Abstract 192: Mechano-growth Factor (MGF) and Cerebral Vasospasm (CV) Post Aneurysmal Subarachnoid Hemorrhage (aSAH)

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Magdalena M Przybycien-Szymanska ◽  
Todd M Rackohn ◽  
Yuchen Yang ◽  
William W Ashley
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Growth Factor ◽  
Cerebral Vasospasm ◽  
Molecular Mechanisms ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Ischemic Injury ◽  
Brain Regions ◽  
Heme Oxygenase 1 ◽  
Mechano Growth Factor ◽  
The Brain

Cerebral vasospasm (CV) and related ischemic injury is a major contributor to death and disability after aneurysmal subarachnoid hemorrhage (aSAH). Our overall goal is to understand molecular mechanisms of action of endogenous mechano-growth factor (MGF), a splice variant of insulin-like growth factor 1 (IGF-1), in the brain. MGF was found to be neuroprotective after stroke in a gerbil model of ischemic injury and may serve as a potential therapeutic target to prevent CV-induced brain damage. In our studies, we characterized hypoxia induced changes in MGF expression in different brain regions, commonly affected by CV, at different time points (from 2 hours to 7 days) post 4h hypoxia treatments (6, 8,10 or 12% oxygen). The brain regions analyzed were motor cortex, hippocampus, striatum and hypothalamus. In addition, we characterized changes in MGF expression in microparticle (MP) fractions isolated from cerebrospinal fluid (CSF) extracted from CV patients. Microparticle fractions were isolated from CSF samples using serial ultracentrifugation. We used real time RT-PCR, western blots, and enzyme immunosorbent assay to quantify changes in gene expression and protein levels. In the animal model, our results showed that there were time, dose and brain region specific changes in MGF expression that correlated with changes in the expression of heme oxygenase 1 (HO-1) and biliverdin reductase A, which are molecules involved in neuroprotection, and caspases, apoptotic markers. These results suggest that changes in endogenous MGF due to hypoxia may activate neuroprotective pathways in the brain. In CSF MPs isolated from CV patients, we observed an increase in MGF expression that correlated with the CV onset window and with an increase in HO-1, suggesting that similar pathways are activated post-CV in humans and post-hypoxia in animals. These data indicate that endogenous MGF may play a role in CV onset and may be a neuroprotective target in CV papteins. However, further studies are required to elucidate the molecular mechanisms of MGF and its exact role in CV development and patient outcome.

Stereotactic Catheter Ventriculocisternostomy for Clearance of Subarachnoid Hemorrhage in Patients with Coiled Aneurysms

2017 ◽  
Vol 14 (3) ◽  
pp. 231-235 ◽  
Author(s):  
Roland Roelz ◽  
Christian Scheiwe ◽  
Horst Urbach ◽  
Volker A Coenen ◽  
Peter Reinacher
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Blood Clearance ◽  
Fisher Grade ◽  
Rapid Clearance ◽  
Promising Treatment ◽  
Grade 3 ◽  
Subarachnoid Blood ◽  
The Brain

Abstract BACKGROUND Cerebral vasospasm leading to delayed cerebral infarction (DCI) is a central source of poor outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). Current treatments of cerebral vasospasm are insufficient. Cisternal blood clearance is a promising treatment option. However, a generally applicable, safe, and effective method to access the cisterns of the brain is lacking. OBJECTIVE To report on stereotactic catheter ventriculocisternostomy (STX-VCS) as a method to access the cisterns of the brain for clearance of subarachnoid hemorrhage in patients with aSAH and coiled aneurysms. METHODS In 9 aSAH patients at high risk for DCI (Hunt and Hess grade ≥3, modified Fisher grade ≥3), access to the basal cisterns of the brain was created by STX-VCS. Fibrinolytic and/or spasmolytic lavage therapy was administered. RESULTS STX-VCS was feasible and safe in all patients. Subarachnoid blood was rapidly cleared by irrigation with urokinase. Vasospasm occurred in 2 patients and was interrupted by irrigation with nimodipine. There was 1 fatality due to pneumogenic sepsis. Minor DCI occurred in 1 patient. Eight survived without DCI and are independent (modified Rankin score [mRS] ≤ 3) at 6 mo after aSAH. CONCLUSION STX-VCS allows for rapid clearance of subarachnoid hemorrhage in patients with coiled aneurysms.

scholarly journals Neuroimmune predictors of outcome after aneurysmal subarachnoid hemorrhage

2020 ◽  
Vol 101 (5) ◽  
pp. 754-759
Author(s):  
S V Ermakov ◽  
S M Karpov ◽  
V A Вaturin ◽  
O S Belokon ◽  
R A Mozheiko
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Nmda Receptors ◽  
Cerebral Vasospasm ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
S100 Protein ◽  
Delayed Cerebral Ischemia ◽  
Severity Of Illness ◽  
Neurospecific Proteins ◽  
The Brain ◽  
Autoantibody Level

Aim. To determine the possibility of predicting the course and outcomes of aneurysmal subarachnoid hemorrhage (aSAH) by using the detection of autoantibody level to neurospecific proteins. Methods. The autoantibody level to neurospecific proteins was detected in 65 people: 30 healthy volunteers and 35 with a confirmed diagnosis of aneurysmal subarachnoid hemorrhage. Autoantibodies to myelin basic protein (MBP), peripheral myelin, dopamine receptors, myosin, N-methyl-D-aspartate (NMDA) receptors and S100 protein detected by using an enzyme immunoassay. The severity of illness in dynamics was defined in all patients by using the following scales: Rivermead mobility index, HuntHess, Graeb and others. Statistical analysis was performed using Statistica 10.0, with the consistent use of descriptive statistics methods, the MannWhitney, KruskalWallis and Pearson tests, Spearman coefficient. Results. At the first stage, neurospecific proteins characterized by a large increase in autoantibody titers were identified. Further, based on the data obtained, a statistically significant correlation between autoantibody titers to S100 protein (360.4340.35 g/ml, p 0.05), MBP (145.9112.43 g/ml, p 0.05), NMDA receptors (66.176.42 g/ml, p 0.05) and aSAH outcome was established. Conclusion. The study revealed an increase in autoantibody level to neurospecific proteins in the blood plasma of patients, depending on the severity of subarachnoid hemorrhage and the development of delayed cerebral ischemia due to cerebral vasospasm; high antibodies titers to S100 protein in subarachnoid hemorrhage are associated with cerebral vasospasm and the development of secondary (delayed) ischemic changes in the brain.

Effect of Cilostazol on Cerebral Vasospasm and Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage: A Randomized, Double-Blind, Placebo-Controlled Trial

2016 ◽  
Vol 42 (1-2) ◽  
pp. 97-105 ◽  
Author(s):  
Naoya Matsuda ◽  
Masato Naraoka ◽  
Hiroki Ohkuma ◽  
Norihito Shimamura ◽  
Katsuhiro Ito ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Infarction ◽  
Cerebral Vasospasm ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Control Group ◽  
Independent Factor ◽  
Double Blind ◽  
End Points ◽  
Double Blind Placebo ◽  
Poor Outcome

Background: Several clinical studies have indicated the efficacy of cilostazol, a selective inhibitor of phosphodiesterase 3, in preventing cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). They were not double-blinded trial resulting in disunited results on assessment of end points among the studies. The randomized, double-blind, placebo-controlled study was performed to assess the effectiveness of cilostazol on cerebral vasospasm. Methods: Patients with aneurysmal SAH admitted within 24 h after the ictus who met the following criteria were enrolled in this study: SAH on CT scan was diffuse thick, diffuse thin, or local thick, Hunt and Hess score was less than 4, administration of cilostazol or placebo could be started within 48 h of SAH. Patients were randomly allocated to placebo or cilostazol after repair of a ruptured saccular aneurysm by aneurysmal neck clipping or endovascular coiling, and the administration of cilostazol or placebo was continued up to 14 days after initiation of treatment. The primary end point was the occurrence of symptomatic vasospasm (sVS), and secondary end points were angiographic vasospasm (aVS) evaluated on digital subtraction angiography, vasospasm-related new cerebral infarction evaluated on CT scan or MRI, and clinical outcome at 3 months of SAH as assessed by Glasgow Outcome Scale, in which poor outcome was defined as severe disability, vegetative state, and death. All end points were evaluated with blinded assessment. Results: One hundred forty eight patients were randomly allocated to the cilostazol group (n = 74) or the control group (n = 74). The occurrence of sVS was significantly lower in the cilostazol group than in the control group (10.8 vs. 24.3%, p = 0.031), and multiple logistic analysis showed that cilostazol use was an independent factor reducing sVS (OR 0.293, 95% CI 0.099-0.568, p = 0.027). The incidence of aVS and vasospasm-related cerebral infarction were not significantly different between the groups. Poor outcome was significantly lower in the cilostazol group than in the control group (5.4 vs. 17.6%, p = 0.011), and multiple logistic analyses demonstrated that cilostazol use was an independent factor that reduced the incidence of poor outcome (OR 0.221, 95% CI 0.054-0.903, p = 0.035). Severe adverse events due to cilostazol administration did not occur during the study period. Conclusions: Cilostazol administration is effective in preventing sVS and improving outcomes without severe adverse events. A larger-scale study including more cases was necessary to confirm this efficacy of cilostazol.

scholarly journals Risk factors for cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 598-604
Author(s):  
Valentina Opancina ◽  
Snezana Lukic ◽  
Slobodan Jankovic ◽  
Radisa Vojinovic ◽  
Milan Mijailovic
Keyword(s):  
Risk Factors ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Medical Center ◽  
White Blood Cells ◽  
Cerebral Aneurysms ◽  
International Normalized Ratio ◽  
Cross Sectional Study ◽  
Cross Sectional

AbstractIntroductionAneurysmal subarachnoid hemorrhage is a type of spontaneous hemorrhagic stroke, which is caused by a ruptured cerebral aneurysm. Cerebral vasospasm (CVS) is the most grievous complication of subarachnoid hemorrhage (SAH). The aim of this study was to examine the risk factors that influence the onset of CVS that develops after endovascular coil embolization of a ruptured aneurysm.Materials and methodsThe study was designed as a cross-sectional study. The patients included in the study were 18 or more years of age, admitted within a period of 24 h of symptom onset, diagnosed and treated at a university medical center in Serbia during a 5-year period.ResultsOur study showed that the maximum recorded international normalized ratio (INR) values in patients who were not receiving anticoagulant therapy and the maximum recorded white blood cells (WBCs) were strongly associated with cerebrovascular spasm, increasing its chances 4.4 and 8.4 times with an increase of each integer of the INR value and 1,000 WBCs, respectively.ConclusionsSAH after the rupture of cerebral aneurysms creates an endocranial inflammatory state whose intensity is probably directly related to the occurrence of vasospasm and its adverse consequences.

scholarly journals Developmental cannabidiol exposure increases anxiety and modifies genome-wide brain DNA methylation in adult female mice

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Nicole M. Wanner ◽  
Mathia Colwell ◽  
Chelsea Drown ◽  
Christopher Faulk
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Coat Color ◽  
Brain Regions ◽  
Functional Enrichment ◽  
Positive Effects ◽  
Genome Wide ◽  
Nulliparous Female ◽  
The Impact ◽  
The Brain

Abstract Background Use of cannabidiol (CBD), the primary non-psychoactive compound found in cannabis, has recently risen dramatically, while relatively little is known about the underlying molecular mechanisms of its effects. Previous work indicates that direct CBD exposure strongly impacts the brain, with anxiolytic, antidepressant, antipsychotic, and other effects being observed in animal and human studies. The epigenome, particularly DNA methylation, is responsive to environmental input and can direct persistent patterns of gene regulation impacting phenotype. Epigenetic perturbation is particularly impactful during embryogenesis, when exogenous exposures can disrupt critical resetting of epigenetic marks and impart phenotypic effects lasting into adulthood. The impact of prenatal CBD exposure has not been evaluated; however, studies using the psychomimetic cannabinoid Δ9-tetrahydrocannabinol (THC) have identified detrimental effects on psychological outcomes in developmentally exposed adult offspring. We hypothesized that developmental CBD exposure would have similar negative effects on behavior mediated in part by the epigenome. Nulliparous female wild-type Agouti viable yellow (Avy) mice were exposed to 20 mg/kg CBD or vehicle daily from two weeks prior to mating through gestation and lactation. Coat color shifts, a readout of DNA methylation at the Agouti locus in this strain, were measured in F1 Avy/a offspring. Young adult F1 a/a offspring were then subjected to tests of working spatial memory and anxiety/compulsive behavior. Reduced-representation bisulfite sequencing was performed on both F0 and F1 cerebral cortex and F1 hippocampus to identify genome-wide changes in DNA methylation for direct and developmental exposure, respectively. Results F1 offspring exposed to CBD during development exhibited increased anxiety and improved memory behavior in a sex-specific manner. Further, while no significant coat color shift was observed in Avy/a offspring, thousands of differentially methylated loci (DMLs) were identified in both brain regions with functional enrichment for neurogenesis, substance use phenotypes, and other psychologically relevant terms. Conclusions These findings demonstrate for the first time that despite positive effects of direct exposure, developmental CBD is associated with mixed behavioral outcomes and perturbation of the brain epigenome.

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