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Biomarker Application for Precision Medicine in Stroke
AbstractStroke remains one of the leading causes of long-term disability and mortality despite recent advances in acute thrombolytic therapies. In fact, the global lifetime risk of stroke in adults over the age of 25 is approximately 25%, with 24.9 million cases of ischemic stroke and 18.7 million cases of hemorrhagic stroke reported in 2015. One of the main challenges in developing effective new acute therapeutics and enhanced long-term interventions for stroke recovery is the heterogeneity of stroke, including etiology, comorbidities, and lifestyle factors that uniquely affect each individual stroke survivor. In this com...
Source: Translational Stroke Research - December 17, 2019 Category: Neurology Source Type: research

The Role of Thrombin in Brain Injury After Hemorrhagic and Ischemic Stroke
AbstractThrombin is increased in the brain after hemorrhagic and ischemic stroke primarily due to the prothrombin entry from blood either with a hemorrhage or following blood-brain barrier disruption. Increasing evidence indicates that thrombin and its receptors (protease-activated receptors (PARs)) play a major role in brain pathology following ischemic and hemorrhagic stroke (including intracerebral, intraventricular, and subarachnoid hemorrhage). Thrombin and PARs affect brain injury via multiple mechanisms that can be detrimental or protective. The cleavage of prothrombin into thrombin is the key step of hemostasis and...
Source: Translational Stroke Research - April 20, 2021 Category: Neurology Source Type: research

Development of Machine Learning Models to Predict Probabilities and Types of Stroke at Prehospital Stage: the Japan Urgent Stroke Triage Score Using Machine Learning (JUST-ML)
AbstractIn conjunction with recent advancements in machine learning (ML), such technologies have been applied in various fields owing to their high predictive performance. We tried to develop prehospital stroke scale with ML. We conducted multi-center retrospective and prospective cohort study. The training cohort had eight centers in Japan from June 2015 to March 2018, and the test cohort had 13 centers from April 2019 to March 2020. We use the three different ML algorithms (logistic regression, random forests, XGBoost) to develop models. Main outcomes were large vessel occlusion (LVO), intracranial hemorrhage (ICH), suba...
Source: Translational Stroke Research - August 14, 2021 Category: Neurology Source Type: research

A Non-Human Primate Model of Aneurismal Subarachnoid Hemorrhage (SAH)
We present the model characteristics and describe in details medical, surgical, imagining techniques that we have used at the Surgical Neurology Branch of the National Institute of Neurological Disorders and Stroke from 1989.
Source: Translational Stroke Research - September 14, 2014 Category: Neurology Source Type: research

ASPECT Score and Its Application to Vasospasm in Aneurysmal Subarachnoid Haemorrhage: a Case –Control Study
AbstractDelayed cerebral ischaemia (DCI) is a significant complication of aneurysmal subarachnoid haemorrhage (aSAH) and is strongly associated with poorer outcome. The Alberta Stroke Program Early Computer Tomography (ASPECT) score is an established scoring tool, used in acute ischaemic stroke, to quantify early ischaemic changes on CT head scans. We aim to identify if ASPECT scoring correlates with functional outcome in DCI following aSAH. Retrospective case –control study. Inclusion criteria: admission to the Department of Neurosurgery at Leeds Teaching Hospitals NHS Trust (a tertiary neurosurgical centre in the Unite...
Source: Translational Stroke Research - August 9, 2022 Category: Neurology Source Type: research

The Rabbit Shunt Model of Subarachnoid Haemorrhage
Abstract Aneurysmal subarachnoid haemorrhage (SAH) is a disease with devastating complications that leads to stroke, permanent neurological deficits and death. Clinical and ex-perimental work has demonstrated the importance of the contribution of delayed cerebral vasospasm (DCVS) indepen-dent early events to mortality, morbidity and functional out-come after SAH. In order to elucidate processes involved in early brain injury (EBI), animal models that reflect acute events of aneurysmal bleeding, such as increase in intracranial pressure (ICP) and decrease in cerebral perfusion pressure, are needed. In the presented...
Source: Translational Stroke Research - October 19, 2014 Category: Neurology Source Type: research

Brainstem Opioidergic System Is Involved in Early Response to Experimental SAH
In this study, we have demonstrated that ablation of μ-opioid receptor containing cells with dermorphin conjugates in the RVM results in a high mortality rate after experimental SAH and, in survivors, causes a dramatic decrease in CBF. Further, locally blocking the μ-opioid receptor with the antagonist naltrexone attenuated the reduction in CBF secondary to experimental SAH. Saturating μ-opioid receptors with the agonist [d-Ala(2),NMe-Phe(4),Gly-ol(5)]-encephalin (DAMGO) had no effect. Taken together, these results suggest that SAH activates opioidergic signaling in the RVM with a resultant reduction in CBF. Further, ce...
Source: Translational Stroke Research - November 25, 2014 Category: Neurology Source Type: research

Matched Cohort Analysis of the Effects of Limb Remote Ischemic Conditioning in Patients with Aneurysmal Subarachnoid Hemorrhage
In this study, we aim to detect the potential effect of an established lower-limb conditioning protocol on clinical outcomes of aSAH patients. Neurologic outcome (modified Rankin Scale (mRS)) of patients enrolled in a prospective trial (RIPC-SAH) was measured. A matching algorithm was applied to identify control patients with aSAH from an institutional departmental database. RIC patients underwent four lower-limb conditioning sessions, consisting of four 5-min cycles per session over nonconsecutive days. Good functional outcome was defined as mRS of 0 to 2. The study population consisted of 21 RIC patients and 61 matched c...
Source: Translational Stroke Research - December 2, 2015 Category: Neurology Source Type: research

Apolipoprotein E Exerts a Whole-Brain Protective Property by Promoting M1? Microglia Quiescence After Experimental Subarachnoid Hemorrhage in Mice
We reported thatApoe deficiency resulted in a more extensive EBI at 48  h after SAH in mice demonstrated by MRI scanning and immunohistochemical staining and exhibited more extensive white matter injury and neuronal apoptosis than WT mice. These changes were associated with an increase in NADPH oxidase 2 (NOX2) expression, an important regulator of both oxidative stre ss and inflammatory cytokines. Furthermore, immunohistochemical analysis revealed that NOX2 was abundantly expressed in activated M1 microglia. The JAK2/STAT3 signaling pathway, an upstream regulator of NOX2, was increased in WT mice and activated to an even...
Source: Translational Stroke Research - September 17, 2018 Category: Neurology Source Type: research

TREM-1 Exacerbates Neuroinflammatory Injury via NLRP3 Inflammasome-Mediated Pyroptosis in Experimental Subarachnoid Hemorrhage
In conclusion, our results revealed the critical role of TREM-1 in neuroinflammation following SAH, suggesting that TREM-1 inhibition might be a potential therapeutic approach for SAH.
Source: Translational Stroke Research - August 29, 2020 Category: Neurology Source Type: research

Predictors and Outcomes of Neurological Deterioration in Intracerebral Hemorrhage: Results from the TICH-2 Randomized Controlled Trial
AbstractNeurological deterioration is common after intracerebral hemorrhage (ICH). We aimed to identify the predictors and effects of neurological deterioration and whether tranexamic acid reduced the risk of neurological deterioration. Data from the Tranexamic acid in IntraCerebral Hemorrhage-2 (TICH-2) randomized controlled trial were analyzed. Neurological deterioration was defined as an increase in National Institutes of Health Stroke Scale (NIHSS) of ≥ 4 or a decline in Glasgow Coma Scale of ≥ 2. Neurological deterioration was considered to be early if it started ≤ 48 h and late if commenced between 48 h...
Source: Translational Stroke Research - September 8, 2020 Category: Neurology Source Type: research

Blocking Hepatoma-Derived Growth Factor Attenuates Vasospasm and Neuron Cell Apoptosis in Rats Subjected to Subarachnoid Hemorrhage
This study explored the relationship between SAH and HDGF. Sixty rats were divided into five groups (n  = 12/group): (A) control group; (B) rHDGF ab only group [normal animals treated with 50 µM recombinant HDGF antibodies (rHDGF ab)]; (C) SAH group; (D) SAH + pre-rHDGF ab group (SAH animals pre-treated with 50 µM rHDGF ab into the subarachnoid space within 24 h before SAH); and (E) SAH  + post-rHDGF ab group (SAH animals post-treated with 50 µM rHDGF ab into the subarachnoid space within 24 h after SAH). At 48 h after SAH, serum and cerebrospinal fluid (CSF) samples were collected to measure the level...
Source: Translational Stroke Research - July 5, 2021 Category: Neurology Source Type: research

A Systematic Review of Inflammatory Cytokine Changes Following Aneurysmal Subarachnoid Hemorrhage in Animal Models and Humans
AbstractAneurysmal subarachnoid hemorrhage (aSAH) is a severe form of stroke that occurs following rupture of a cerebral aneurysm. Acute inflammation and secondary delayed inflammatory responses, both largely controlled by cytokines, work together to create high mortality and morbidity for this group. The trajectory and time course of cytokine change must be better understood in order to effectively manage unregulated inflammation and improve patient outcomes following aSAH. A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Three different se...
Source: Translational Stroke Research - March 9, 2022 Category: Neurology Source Type: research

Neutrophil Extracellular Traps (NETs): A New Therapeutic Target for Neuroinflammation and Microthrombosis After Subarachnoid Hemorrhage?
AbstractNeutrophil extracellular traps (NETs) play a major role in intrinsic immunity by limiting and killing pathogens. Recently, a series of studies have confirmed that NETs are closely associated with vascular injury and microthrombosis. Furthermore, NETs play an important role in neuroinflammation after ischemic and hemorrhagic stroke. Neuroinflammation and microthrombosis after subarachnoid hemorrhage are key pathophysiological processes associated with poor prognosis, but their crucial formation mechanisms and interventions remain to be elucidated. Could NETs, as an emerging and important pathogenesis, be a new thera...
Source: Translational Stroke Research - June 11, 2022 Category: Neurology Source Type: research

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