Localized Brain Tissue Cooling for Use During Intracranial Thrombectomy

2012 ◽  
Author(s):  
Thomas L. Merrill ◽  
Denise R. Merrill ◽  
Jennifer E. Akers
Keyword(s):  
Ischemic Stroke ◽  
Reperfusion Injury ◽  
Brain Tissue ◽  
Ischemic Injury ◽  
Blood Perfusion ◽  
Neuroprotective Agents ◽  
Tissue Necrosis ◽  
Stroke Treatment ◽  
Neurological Outcomes

The primary goal of current ischemic stroke treatment is quickly restoring blood perfusion. Recanalization is linked to improved neurological outcomes [1]. Resulting tissue necrosis, however, following a stroke has two causes: 1) ischemic injury and 2) reperfusion injury. Therefore, development of neuroprotective agents specifically beneficial against reperfusion injury are required.

scholarly journals Top Priorities for Cerebroprotective Studies: A Paradigm Shift

Stroke ◽  
2021 ◽  
Author(s):  
Patrick Lyden ◽  
Alastair Buchan ◽  
Johannes Boltze ◽  
Marc Fisher ◽  
Keyword(s):  
Ischemic Stroke ◽  
Brain Tissue ◽  
Imaging Techniques ◽  
Neurovascular Unit ◽  
Clinical Trial Design ◽  
Clinical Work ◽  
Brain Regions ◽  
Tissue Imaging ◽  
Health Concern ◽  
Stroke Treatment

Despite years of basic research and pioneering clinical work, ischemic stroke remains a major public health concern. Prior STAIR (Stroke Treatment Academic Industry Roundtable) conferences identified both failures of clinical trial design and failures in preclinical assessment in developing putative ischemic stroke treatments. At STAIR XI, participants in workshop no. 1 Top Priorities for Neuroprotection sought to redefine the neuroprotection paradigm and given the paucity of evidence underlying preclinical assessment, offer consensus-based recommendations. STAIR proposes the term brain cytoprotection or cerebroprotection to replace the term neuroprotection when the intention of an investigation is to demonstrate that a new, candidate treatment benefits the entire brain. Although “time is still brain,” tissue imaging techniques have been developed to identify patients with both predicted core injury and penumbral, salvageable brain tissue, regardless of time after stroke symptom onset. STAIR XI workshop participants called this imaging approach a tissue window to select patients for recanalization. Elements of the neurovascular unit show differential vulnerability evolving over differing time scales in different brain regions. STAIR proposes the term target window to suggest therapies that target the different elements of the neurovascular unit at different times. Based on contemporary principles of rigor and transparency, the workshop updated, revised, and enhanced the STAIR preclinical recommendations for developing new treatments in 2 phases: an exploratory qualification phase and a definitive validation phase. For new, putative treatments, investigators should carefully characterize the mechanism of action, the pharmacokinetics/pharmacodynamics, demonstrate target engagement, and confirm penetration through the blood-brain barrier. Before clinical trials, testing of candidate molecules in stroke models could proceed in a comprehensive manner using animals of both sexes and to include significant variables such as age and comorbid conditions. Comprehensive preclinical assessment might include multicenter, collaborative testing, for example, network trials. In the absence of a proven cerebroprotective agent to use as a gold standard, however, it remains speculative whether such comprehensive preclinical assessment can effectively predict clinical outcome.

scholarly journals Lipids and Lipid Mediators Associated with the Risk and Pathology of Ischemic Stroke

2020 ◽  
Vol 21 (10) ◽  
pp. 3618 ◽  
Author(s):  
Anna Kloska ◽  
Marcelina Malinowska ◽  
Magdalena Gabig-Cimińska ◽  
Joanna Jakóbkiewicz-Banecka
Keyword(s):  
Fatty Acids ◽  
Ischemic Stroke ◽  
Brain Tissue ◽  
Lipid Mediators ◽  
Normal Brain ◽  
Stroke Treatment ◽  
Post Stroke ◽  
Increased Risk ◽  
Risk Biomarkers ◽  
And Function

Stroke is a severe neurological disorder in humans that results from an interruption of the blood supply to the brain. Worldwide, stoke affects over 100 million people each year and is the second largest contributor to disability. Dyslipidemia is a modifiable risk factor for stroke that is associated with an increased risk of the disease. Traditional and non-traditional lipid measures are proposed as biomarkers for the better detection of subclinical disease. In the central nervous system, lipids and lipid mediators are essential to sustain the normal brain tissue structure and function. Pathways leading to post-stroke brain deterioration include the metabolism of polyunsaturated fatty acids. A variety of lipid mediators are generated from fatty acids and these molecules may have either neuroprotective or neurodegenerative effects on the post-stroke brain tissue; therefore, they largely contribute to the outcome and recovery from stroke. In this review, we provide an overview of serum lipids associated with the risk of ischemic stroke. We also discuss the role of lipid mediators, with particular emphasis on eicosanoids, in the pathology of ischemic stroke. Finally, we summarize the latest research on potential targets in lipid metabolic pathways for ischemic stroke treatment and on the development of new stroke risk biomarkers for use in clinical practice.

scholarly journals Acute Reperfusion Therapies for Acute Ischemic Stroke

2021 ◽  
Vol 10 (16) ◽  
pp. 3677
Author(s):  
Rajeel Imran ◽  
Ghada A Mohamed ◽  
Fadi Nahab
Keyword(s):  
Ischemic Stroke ◽  
Acute Stroke ◽  
Acute Ischemic Stroke ◽  
Ischemic Injury ◽  
Stroke Treatment ◽  
Tremendous Progress ◽  
Acute Stroke Treatment

The field of acute stroke treatment has made tremendous progress in reducing the overall burden of disability. Understanding the pathophysiology of acute ischemic injury, neuroimaging to quantify the extent of penumbra and infarction, and acute stroke reperfusion therapies have together contributed to these advancements. In this review we highlight advancements in reperfusion therapies for acute ischemic stroke.

scholarly journals Mechanism of Endoplasmic Reticulum Stress in Cerebral Ischemia

2021 ◽  
Vol 15 ◽  
Author(s):  
Yu Han ◽  
Mei Yuan ◽  
Yi-Sha Guo ◽  
Xin-Ya Shen ◽  
Zhen-Kun Gao ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Synthesis ◽  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Er Stress ◽  
Cell Fate ◽  
Ischemic Injury ◽  
Adaptive Procedure ◽  
Protection Mechanism ◽  
Stroke Treatment

Endoplasmic reticulum (ER) is the main organelle for protein synthesis, trafficking and maintaining intracellular Ca2+ homeostasis. The stress response of ER results from the disruption of ER homeostasis in neurological disorders. Among these disorders, cerebral ischemia is a prevalent reason of death and disability in the world. ER stress stemed from ischemic injury initiates unfolded protein response (UPR) regarded as a protection mechanism. Important, disruption of Ca2+ homeostasis resulted from cytosolic Ca2+ overload and depletion of Ca2+ in the lumen of the ER could be a trigger of ER stress and the misfolded protein synthesis. Brain cells including neurons, glial cells and endothelial cells are involved in the complex pathophysiology of ischemic stroke. This is generally important for protein underfolding, but even more for cytosolic Ca2+ overload. Mild ER stress promotes cells to break away from danger signals and enter the adaptive procedure with the activation of pro-survival mechanism to rescue ischemic injury, while chronic ER stress generally serves as a detrimental role on nerve cells via triggering diverse pro-apoptotic mechanism. What’s more, the determination of some proteins in UPR during cerebral ischemia to cell fate may have two diametrically opposed results which involves in a specialized set of inflammatory and apoptotic signaling pathways. A reasonable understanding and exploration of the underlying molecular mechanism related to ER stress and cerebral ischemia is a prerequisite for a major breakthrough in stroke treatment in the future. This review focuses on recent findings of the ER stress as well as the progress research of mechanism in ischemic stroke prognosis provide a new treatment idea for recovery of cerebral ischemia.

scholarly journals Systemic Neutrophil Activation in a Mouse Model of Ischemic Stroke and Reperfusion

2010 ◽  
Vol 13 (2) ◽  
pp. 154-163 ◽  
Author(s):  
Helena Morrison ◽  
Dana McKee ◽  
Leslie Ritter
Keyword(s):  
Ischemic Stroke ◽  
Mouse Model ◽  
Reperfusion Injury ◽  
Brain Tissue ◽  
Mouse Models ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Neutrophil Activation ◽  
Cd11b Expression

As a natural response to injury and disease, neutrophils activate, adhere to the microvasculature, migrate into brain tissue, and release toxic substances such as reactive oxygen species and proteases. This neutrophil response occurs when blood flow is returned to brain tissue (reperfusion) after ischemic stroke. Thus, the presence of activated systemic neutrophils increases the potential for tissue injury during reperfusion after ischemic stroke. Although experiments in rat models suggest that activated neutrophils play a pivotal role in cerebral ischemia reperfusion injury, little is known about systemic neutrophil activation during reperfusion following ischemic stroke in a mouse model. The purpose of this study was to characterize systemic leukocyte responses and neutrophil CD11b expression 15-min and 24-hr post-reperfusion in a mouse model of ischemic stroke. The intraluminal filament method of transient middle cerebral artery occlusion (tMCAO) with reperfusion or a sham procedure was performed in male C57Bl/6 mice. Automated leukocyte counts and manual white blood cell (WBC) differential counts were measured. Flow cytometry was used to assess systemic neutrophil surface CD11b expression. The data suggest that the damaging potential of systemic neutrophil activation begins as early as 15 min and remains evident at 24 hr after the initiation of reperfusion. In addition, because transgenic mouse models, bred on a C57Bl/6 background, are increasingly used to elucidate single mechanisms of reperfusion injury after ischemic stroke, findings from this study are foundational for future investigations examining the damaging potential of neutrophil responses post-reperfusion after ischemic stroke in genetically altered mouse models within this background strain.

Cerebral Ischemic Reperfusion Injury Following Recanalization of Large Vessel Occlusions

Neurosurgery ◽  
2017 ◽  
Vol 82 (6) ◽  
pp. 781-789 ◽  
Author(s):  
Fawaz Al-Mufti ◽  
Krishna Amuluru ◽  
William Roth ◽  
Rolla Nuoman ◽  
Mohammad El-Ghanem ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Reperfusion Injury ◽  
Large Artery ◽  
Stroke Patients ◽  
Ischemic Reperfusion Injury ◽  
Stroke Treatment ◽  
Ischemic Reperfusion ◽  
Cerebral Ischemic ◽  
Cerebral Ischemic Reperfusion

Abstract Although stroke has recently dropped to become the nation's fifth leading cause of mortality, it remains the top leading cause of morbidity and disability in the US. Recent advances in stroke treatment, including intravenous fibrinolysis and mechanical thromboembolectomy, allow treatment of a greater proportion of stroke patients than ever before. While intra-arterial fibrinolysis with recombinant tissue plasminogen is an effective for treatment of a broad range of acute ischemic strokes, endovascular mechanical thromboembolectomy procedures treat severe strokes due to large artery occlusions, often resistant to intravenous drug. Together, these procedures result in a greater proportion of revascularized stroke patients than ever before, up to 88% in 1 recent trial (EXTEND-IA). Subsequently, there is a growing need for neurointensivists to develop more effective strategies to manage stroke patients following successful reperfusion. Cerebral ischemic reperfusion injury (CIRI) is defined as deterioration of brain tissue suffered from ischemia that concomitantly reverses the benefits of re-establishing cerebral blood flow following mechanical or chemical therapies for acute ischemic stroke. Herein, we examine the pathophysiology of CIRI, imaging modalities, and potential neuroprotective strategies. Additionally, we sought to lay down a potential treatment approach for patients with CIRI following emergent endovascular recanalization for acute ischemic stroke.

Mechanical thrombectomy in pediatric stroke: systematic review, individual patient data meta-analysis, and case series

2019 ◽  
Vol 24 (5) ◽  
pp. 558-571 ◽  
Author(s):  
Kartik Bhatia ◽  
Hans Kortman ◽  
Christopher Blair ◽  
Geoffrey Parker ◽  
David Brunacci ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Mechanical Thrombectomy ◽  
Case Reports ◽  
Meta Analysis ◽  
Case Series ◽  
Neurological Outcomes

OBJECTIVEThe role of mechanical thrombectomy in pediatric acute ischemic stroke is uncertain, despite extensive evidence of benefit in adults. The existing literature consists of several recent small single-arm cohort studies, as well as multiple prior small case series and case reports. Published reports of pediatric cases have increased markedly since 2015, after the publication of the positive trials in adults. The recent AHA/ASA Scientific Statement on this issue was informed predominantly by pre-2015 case reports and identified several knowledge gaps, including how young a child may undergo thrombectomy. A repeat systematic review and meta-analysis is warranted to help guide therapeutic decisions and address gaps in knowledge.METHODSUsing PRISMA-IPD guidelines, the authors performed a systematic review of the literature from 1999 to April 2019 and individual patient data meta-analysis, with 2 independent reviewers. An additional series of 3 cases in adolescent males from one of the authors’ centers was also included. The primary outcomes were the rate of good long-term (mRS score 0–2 at final follow-up) and short-term (reduction in NIHSS score by ≥ 8 points or NIHSS score 0–1 at up to 24 hours post-thrombectomy) neurological outcomes following mechanical thrombectomy for acute ischemic stroke in patients < 18 years of age. The secondary outcome was the rate of successful angiographic recanalization (mTICI score 2b/3).RESULTSThe authors’ review yielded 113 cases of mechanical thrombectomy in 110 pediatric patients. Although complete follow-up data are not available for all patients, 87 of 96 (90.6%) had good long-term neurological outcomes (mRS score 0–2), 55 of 79 (69.6%) had good short-term neurological outcomes, and 86 of 98 (87.8%) had successful angiographic recanalization (mTICI score 2b/3). Death occurred in 2 patients and symptomatic intracranial hemorrhage in 1 patient. Sixteen published thrombectomy cases were identified in children < 5 years of age.CONCLUSIONSMechanical thrombectomy may be considered for acute ischemic stroke due to large vessel occlusion (ICA terminus, M1, basilar artery) in patients aged 1–18 years (Level C evidence; Class IIb recommendation). The existing evidence base is likely affected by selection and publication bias. A prospective multinational registry is recommended as the next investigative step.

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