAH, mainly related to mechanical damage caused by increased intracerebral pressure and the metabolic damage induced by blood degradation and hypoxia. In the present review, we sought to summarize the pathophysiology processes and mechanisms of white matter injury after SAH, with a view to providing new strategies for the prevention and treatment of long-term cognitive dysfunction after SAH.

Gray-to-white matter ratio predicts long-term recovery potential of patients with aneurysmal subarachnoid hemorrhage

2018 ◽  
Vol 43 (1) ◽  
pp. 195-202 ◽  
Author(s):  
Achmet Ali ◽  
Burcu Bitir ◽  
Taner Abdullah ◽  
Pulat Akin Sabanci ◽  
Yavuz Aras ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
White Matter ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Recovery Potential

Preventing Microthrombi Formation Improves Function After Subarachnoid Hemorrhage in Mice

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Hussein Zeineddine ◽  
Spiros L Blackburn ◽  
Remya Veettil ◽  
Kanako Matsumura ◽  
Devin McBride
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Behavioral Assessment ◽  
Delayed Cerebral Ischemia ◽  
The United States ◽  
Neurological Deficits ◽  
Major Contributor ◽  
Platelet Activity ◽  
Functional Deficits

Abstract INTRODUCTION Aneurysmal subarachnoid hemorrhage (aSAH) is a debilitating disease affecting around 30 000 people per year in the United States, with a mortality estimated as high as 67%. Morbidity resulting from SAH is also extensive and includes delayed cerebral ischemia (DCI). However, the mechanism by which delayed neurological deficits develop is still poorly understood. To date, the importance of microthrombosis in SAH has been underappreciated, with few studies reporting on its occurrence and no studies probing the mechanism of microthrombi formation. We hypothesize that platelet activity results in microthrombi formation and contributes to delayed neurological deficits. We aim to address the knowledge gap in regard to the role of platelet activity and microthrombosis in DCI. METHODS For all experiments, adult male mice 4 mo old were utilized. SAH was induced using the endovascular perforation model. Behavioral assessment was performed on days 1, 3, 5, and 7 post-SAH. Animals were euthanized at 2 and 7 d post-SAH. To investigate the role of platelets in microthrombi formation after SAH, we used prototypic inhibitors of platelet activation (PAF, P2Y1,12, TP?/??R, PAR-1, −4) and platelet aggregation (GP aIIb/IIIa). RESULTS Mice with SAH had a higher microthrombi count compared to shams. Treatment with platelet inhibitors significantly reduced the number of microthrombi compared to placebo and provided protection against functional deficits. CONCLUSION SAH induces microthrombi formation, which may be a major contributor to delayed neurological deficits. Inhibition of platelet function reduces the number of microthrombi formed and confers protection against delayed functional deficits in mice models of SAH.

scholarly journals MST1 Suppression Reduces Early Brain Injury by Inhibiting the NF-κB/MMP-9 Pathway after Subarachnoid Hemorrhage in Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Jie Qu ◽  
Hengli Zhao ◽  
Qiang Li ◽  
Pengyu Pan ◽  
Kang Ma ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
White Matter ◽  
Early Brain Injury ◽  
White Matter Injury ◽  
Neurological Deficits ◽  
Tunel Staining ◽  
Blue Dye ◽  
Junction Protein ◽  
Cord Injury

Background. Mammalian sterile 20-like kinase 1 (MST1), the key component of the Hippo-YAP pathway, exhibits an important role in the pathophysiological process of various neurological disorders, including ischemic stroke and spinal cord injury. However, during subarachnoid hemorrhage, the involvement of MST1 in the pathophysiology of early brain injury remains unknown. Methods. We employed intravascular filament perforation to establish the subarachnoid hemorrhage (SAH) mouse model. The MST1 inhibitor XMU-MP-1 was intraperitoneally injected at 1 h after SAH, followed by daily injections. MST1 in vivo knockdown was performed 3 weeks prior to SAH via intracerebroventricular injection of adeno-associated virus (AAV) packaged with MST1 shRNA. The SAH grade, behavioral deficits, TUNEL staining, Evans blue dye extravasation and fluorescence, brain water content, protein and cytokine expressions by Western blotting, immunofluorescence, and proteome cytokine array were evaluated. Results. Following SAH, the phosphorylation level of MST1 was upregulated at 12 h, with a peak at 72 h after SAH. It was colocalized with the microglial marker Iba1. Both XMU-MP-1 and MST1 shRNA alleviated the neurological deficits, blood-brain barrier (BBB) disruption, brain edema, neuroinflammation, and white matter injury, which were induced by SAH in association with nuclear factor- (NF-) κB p65 and matrix metallopeptidase-9 (MMP-9) activation and downregulated endothelial junction protein expression. Conclusions. The current findings indicate that MST1 participates in SAH-induced BBB disruption and white matter fiber damage via the downstream NF-κB-MMP-9 signaling pathway. Therefore, MST1 antagonists may serve as a novel therapeutic target to prevent early brain injury in SAH patients.

scholarly journals Endothelin-1 and Endothelin Receptor Gene Variants and Their Association With Negative Outcomes Following Aneurysmal Subarachnoid Hemorrhage

2012 ◽  
Vol 15 (4) ◽  
pp. 390-397 ◽  
Author(s):  
Matthew Gallek ◽  
Sheila Alexander ◽  
Elizabeth Crago ◽  
Paula Sherwood ◽  
Michael Horowitz ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Receptor Gene ◽  
Delayed Cerebral Ischemia ◽  
The United States ◽  
Endothelin 1 ◽  
Potent Vasoconstrictor ◽  
Poor Outcomes

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating disease that affects approximately 30,000 people a year in the United States. Delayed cerebral ischemia (DCI) and cerebral vasospasm (CV) are common complications after aSAH. In addition, aSAH patients have a high risk of poor long-term outcomes. Endothelin-1 (ET-1), a potent vasoconstrictor, or its two types of receptors, ET receptor A (ETA) and ET receptor B (ETB), may play a role in the pathogenesis of DCI and CV. Genetic variations within the ET-1, ETA, or ETBgenes may also account for variance observed in the outcomes of aSAH patients. The purpose of this study was to describe the distribution of the Lys198Asn polymorphism, a known functional SNP in the ET-1 gene, and tagging SNPs of the ET-1, ETA, and ETBgenes in individuals recovering from aSAH. This study also investigated the relationships among the ET polymorphisms, DCI, and global functional outcomes measured at 3 and 6 months after aSAH. Participants included individuals aged 18–75 years with a diagnosis of aSAH. There was a trend found between the variant allele of an ET-1 SNP (rs6912834) and angiographic vasospasm. There were also associations found between two ETBSNPs (rs9574124 and rs3027111) and poor outcomes as measured by the Glasgow Outcome scale at 3 months. These findings support the role of ET-1 and ETBin recovery following aSAH.

scholarly journals Application of a free radical scavenger edaravone in patients with subarachnoid hemorrhage (review)

2021 ◽  
Vol 17 (7) ◽  
pp. 10-14
Author(s):  
O.A. Halushko ◽  
T.S. Zahranychnyi
Keyword(s):  
Free Radical ◽  
Subarachnoid Hemorrhage ◽  
Hemorrhagic Transformation ◽  
Free Radical Scavenger ◽  
Neurological Deficits ◽  
Radical Scavenger ◽  
Long Term Effects ◽  
Main Effects

Background. The free radical scavenger edaravon helps to reduce the area of ischemic injury and improve the long-term effects of stroke and is therefore widely used in the treatment of ischemic stroke. However, the role of edaravone in the treatment of patients with subarachnoid hemorrhage has not yet been clarified. The purpose was to investigate the feasibility and effectiveness of the use of the free radical scavenger xavron (edaravon) in the treatment of patients with subarachnoid hemorrhage. Materials and methods. A search was conducted for studies and systematic reviews for the keywords: “acute stroke”; “subarachnoid hemorrhage”, “hemorrhagic transformation”, “edaravon” in the Google Scholar database published between 2003 and 2021. Results. The use of edaravone in patients with subarachnoid hemorrhage was accompanied by the activation of anti-inflammatory and reduction of pro-inflammatory peptides, activation of anti-apoptotic mechanisms, reduction of lipid peroxidation, oxidative trauma, the permeability of the brain swelling. Conclusions. The main effects of edaravon (xavron) have been found to reduce neurological deficits, accelerate the recovery of neurological disorders, and improve functional outcomes. Thus, the introduction of edaravone in patients with subarachnoid hemorrhage has been proven to be reliably effective and safe.

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