Biomarkers Of Inflammation In Large Vessel Ischemic Stroke (Blis)
Posted Date: Mar 29, 2022
- Investigator: Destiny Hooper
- Specialties: Neurology, Neuroimaging, Stroke
- Type of Study: Observational/Survey
Ischemic stroke, the most common stroke subtype, is an acute vascular emergency that is often clinically devastating. Despite the positive impact of reperfusion-based therapies, ischemic stroke remains the 5th leading cause of death and the leading cause of disability in the United States. Thus, there is a critical need to identify novel therapeutic targets, used alone or as an adjunctive treatment, to expand the therapeutic window and improve outcomes in ischemic stroke. The role of neuroinflammation and its potential as a therapeutic target is actively being investigated in a number of neurologic conditions, including ischemic stroke. The overall premise of BLIS is that ischemic stroke is a multiphasic process in which an initial ischemic phase of neuronal damage is followed by a secondary inflammatory injury, with poorly understood associated mechanisms, that contributes to larger infarct volumes and worse functional outcomes despite successful revascularization. We hypothesize that global transcriptome profiling of miRNA and mRNA collected from intracerebral arterial blood and brain-derived exosomes, will provide much needed insight into the molecular regulation of post-stroke inflammation in humans, in the acute and subacute time frame, and may inform the search for novel treatment strategies for ischemic stroke with large vessel occlusion. Furthermore, given that miRNA activity can be intentionally increased using miRNA mimics or expression vectors, or decreased using inhibitors, identification of specific targets associated with infarct size and long-term outcomes may serve as the basis of future miRNA-based therapeutics. With the greater use of endovascular thrombectomy (EVT) for the treatment of ischemic strokes with large vessel occlusion (LVO), we now have the opportunity to directly sample the molecular milieu within the ischemic vasculature of the human brain. Implementing these techniques, we propose enrolling 16 patients with an acute ischemic stroke with LVO that undergo treatment with EVT and obtaining two arterial blood samples from within the occluded cerebral artery: 1) immediately downstream from the thrombus and 2) just proximal to the thrombus. Successful test collections have already been performed by neurointerventionalist at the University of Cincinnati, without deviation from standard practice or delay in reperfusion. Additionally, a peripheral venous blood sample will be obtained during the procedure, on day-5 and at 90-days. Whole blood transcriptome analysis will be performed using mRNA and microRNA sequencing techniques. Serial imaging will be obtained to calculate infarct growth. Functional outcomes will be assessed at 90 days using the modified Ranken Scale.
Study Inclusion Criteria Includes; 1) Age 18 Years Or Greater, Including Cognitively Impaired Patients 2) Imaging Findings Consistent With A Proximal Anterior Circulation Occlusion (M1 Or Proximal M2 Segment Of Middle Cerebral Artery) 3) Treatment With Endovascular Thrombectomy Within 24 Hours From Last Known Normal At The University Of Cincinnati Hospital 4) Ability Of The Patient Or Legal Representative To Provide Informed Consent 5) Successful Collection Of All Required Samples. Study Exclusion Criteria Includes; 1) Partial/Complete Revascularization With Iv Tpa Prior To Endovascular Thrombectomy 2) Partial/Complete Revascularization During Endovascular Thrombectomy Prior To Post-Thrombus Sample Collection 2) Subocclusive Thrombus 3) Inability To Undergo Mri Brain 4) Known, Recent Systemic Infection Including Covid19 5) Current Status Of Being Incarcerated, In Police Custody, Or Institutionalized.
Ischemic Stroke, Exosome, Inflamation
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Destiny Hooper, Md