scholarly journals Complement C5 Contributes to Brain Injury After Subarachnoid Hemorrhage

2019 ◽  
Vol 11 (4) ◽  
pp. 678-688 ◽  
Author(s):  
Bart J. van Dijk ◽  
Joost C.M. Meijers ◽  
Anne T. Kloek ◽  
Veronique L. Knaup ◽  
Gabriel J.E. Rinkel ◽  
...  
Keyword(s):  
Cell Death ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Mouse Model ◽  
Complement Activation ◽  
Plasma Levels ◽  
Microglia Activation ◽  
C5a Receptor ◽  
Specific Antibodies ◽  
Common Genetic Variants

AbstractPrevious studies showed that complement activation is associated with poor functional outcome after aneurysmal subarachnoid hemorrhage (SAH). We investigated whether complement activation is underlying brain injury after aneurysmal SAH (n = 7) and if it is an appropriate treatment target. We investigated complement expression in brain tissue of aneurysmal SAH patients (n = 930) and studied the role of common genetic variants in C3 and C5 genes in outcome. We analyzed plasma levels (n = 229) to identify the functionality of a single nucleotide polymorphism (SNP) associated with outcome. The time course of C5a levels was measured in plasma (n = 31) and CSF (n = 10). In an SAH mouse model, we studied the extent of microglia activation and cell death in wild-type mice, mice lacking the C5a receptor, and in mice treated with C5-specific antibodies (n = 15 per group). Brain sections from aneurysmal SAH patients showed increased presence of complement components C1q and C3/C3b/iC3B compared to controls. The complement component 5 (C5) SNP correlated with C5a plasma levels and poor disease outcome. Serial measurements in CSF revealed that C5a was > 1400-fold increased 1 day after aneurysmal SAH and then gradually decreased. C5a in plasma was 2-fold increased at days 3–10 after aneurysmal SAH. In the SAH mouse model, we observed a ≈ 40% reduction in both microglia activation and cell death in mice lacking the C5a receptor, and in mice treated with C5-specific antibodies. These data show that C5 contributes to brain injury after experimental SAH, and support further study of C5-specific antibodies as novel treatment option to reduce brain injury and improve prognosis after aneurysmal SAH.

An apoE-derived mimic peptide, COG1410, alleviates early brain injury via reducing apoptosis and neuroinflammation in a mouse model of subarachnoid hemorrhage

2016 ◽  
Vol 627 ◽  
pp. 92-99 ◽  
Author(s):  
Yue Wu ◽  
Jinwei Pang ◽  
Jianhua Peng ◽  
Fang Cao ◽  
Michael P. Vitek ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Mouse Model ◽  
Early Brain Injury ◽  
Mimic Peptide

scholarly journals Therapeutic effect of and mechanisms underlying the effect of miR-195-5p on subarachnoid hemorrhage-induced vasospasm and brain injury in rats

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11395
Author(s):  
Tai-Hsin Tsai ◽  
Chih-Hui Chang ◽  
Szu-Huai Lin ◽  
Yu-Feng Su ◽  
Yi-Cheng Tsai ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Nitric Oxide Synthase ◽  
Dentate Gyrus ◽  
Basilar Artery ◽  
Early Brain Injury ◽  
Cell Death Assay ◽  
Oxide Synthase

Objectives There is much evidence suggesting that inflammation contributes majorly to subarachnoid hemorrhage (SAH)-induced cerebral vasospasm and brain injury. miRNAs have been found to modulate inflammation in several neurological disorders. This study investigated the effect of miR-195-5p on SAH-induced vasospasm and early brain injury in experimental rats. Methods Ninety-six Sprague-Dawley male rats were randomly and evenly divided into a control group (no SAH, sham surgery), a SAH only group, a SAH + NC-mimic group, and a SAH + miR-195-5p group. SAH was induced using a single injection of blood into the cisterna magna. Suspensions containing NC-mimic and miR-195-5p were intravenously injected into rat tail 30 mins after SAH was induced. We determined degree of vasospasm by averaging areas of cross-sections the basilar artery 24h after SAH. We measured basilar artery endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κ B), phosphorylated NF-κ B (p-NF-κ B), inhibitor of NF-κ B (Iκ Bα) and phosphorylated-Iκ Bα (p-Iκ Bα). Cell death assay was used to quantify the DNA fragmentation, an indicator of apoptotic cell death, in the cortex, hippocampus, and dentate gyrus. Tumor necrosis factor alpha (TNF-α) levels were measured using sample protein obtained from the cerebral cortex, hippocampus and dentate gyrus. Results Prior to fixation by perfusion, there were no significant physiological differences among the control and treatment groups. SAH successfully induced vasospasm and early brain injury. MiR-195-5p attenuated vasospasam-induced changes in morphology, reversed SAH-induced elevation of iNOS, p-NF-κ B, NF-κ B, and p-Iκ Bα and reversed SAH-induced suppression of eNOS in the basilar artery. Cell death assay revealed that MiR-195-5p significantly decreased SAH-induced DNA fragmentation (apoptosis) and restored TNF-α level in the dentate gyrus. Conclusion In conclusion, MiRNA-195-5p attenuated SAH-induced vasospasm by up-regulating eNOS, down-regulating iNOS and inhibiting the NF-κ B signaling pathway. It also protected neurons by decreasing SAH-induced apoptosis-related cytokine TNF-α expression in the dentate gyrus. Further study is needed to elucidate the detail mechanism underlying miR-195-5p effect on SAH-induced vasospasm and cerebral injury. We believe that MiR-195-5p can potentially be used to manage SAH-induced cerebral vasospasm and brain injury.

Early dysglycemia and mortality in traumatic brain injury and subarachnoid hemorrhage

2019 ◽  
Vol 85 (8) ◽  
Author(s):  
Simone Pappacena ◽  
Michael Bailey ◽  
Luca Cabrini ◽  
Giovanni Landoni ◽  
Andrew Udy ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury

Evidence for a conditioning effect of inhalational anesthetics on angiographic vasospasm after aneurysmal subarachnoid hemorrhage

2020 ◽  
Vol 133 (1) ◽  
pp. 152-158 ◽  
Author(s):  
Umeshkumar Athiraman ◽  
Diane Aum ◽  
Ananth K. Vellimana ◽  
Joshua W. Osbun ◽  
Rajat Dhar ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Multivariate Logistic Regression Analysis ◽  
Secondary Brain Injury ◽  
Large Artery ◽  
Inhalational Anesthetics ◽  
Angiographic Vasospasm ◽  
Inhalational Anesthetic

OBJECTIVEDelayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) is characterized by large-artery vasospasm, distal autoregulatory dysfunction, cortical spreading depression, and microvessel thrombi. Large-artery vasospasm has been identified as an independent predictor of poor outcome in numerous studies. Recently, several animal studies have identified a strong protective role for inhalational anesthetics against secondary brain injury after SAH including DCI—a phenomenon referred to as anesthetic conditioning. The aim of the present study was to assess the potential role of inhalational anesthetics against cerebral vasospasm and DCI in patients suffering from an SAH.METHODSAfter IRB approval, data were collected retrospectively for all SAH patients admitted to the authors’ hospital between January 1, 2010, and December 31, 2013, who received general anesthesia with either inhalational anesthetics only (sevoflurane or desflurane) or combined inhalational (sevoflurane or desflurane) and intravenous (propofol) anesthetics during aneurysm treatment. The primary outcomes were development of angiographic vasospasm and development of DCI during hospitalization. Univariate and logistic regression analyses were performed to identify independent predictors of these endpoints.RESULTSThe cohort included 157 SAH patients whose mean age was 56 ± 14 (± SD). An inhalational anesthetic–only technique was employed in 119 patients (76%), while a combination of inhalational and intravenous anesthetics was employed in 34 patients (22%). As expected, patients in the inhalational anesthetic–only group were exposed to significantly more inhalational agent than patients in the combination anesthetic group (p < 0.05). Multivariate logistic regression analysis identified inhalational anesthetic–only technique (OR 0.35, 95% CI 0.14–0.89), Hunt and Hess grade (OR 1.51, 95% CI 1.03–2.22), and diabetes (OR 0.19, 95% CI 0.06–0.55) as significant predictors of angiographic vasospasm. In contradistinction, the inhalational anesthetic–only technique had no significant impact on the incidence of DCI or functional outcome at discharge, though greater exposure to desflurane (as measured by end-tidal concentration) was associated with a lower incidence of DCI.CONCLUSIONSThese data represent the first evidence in humans that inhalational anesthetics may exert a conditioning protective effect against angiographic vasospasm in SAH patients. Future studies will be needed to determine whether optimized inhalational anesthetic paradigms produce definitive protection against angiographic vasospasm; whether they protect against other events leading to secondary brain injury after SAH, including microvascular thrombi, autoregulatory dysfunction, blood-brain barrier breakdown, neuroinflammation, and neuronal cell death; and, if so, whether this protection ultimately improves patient outcome.

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