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 ◽  
...  
2021 ◽  
pp. 0271678X2199298
Author(s):  
Chao Li ◽  
Chunyang Wang ◽  
Yi Zhang ◽  
Owais K Alsrouji ◽  
Alex B Chebl ◽  
...  

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.


2019 ◽  
Author(s):  
Lisda Amalia ◽  
Yeremia Tatang ◽  
Henny Anggraini Sadeli ◽  
Ida Parwati ◽  
Ahmad Rizal ◽  
...  

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.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
RAJAN R GADHIA ◽  
Farhaan S Vahidy ◽  
Tariq Nisar ◽  
Destiny Hooper ◽  
David Chiu ◽  
...  

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.


Author(s):  
Carole J Decker ◽  
Emily Chhatriwalla ◽  
Brian Garavalia ◽  
John A Spertus ◽  
Er Chen ◽  
...  

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.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Janhavi M Modak ◽  
Syed Daniyal Asad ◽  
Jussie Lima ◽  
Amre Nouh ◽  
Ilene Staff ◽  
...  

Introduction: Acute ischemic stroke treatment has undergone a paradigm shift, with patients being treated in the extended time window (6-24 hours post symptom onset). The purpose of this study is to assess outcomes in stroke patients above 80 years of age undergoing endovascular treatment (EVT) in the extended time window. Methods: Acute ischemic stroke patients presenting to Hartford Hospital between January 2017 to June 2019 were considered for the study. Stroke outcomes in patients above 80 years of age with anterior circulation ischemic strokes presenting in the extended time window (Group A, n=30) were compared to a younger cohort of patients below 80 years (Group B, n=31). Patients over 80 years treated in the traditional time window (within 6 hours of symptom onset) served as a second set of controls (Group C, n=40). Statistical analysis was performed with a significance level of 0.05 Results: For angiographic results, there were no statistically significant differences in terms of good outcomes (TICI 2b-3) among patients of Group A, when compared to Groups B or C (p>0.05). For the endovascular procedures, no significant differences were noted in the total fluoroscopy time (Median Group A 44.05, Group B 38.1, Group C 35.25 min), total intra-procedure time (Median Group A 144, Group B 143, Group C 126 min) or total radiation exposure (Median Group A 8308, Group B 8960, Group C 8318 uGy-m 2 ). For stroke outcomes, a good clinical outcome was defined as modified Rankin score of 0-2 at discharge. Significantly better outcomes were noted in the younger patients in Group B - 35.4%, when compared to 13.3% in Group A (p=0.03). Comparative outcomes differed in the elderly patients above 80 years, Group A -13.3% vs Group C - 25%, although not statistically significant (p=0.23). There was a significant difference in mortality in patients of Group A - 40% as compared to 12% in the younger cohort, Group B (p= 0.01). Conclusions: In the extended time window, patients above 80 years of age were noted to have a higher mortality, morbidity compared to the younger cohort of patients. No significant differences were noted in the stroke outcomes in patients above 80 years of age when comparing the traditional and the extended time window for stroke treatment.


Stroke ◽  
2018 ◽  
Vol 49 (Suppl_1) ◽  
Author(s):  
Vasu Saini ◽  
Fadar O Otite ◽  
Priyank Khandelwal ◽  
Dileep R Yavagal ◽  
Seemant Chaturvedi ◽  
...  

Neurosurgery ◽  
2019 ◽  
Vol 85 (suppl_1) ◽  
pp. S47-S51
Author(s):  
Kimberly P Kicielinski ◽  
Christopher S Ogilvy

Abstract As ischemic stroke care advances with more patients eligible for mechanical thrombectomy, so too does the role of the neurosurgeon in these patients. Neurosurgeons are an important member of the team from triage through the intensive care unit. This paper explores current research and insights on the contributions of neurosurgeons in care of acute ischemic stroke patients in the acute setting.


2015 ◽  
Vol 8 (6) ◽  
pp. 568-570 ◽  
Author(s):  
Veer A Shah ◽  
Coleman O Martin ◽  
Angela M Hawkins ◽  
William E Holloway ◽  
Shilpa Junna ◽  
...  

BackgroundThe increasing utilization of balloon guide catheters (BGCs) in thrombectomy therapy for ischemic stroke has led to concerns about large-bore sheaths causing vascular groin complications.Objective To retrospectively assess the impact of large large-bore sheaths and vascular closure devices on groin complication rates at a comprehensive stroke center over a 10-year period.MethodsRadiological and clinical records of patients with acute ischemic stroke who underwent mechanical endovascular therapy with an 8Fr or larger sheaths were reviewed. A groin complication was defined as the formation of a groin hematoma, retroperitoneal hematoma, femoral artery pseudoaneurysm, or the need for surgical repair. Information collected included size of sheath, type of hemostatic device, and anticoagulation status of the patient. Blood bank records were also analyzed to identify patients who may have had an undocumented blood transfusion for a groin hematoma.ResultsA total of 472 patients with acute ischemic stroke who underwent mechanical thrombectomy with a sheath and BGC sized 8Fr or larger were identified. 260 patients (55.1%) had tissue Plasminogen Activator (tPA) administered as part of stroke treatment. Vascular closure devices were used in 97.9% of cases (n=462). Two patients were identified who had definite groin complications and a further two were included as having possible complications. There was a very low rate of clinically significant groin complications (0.4–0.8%) associated with the use of large-bore sheaths.ConclusionsThese findings suggest that concerns for groin complications should not preclude the use of BGCs and large-bore sheaths in mechanical thrombectomy for acute ischemic stroke.


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