scholarly journals The Role of Microclot Formation in an Acute Subarachnoid Hemorrhage Model in the Rabbit

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Lukas Andereggen ◽  
Volker Neuschmelting ◽  
Michael von Gunten ◽  
Hans Rudolf Widmer ◽  
Javier Fandino ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Neuronal Apoptosis ◽  
Structural Changes ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Rabbit Model ◽  
Microvascular Dysfunction ◽  
Early Brain Injury ◽  
Brain Parenchyma ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Acute Subarachnoid Hemorrhage

Background.Microvascular dysfunction and microthrombi formation are believed to contribute to development of early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (SAH).Objective.This study aimed to determine (i) extent of microthrombus formation and neuronal apoptosis in the brain parenchyma using a blood shunt SAH model in rabbits; (ii) correlation of structural changes in microvessels with EBI characteristics.Methods.Acute SAH was induced using a rabbit shunt cisterna magna model. Extent of microthrombosis was detected 24 h post-SAH (n=8) by fibrinogen immunostaining, compared to controls (n=4). We assessed apoptosis by terminal deoxynucleotidyl transferase nick end labeling (TUNEL) in cortex and hippocampus.Results.Our results showed significantly more TUNEL-positive cells (SAH: 115 ± 13; controls: 58 ± 10;P=0.016) and fibrinogen-positive microthromboemboli (SAH: 9 ± 2; controls: 2 ± 1;P=0.03) in the hippocampus after aneurysmal SAH.Conclusions.We found clear evidence of early microclot formation in a rabbit model of acute SAH. The extent of microthrombosis did not correlate with early apoptosis or CPP depletion after SAH; however, the total number of TUNEL positive cells in the cortex and the hippocampus significantly correlated with mean CPP reduction during the phase of maximum depletion after SAH induction. Both microthrombosis and neuronal apoptosis may contribute to EBI and subsequent DCI.

scholarly journals TRAF3 mediates neuronal apoptosis in early brain injury following subarachnoid hemorrhage via targeting TAK1-dependent MAPKs and NF-κB pathways

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yan Zhou ◽  
Tao Tao ◽  
Guangjie Liu ◽  
Xuan Gao ◽  
Yongyue Gao ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Therapeutic Target ◽  
Cortical Neurons ◽  
Neuronal Apoptosis ◽  
Early Brain Injury ◽  
Neurological Deficits ◽  
Human Brain Tissue

AbstractNeuronal apoptosis has an important role in early brain injury (EBI) following subarachnoid hemorrhage (SAH). TRAF3 was reported as a promising therapeutic target for stroke management, which covered several neuronal apoptosis signaling cascades. Hence, the present study is aimed to determine whether downregulation of TRAF3 could be neuroprotective in SAH-induced EBI. An in vivo SAH model in mice was established by endovascular perforation. Meanwhile, primary cultured cortical neurons of mice treated with oxygen hemoglobin were applied to mimic SAH in vitro. Our results demonstrated that TRAF3 protein expression increased and expressed in neurons both in vivo and in vitro SAH models. TRAF3 siRNA reversed neuronal loss and improved neurological deficits in SAH mice, and reduced cell death in SAH primary neurons. Mechanistically, we found that TRAF3 directly binds to TAK1 and potentiates phosphorylation and activation of TAK1, which further enhances the activation of NF-κB and MAPKs pathways to induce neuronal apoptosis. Importantly, TRAF3 expression was elevated following SAH in human brain tissue and was mainly expressed in neurons. Taken together, our study demonstrates that TRAF3 is an upstream regulator of MAPKs and NF-κB pathways in SAH-induced EBI via its interaction with and activation of TAK1. Furthermore, the TRAF3 may serve as a novel therapeutic target in SAH-induced EBI.

Apigenin attenuates oxidative stress and neuronal apoptosis in early brain injury following subarachnoid hemorrhage

2017 ◽  
Vol 40 ◽  
pp. 157-162 ◽  
Author(s):  
Yuwei Han ◽  
Tingting Zhang ◽  
Jingyuan Su ◽  
Yuan Zhao ◽  
Chenchen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Neuronal Apoptosis ◽  
Early Brain Injury

Abstract W P307: Novel Application of Reversible Parental Anti-platelets in Patients with Aneurysmal Subarachnoid Hemorrhage

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Siddhart Mehta ◽  
Mohammed Hussain ◽  
Jaskiran Brar ◽  
Daniel Korya ◽  
Harina Chahal ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Coil Embolization ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Antiplatelet Agents ◽  
Endovascular Coiling ◽  
International Subarachnoid Aneurysm Trial ◽  
Procedural Complications ◽  
Acute Subarachnoid Hemorrhage ◽  
Comprehensive Stroke Center ◽  
Stroke Center

Background and Objective: The International Subarachnoid Aneurysm Trial (ISAT) showed a greater likelihood of survival free 1 year disability in patients undergoing endovascular coiling who were started on antiplatelet agents after SAH compared to ones undergoing neurosurgical clipping. However, data on safety of acute parental antiplatelet agents after aneurysmal coiling is lacking. We report on the safety of IV Eptifibatide (rapidly reversible Glyprotein IIbIIIa inhibitor) on patients presenting with acute subarachnoid hemorrhage undergoing endovascular coiling for aneurysmal embolization. Methods: All the patients from 2009-13 who presented to our university affiliated comprehensive stroke center with aneurysmal subarachnoid hemorrhage and underwent endovascular coiling were included for the study. Patients that received IV Eptifibatide for various reasons including acute need for stent assist coiling after securing the ruptured aneurysm with endovascular coiling were reviewed. Eptifibatide was administered intra-arterially as a 135-μg/kg single-dose bolus, and then continued on intravenous infusion of 0.5-μg/kg/min post-procedurally. Charts were reviewed for all patients to assess for medical/procedural complications including symptomatic and asymptomatic intra- and extra-cranial hemorrhages, groin hematomas, epistaxis and gross hematuria. Results: Of the total of 93 patients treated with coil embolization during this period, 5 patients (mean age 56 years, 20% male [n=1]) received acute intra-procedural Eptifibatide followed by IV infusion for a mean duration of 77 hours (range 20-130 hours). Various reasons for use of Eptifibatide included: stent assist coiling [n=2], multiple stents for flow diversion [n=1], partial coil prolapse [n=1] and vascular lumen flow compromise [n=1]. None of the patients demonstrated symptomatic/asymptomatic hemorrhage, groin hematoma, epistaxis or hematuria. Conclusion: Our results may highlight safety of administering IV Eptifibatide to prevent thrombotic complications after endovascular coil embolization in select patients with aneurysmal subarachnoid hemorrhage. Multicenter prospective trials are warranted to corroborate our findings.

The neutrophil enzyme myeloperoxidase directly modulates neuronal response after subarachnoid hemorrhage, a sterile injury model

2020 ◽  
Author(s):  
Aminata P. Coulibaly ◽  
Pinar Pezuk ◽  
Paul Varghese ◽  
William Gartman ◽  
Danielle Triebwasser ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cognitive Deficits ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Neuronal Response ◽  
Neutrophil Infiltration ◽  
Brain Parenchyma ◽  
Biologically Active ◽  
Cns Injury ◽  
And Function ◽  
The Brain

Abstract Background: Aneurysmal subarachnoid hemorrhage (SAH) is associated with the development of delayed cognitive deficits. Neutrophil infiltration into the central nervous system (CNS) is linked to the development of these deficits after SAH. It is however unclear how neutrophil activity, direct or indirect, influences CNS function in SAH. As such, the present project aims to elucidate neutrophil factors and mechanisms mediating CNS injury and cognitive deficits after SAH. Methods: Using a murine model of SAH and mice deficient in neutrophil effector functions, we determined which neutrophil effector function is critical to the development of deficits after SAH. Also, in vitro techniques were used to elucidate whether neutrophils directly or indirectly affect neuronal function after SAH. Results: Our results show that following SAH, neutrophils infiltrate the meninges, and not the brain parenchyma. Mice lacking functional myeloperoxidase (MPO KO), a neutrophil enzyme, lack both the meningeal neutrophil infiltration and the cognitive deficits associated with SAH. The re-introduction of biologically active MPO, and its substrate hydrogen peroxide, to the cerebrospinal fluid of MPO KO mice at the time of hemorrhage restores the spatial memory deficit observed after SAH. Furthermore, MPO directly affects the function of both primary neurons and astrocytes in culture. Neurons exposed to MPO and its substrate show decreased calcium activity at baseline and after stimulation with potassium chloride. In addition, MPO and its substrate lead to significant astrocyte loss in culture, phenocopying a result observed in the brain after SAH. Conclusions: These results implicate MPO as a mediator of neuronal dysfunction in SAH through direct effect on both neurons and astrocytes. Finally, these results show that, in SAH, the activity of innate immune cells in the meninges can modulate the activity and function of the underlying brain tissue.

Clinical Use of a Portable Bedside Cerebral Blood Flow Machine in the Management of Aneurysmal Subarachnoid Hemorrhage

Neurosurgery ◽  
1984 ◽  
Vol 15 (4) ◽  
pp. 519-525 ◽  
Author(s):  
Jacob Rosenstein ◽  
Mikio Suzuki ◽  
Lindsay Symon ◽  
Sheila Redmond
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Subarachnoid Hemorrhage ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Initial Slope ◽  
Management Decision ◽  
Mean Flow ◽  
Management Decision Making ◽  
Acute Subarachnoid Hemorrhage ◽  
The Mean

Abstract Recent advances in electronics and microprocessors have enabled the development of a compact portable cerebral blood flow (CBF) machine capable of being transported to the patient's bedside. We have used such a device, the Novo Cerebrograph 2a, during the past 7 months on a regular basis in the day to day management of our patients with intracranial aneurysms. One hundred three studies were performed in 23 cases of suspected intracranial aneurysm. Twenty-two cases presented with acute subarachnoid hemorrhage. Patients were studied on admission, preoperatively, in the recovery room, on postoperative Days 1, 5, and 14, and whenever the clinical condition of the patient warranted. The preoperative admission grade was found to correlate well with the mean CBFisi (ISI: initial slope index). Grade III and IV patients had flows significantly lower than those of Grade I and II patients. Serial CBF measurements proved useful in the management of 18 of 22 cases admitted with acute subarachnoid hemorrhage. Delayed ischemic deficits secondary to vasospasm occurred in 6 cases, with a concomitant average fall in mean flow in the symptomatic hemispheres of 27.9%. After volume expansion, an average increase in flow of 29.7% was noted. Low preoperative flows influenced management decision-making in 8 cases. In a further 4 cases, serial CBF measurements were helpful in the differential diagnosis of new neurological signs.

scholarly journals Non-Ischemic Cerebral Energy Dysfunction at the Early Brain Injury Phase following Aneurysmal Subarachnoid Hemorrhage

2017 ◽  
Vol 8 ◽  
Author(s):  
Laurent Carteron ◽  
Camille Patet ◽  
Daria Solari ◽  
Mahmoud Messerer ◽  
Roy T. Daniel ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Early Brain Injury

scholarly journals The Role of the Blood Neutrophil-to-Lymphocyte Ratio in Aneurysmal Subarachnoid Hemorrhage

2021 ◽  
Vol 12 ◽  
Author(s):  
Lingxin Cai ◽  
Hanhai Zeng ◽  
Xiaoxiao Tan ◽  
Xinyan Wu ◽  
Cong Qian ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Critical Role ◽  
Delayed Cerebral Ischemia ◽  
Early Brain Injury ◽  
Neutrophil To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Novel Therapeutic Strategies ◽  
Improved Accuracy

Aneurysmal subarachnoid hemorrhage (aSAH) is an important type of stroke with the highest rates of mortality and disability. Recent evidence indicates that neuroinflammation plays a critical role in both early brain injury and delayed neural deterioration after aSAH, contributing to unfavorable outcomes. The neutrophil-to-lymphocyte ratio (NLR) is a peripheral biomarker that conveys information about the inflammatory burden in terms of both innate and adaptive immunity. This review summarizes relevant studies that associate the NLR with aSAH to evaluate whether the NLR can predict outcomes and serve as an effective biomarker for clinical management. We found that increased NLR is valuable in predicting the clinical outcome of aSAH patients and is related to the risk of complications such as delayed cerebral ischemia (DCI) or rebleeding. Combined with other indicators, the NLR provides improved accuracy for predicting prognosis to stratify patients into different risk categories. The underlying pathophysiology is highlighted to identify new potential targets for neuroprotection and to develop novel therapeutic strategies.

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