scholarly journals Catheter based selective hypothermia reduces stroke volume during focal cerebral ischemia in swine

2015 ◽  
Vol 8 (4) ◽  
pp. 418-422 ◽  
Author(s):  
Thomas K Mattingly ◽  
Lynn M Denning ◽  
Karen L Siroen ◽  
Barb Lehrbass ◽  
Pablo Lopez-Ojeda ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Stroke Volume ◽  
Acute Ischemic Stroke ◽  
Brain Mri ◽  
Global Cerebral Ischemia ◽  
Moderate Hypothermia ◽  
Stroke Model ◽  
Stroke Treatment ◽  
Endovascular Cooling

BackgroundTotal body hypothermia is an established neuroprotectant in global cerebral ischemia. The role of hypothermia in acute ischemic stroke remains uncertain. Selective application of hypothermia to a region of focal ischemia may provide similar protection with more rapid cooling and elimination of systemic side effects. We studied the effect of selective endovascular cooling in a focal stroke model in adult domestic swine.MethodsAfter craniotomy under general anesthesia, a proximal middle cerebral artery branch was occluded for 3 h, followed by 3 h of reperfusion. In half of the animals, selective hypothermia was induced during reperfusion using a dual lumen balloon occlusion catheter placed in the ipsilateral common carotid artery. Following reperfusion, the animals were sacrificed. Brain MRI and histology were evaluated by experts who were blinded to the intervention.Results25 animals were available for analysis. Using selective hypothermia, hemicranial temperature was successfully cooled to a mean of 26.5°C. Average time from start of perfusion to attainment of moderate hypothermia (<30°C) was 25 min. Mean MRI stroke volumes were significantly reduced by selective cooling (0.050±0.059 control, 0.005±0.011 hypothermia (ratio stroke:hemisphere volume) (p=0.046). Stroke pathology volumes were reduced by 42% compared with controls (p=0.256).ConclusionsSelective moderate hypothermia was rapidly induced using endovascular techniques in a clinically realistic swine stroke model. A significant reduction in stroke volume on MRI was observed. Endovascular selective hypothermia can provide neuroprotection within time frames relevant to acute ischemic stroke treatment.

scholarly journals Fifty Years of Acute Ischemic Stroke Treatment: A Personal History

2021 ◽  
pp. 1-15
Author(s):  
James C. Grotta
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Acute Stroke ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Systems Of Care ◽  
Medical Science ◽  
Tissue Type ◽  
Stroke Units ◽  
Stroke Treatment

<b><i>Background:</i></b> It has been 50 years since the first explorations of the physiology of cerebral ischemia by measuring cerebral blood flow (CBF), and 25 years since the approval of tissue plasminogen activator for treating acute ischemic stroke. My personal career began and matured during those eras. Here, I provide my perspective on the evolution of acute stroke research and treatment from 1971 to the present, with some in-depth discussion of the National Institutes of Neurologic Disease and Stroke (NINDS) tissue-type plasminogen activator (tPA) stroke trial and development of mobile stroke units. <b><i>Summary:</i></b> Studies of CBF and metabolism in acute stroke patients revealed graded tissue injury that was dependent on the duration of ischemia. Subsequent animal research unraveled the biochemical cascade of events occurring at the cellular level after cerebral ischemia. After a decade of failed translation, the development of a relatively safe thrombolytic allowed us to achieve reperfusion and apply the lessons from earlier research to achieve positive clinical results. The successful conduct of the NINDS tPA stroke study coupled with positive outcomes from companion tPA studies around the world created the specialty of vascular neurology. This was followed by an avalanche of research in imaging, a focus on enhancing reperfusion through thrombectomy, and improving delivery of faster treatment culminating in mobile stroke units. <b><i>Key Messages:</i></b> The last half century has seen the birth and evolution of successful acute stroke treatment. More research is needed in developing new drugs and catheters to build on the advances we have already made with reperfusion and also in evolving our systems of care to get more patients treated more quickly in the prehospital setting. The history of stroke treatment over the last 50 years exemplifies that medical “science” is an evolving discipline worth an entire career’s dedication. What was impossible 50 years ago is today’s standard of care, what we claim as dogma today will be laughed at a decade from now, and what appears currently impossible will be tomorrow’s realities.

scholarly journals Human-Albumin Neuroprotection in Acute Ischemic Stroke: Marked Efficacy at Moderate Doses, with a Broad Therapeutic Window.

Stroke ◽  
2001 ◽  
Vol 32 (suppl_1) ◽  
pp. 326-326
Author(s):  
Myron D Ginsberg ◽  
Ludmila Belayev ◽  
Yitao Liu ◽  
Weizhao Zhao ◽  
Raul Busto
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Acute Ischemic Stroke ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Human Albumin ◽  
Global Cerebral Ischemia ◽  
Therapeutic Window ◽  
High Dose ◽  
Neurological Score

58 We have previously shown that high-dose human albumin (Alb) is markedly neuroprotective in focal and global cerebral ischemia and in traumatic brain injury. In this study, we examined the efficacy of moderate, clinically achievable Alb doses and defined the therapeutic window in focal cerebral ischemia. Sprague Dawley rats (n=62) were anesthetized with halothane/nitrous oxide and received 2-h middle cerebral artery occlusion (MCAo) by intraluminal suture. Neurological status was evaluated during occlusion (60 min) and daily for 3 days after MCAo. In the dose-response study, animals were given either 25% Alb in doses 0.63 or 1.25 g/kg , or 0.9% saline vehicle, i.v. immediately after suture removal (n=5 each). In the therapeutic window study, 1.25 g/kg Alb was administered at either 2 h, 3 h, 4 h, or 5 h after onset of stroke (i.e., 0 to 3 h after onset of reperfusion) (n=9–10 ea.). Three days after MCAo, brains were perfusion-fixed, and image-processing was used to compute infarct volumes and brain swelling. Both moderate Alb doses (0.63 and 1.25 g/kg) significantly improved the neurological score compared to vehicle rats at 24h, 48h and 72h; and markedly reduced cortical infarct volume (by 66±14% and 95±4%, respectively), striatal infarct volume (by 54±8% and 52±14%), and total infarct volume (by 58±5% and 67±9%, respectively). Brain edema was virtually eliminated by Alb treatment. In the therapeutic window study, even when treatment was initiated as late as 4 hours after onset of MCAo, 1.25 g/kg Alb led to significantly improved neurological score and highly significant reductions of infarct areas in cortex (68% reduction), subcortical regions (52% reduction), and total infarct (61% reduction). The striking efficacy and broad therapeutic window of moderate-dose Alb therapy in experimental focal ischemia strongly supports the feasibility of initiating early-phase clinical trials of this promising agent in patients with acute ischemic stroke. This work was supported by NIH Grant NS05820 (MDG) and by AHA Initial Investigator Award (LB).

scholarly journals Hypothermic neuroprotection against acute ischemic stroke: The 2019 update

2019 ◽  
Vol 40 (3) ◽  
pp. 461-481 ◽  
Author(s):  
Longfei Wu ◽  
Di Wu ◽  
Tuo Yang ◽  
Jin Xu ◽  
Jian Chen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Acute Ischemic Stroke ◽  
Brain Injuries ◽  
Focal Cerebral Ischemia ◽  
Global Cerebral Ischemia ◽  
Neuroprotective Effects ◽  
Neuroprotective Strategies ◽  
Selective Cooling ◽  
Ischemic Encephalopathy

Acute ischemic stroke is a leading cause of death and disability worldwide. Therapeutic hypothermia has long been considered as one of the most robust neuroprotective strategies. Although the neuroprotective effects of hypothermia have only been confirmed in patients with global cerebral ischemia after cardiac arrest and in neonatal hypoxic ischemic encephalopathy, establishing standardized protocols and strictly controlling the key parameters may extend its application in other brain injuries, such as acute ischemic stroke. In this review, we discuss the potential neuroprotective effects of hypothermia, its drawbacks evidenced in previous studies, and its potential clinical application for acute ischemic stroke especially in the era of reperfusion. Based on the different conditions between bench and bedside settings, we demonstrate the importance of vascular recanalization for neuroprotection of hypothermia by analyzing numerous literatures regarding hypothermia in focal cerebral ischemia. Then, we make a thorough analysis of key parameters of hypothermia and introduce novel hypothermic therapies. We advocate in favor of the process of clinical translation of intra-arterial selective cooling infusion in the era of reperfusion and provide insights into the prospects of hypothermia in acute ischemic stroke.

scholarly journals Selective intra-carotid blood cooling in acute ischemic stroke: A safety and feasibility study in an ovine stroke model

2021 ◽  
pp. 0271678X2110249
Author(s):  
Giorgio FM Cattaneo ◽  
Andrea M Herrmann ◽  
Sebastian A Eiden ◽  
Manuela Wieser ◽  
Elias Kellner ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Carotid Artery ◽  
Acute Ischemic Stroke ◽  
Neurological Outcome ◽  
Artery Occlusion ◽  
Control Group ◽  
Stroke Model ◽  
Primary Endpoints ◽  
Neuroprotective Strategy ◽  
Vessel Patency

Selective therapeutic hypothermia (TH) showed promising preclinical results as a neuroprotective strategy in acute ischemic stroke. We aimed to assess safety and feasibility of an intracarotid cooling catheter conceived for fast and selective brain cooling during endovascular thrombectomy in an ovine stroke model. Transient middle cerebral artery occlusion (MCAO, 3 h) was performed in 20 sheep. In the hypothermia group (n = 10), selective TH was initiated 20 minutes before recanalization, and was maintained for another 3 h. In the normothermia control group (n = 10), a standard 8 French catheter was used instead. Primary endpoints were intranasal cooling performance (feasibility) plus vessel patency assessed by digital subtraction angiography and carotid artery wall integrity (histopathology, both safety). Secondary endpoints were neurological outcome and infarct volumes. Computed tomography perfusion demonstrated MCA territory hypoperfusion during MCAO in both groups. Intranasal temperature decreased by 1.1 °C/3.1 °C after 10/60 minutes in the TH group and 0.3 °C/0.4 °C in the normothermia group (p < 0.001). Carotid artery and branching vessel patency as well as carotid wall integrity was indifferent between groups. Infarct volumes (p = 0.74) and neurological outcome (p = 0.82) were similar in both groups. Selective TH was feasible and safe. However, a larger number of subjects might be required to demonstrate efficacy.

scholarly journals Cerebral endothelial cell-derived small extracellular vesicles enhance neurovascular function and neurological recovery in rat acute ischemic stroke models of mechanical thrombectomy and embolic stroke treatment with tPA

2021 ◽  
pp. 0271678X2199298
Author(s):  
Chao Li ◽  
Chunyang Wang ◽  
Yi Zhang ◽  
Owais K Alsrouji ◽  
Alex B Chebl ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Extracellular Vesicles ◽  
Mechanical Thrombectomy ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Therapeutic Effects ◽  
Vessel Occlusion ◽  
Healthy Human ◽  
Stroke Treatment

Treatment of patients with cerebral large vessel occlusion with thrombectomy and tissue plasminogen activator (tPA) leads to incomplete reperfusion. Using rat models of embolic and transient middle cerebral artery occlusion (eMCAO and tMCAO), we investigated the effect on stroke outcomes of small extracellular vesicles (sEVs) derived from rat cerebral endothelial cells (CEC-sEVs) in combination with tPA (CEC-sEVs/tPA) as a treatment of eMCAO and tMCAO in rat. The effect of sEVs derived from clots acquired from patients who had undergone mechanical thrombectomy on healthy human CEC permeability was also evaluated. CEC-sEVs/tPA administered 4 h after eMCAO reduced infarct volume by ∼36%, increased recanalization of the occluded MCA, enhanced cerebral blood flow (CBF), and reduced blood-brain barrier (BBB) leakage. Treatment with CEC-sEVs given upon reperfusion after 2 h tMCAO significantly reduced infarct volume by ∼43%, and neurological outcomes were improved in both CEC-sEVs treated models. CEC-sEVs/tPA reduced a network of microRNAs (miRs) and proteins that mediate thrombosis, coagulation, and inflammation. Patient-clot derived sEVs increased CEC permeability, which was reduced by CEC-sEVs. CEC-sEV mediated suppression of a network of pro-thrombotic, -coagulant, and -inflammatory miRs and proteins likely contribute to therapeutic effects. Thus, CEC-sEVs have a therapeutic effect on acute ischemic stroke by reducing neurovascular damage.

Inflammation as a Therapeutic Target in Acute Ischemic Stroke Treatment

2009 ◽  
Vol 9 (14) ◽  
pp. 1240-1260 ◽  
Author(s):  
Antonino Tuttolomondo ◽  
Riccardo Di Sciacca ◽  
Domenico Di Raimondo ◽  
Chiara Renda ◽  
Antonio Pinto ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Therapeutic Target ◽  
Stroke Treatment

scholarly journals Hypoxia Inducible Factor 1-α in Acute Ischemic Stroke: Good Predictor for Clinical Outcome

2019 ◽  
Author(s):  
Lisda Amalia ◽  
Yeremia Tatang ◽  
Henny Anggraini Sadeli ◽  
Ida Parwati ◽  
Ahmad Rizal ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Small Vessel Disease ◽  
Hypoxia Inducible Factor ◽  
Rank Test ◽  
Large Artery ◽  
Stroke Treatment ◽  
Nihss Score ◽  
Hypoxia Inducible Factor 1 ◽  
Angiogenesis Process

Abstract Background. Stroke is the third leading causes of death and can cause severe disability. Ischemic stroke has a higher prevalence compared to hemorrhage stroke. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor which maintains cellular homeostasis in response to hypoxia. It can trigger apoptosis while stimulating angiogenesis process and decrease neurological deficit after an ischemic stroke. However, this protein complex has not been widely investigated. Objective. Here, we examined the potential of HIF-1α as a marker for neuroplasticity process after ischemic stroke. Methods. Serum HIF-1α were measured in acute ischemic stroke patients. National Institute of Health Stroke Scale (NIHSS) were assessed on the admission and discharge day (between days 7 and 14). To classify the ischemic stroke, we used (Trial of Org 10172 in Acute Stroke Treatment) TOAST criteria. Statistical significances were calculated with Spearman rank test. Results. A total of 58 patients, 31 with large artery atherosclerosis LVD and 27 with small vessel disease (SVD) were included in this study. HIF-1α level in LVD group was (mean ± SD) 0.5225 ± 0.2459 mg/L and in SVD group was 0.3815 ± 0.121 mg/L. HIF-1α was higher (p = 0.004) in LVD group than in SVD group. The initial NIHSS score in LVD group was (mean ± SD) 15.46 ± 2.61 and discharge NIHSS score was 13.31 ± 3.449. Initial NIHSS score in SVD group was 6.07 ± 1.82 and the discharge NIHSS was 5.703 ± 1.7055. In LVD group, HIF-1α was correlated significantly with initial NIHSS (p = 0.0000) and discharge NIHSS (p = 0.0000, r = 0.93). This was also the case for SVD. We found a significant correlation between the level of HIF-1α with initial NIHSS (p = 0.0000) and discharge NIHSS (p = 0.0383) in SVD group (r = 0.94). Conclusion. HIF-1α has a strong correlation with NIHSS and it may be used as the predictor of acute ischemic stroke outcome.

Abstract P201: Octogenarian and Nonagenarian Outcomes Among Acute Ischemic Stroke Patients

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
RAJAN R GADHIA ◽  
Farhaan S Vahidy ◽  
Tariq Nisar ◽  
Destiny Hooper ◽  
David Chiu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Stroke ◽  
Acute Ischemic Stroke ◽  
Combined Treatment ◽  
Stroke Patients ◽  
Stroke Treatment ◽  
Intravenous Tissue Plasminogen Activator ◽  
Significant Difference ◽  
Acute Stroke Treatment ◽  
Iv Tpa

Objective: Most acute stroke treatment trials exclude patients above the age of 80. Given the clear benefit of revascularization with intravenous tissue plasminogen activator (IV tPA) and mechanical thrombectomy (MT), we sought to assess functional outcomes in patients treated above the age of 80. Methods: We conducted a review of all patients admitted to Houston Methodist Hospital between January 2019 and August 2020 with an acute ischemic stroke (AIS) presentation[MOU1] for whom premorbid, discharge, and 90 day modified Rankin Scale scores were available. Patients were categorized by acute stroke treatment (IV tPA, MT, both or none[MOU2] ). mRS values were assessed during admission prior to discharge and at 90 days post stroke event. A delta mRS (Discharge vs. 90-day [MOU3] ) was defined and grouped as no change, improved, or worsened to assess overall functional disability in regards to the index stroke presentation. Results: A total of 865 patients with AIS presentation were included, of whom 651 (75.3%) were <80 years and 214 (24.7%) were > 80 years of age at presentation. A total of 208 patients received IV tPA, 176 underwent revascularization with MT only, 71 had both treatments, and 552 had no acute intervention. In patients >80 yrs who had no acute stroke intervention. mRS improvement was noted in 71.4% compared to 54.1% observed in those patients <80 years. Among patients who received IV tPA, 81.5% of > 80 years improved vs. 61.6% in the younger cohort. A similar trend was noted in the MT and combined treatment groups (76.2% vs. 71.2% and 78.6% vs. 79.3%, respectively). Conclusion: Based on our cohort of acute stroke patients, there was no significant difference in outcomes (as measured by delta mRS) for octogenarians and nonagenarians when compared to younger patients. There was a trend towards improvement in the elderly patients. Chronological age by itself may be an insufficient predictor of functional outcome among stroke patients and age cutoffs for enrollment of patients in acute stroke trials may need additional considerations.

Abstract 215: Differing Perspectives Between Physicians, Patients And Caregivers On The Value Of An Individualized Estimate Of The Benefits Of Thrombolysis At The Time Of Acute Ischemic Stroke: Designing The Resolve (Rapid Evaluation for Stroke Outcomes using Lytics in Vascular Event) Decision Aid

2013 ◽  
Vol 6 (suppl_1) ◽  
Author(s):  
Carole J Decker ◽  
Emily Chhatriwalla ◽  
Brian Garavalia ◽  
John A Spertus ◽  
Er Chen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Qualitative Interviews ◽  
Treatment Decision ◽  
Recombinant Tissue Plasminogen Activator ◽  
Active Role ◽  
Cultural Barriers ◽  
Emergency Physicians ◽  
Stroke Treatment ◽  
Risks And Benefits

Background: Explaining the risks and benefits of recombinant tissue plasminogen activator (rt-PA) occurs in a hurried conversation in the emergency department and may not be fully grasped by patients and their caregivers. Risk models describing the heterogeneity of benefits from rt-PA in acute ischemic stroke (AIS) have been created, but are not used in routine clinical practice. To develop a tool (RESOLVE) for modeling each patient’s benefits and risks for rt-PA, we conducted qualitative interviews with survivors, their caregivers and emergency physicians to inform the design and improve usability. Methods: A multidisciplinary research team conducted qualitative research through 10 focus groups of survivors and caregivers. We obtained feedback on their preferred role, desired information and their impressions of alternative formats for presenting risk and benefits. Three emergency physicians from 2 sites have been interviewed (with >15 additional physician interviews being currently conducted, the results of which will supplement these preliminary data at the time of presentation). Results: Survivors and caregivers (63 participants: 39 stroke survivors; 43% male) express a need for more information, including specific risks and benefits to treatment. In general, both groups desired an active role in the acute stroke treatment decision. In contrast, the initial physician interviews indicated a hesitancy to provide NINDS data to patients and caregivers, skepticism of the existing data and cultural barriers to the use of rt-PA in AIS, the latter acquired through residency training or the opinions of their clinical colleagues. The interviewed clinicians, however, felt more positive about using rt-PA when a neurologist was readily available to support the decision. Conclusions: Preliminary findings suggest reluctance by emergency physicians to share data about the benefits of rt-PA to stroke patients and their caregivers, despite the desire of the latter for such information. While the additional planned interviews will be needed to confirm these findings, preliminary insights suggest a compelling need to overcome the reticence of emergency physicians to use clinical data to better engage patients in making a shared decision about rt-PA in AIS.

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