the-stroke-preclinical-assessment-network-multi-laboratory-model

The Stroke Preclinical Assessment Network Multi-Laboratory Model of Thromboembolic Stroke with Thrombolysis: TE-MCAo

Current translational rodent stroke models induce middle cerebral artery occlusion (MCAo) using nylon filaments, injected emboli, intraluminal thrombin, ...

The Medical College of Georgia at Augusta University

Multipotent adult progenitor cells are a bone marrow-derived, allogeneic, cell therapy product that modulates the immune system, and represents a promising therapy for acute stroke. We aimed to identify the highest, well-tolerated, and safest single dose of multipotent adult progenitor cells, and if they were efficacious as a treatment for stroke recovery.

Safety and efficacy of multipotent adult progenitor cells in acute ischaemic stroke (MASTERS): a randomised, double-blind, placebo-controlled, phase 2 trial.

Vascular contributions to cognitive impairment and dementia (VCID) make up 50% of the cases of dementia. The purpose of this study was to determine the effect of chronic remote ischemic conditioning (C-RIC) on improving long-term (6 months) outcomes and cerebral blood flow (CBF) and collateral formation in a mouse model of VCID. Adult C57BL/6J male mice (10 weeks) were randomly assigned to four different groups: (1) sham-bilateral carotid artery stenosis (BCAS), (2) BCAS + sham RIC, (3) BCAS+C-RIC for 1 month (1MO), and (4) BCAS+C-RIC-4 months (4MO). CBF, cognitive impairment, and functional outcomes were performed up for 6 months after BCAS surgery. The expression of CD31, α-SMA, and myelin basic protein (MBP) was assessed by immunohistochemistry (IHC). Additional set of mice were randomized to sham, BCAS, and BCAS+C-RIC. The cerebrovascular angioarchitecture was studied with micro-CT. RIC therapy for either 1 or 4 months significantly improved CBF, new collateral formation, functional and cognitive outcomes, and prevented white matter damage. There was no difference between C-RIC for 1 or 4 months; IHC studies at 6 months showed an increase in brain CD31 and α-SMA expression indicating increased angiogenesis and MBP indicating preservation of white matter in animals receiving RIC. One month of daily RIC is as effective as 4 months of daily RIC in improving CBF, angiogenesis, and long-term functional outcomes (6 months) in a VCID model. This suggests that 1 month of RIC is sufficient to reduce cognitive impairment and induce beneficial cerebrovascular remodeling.

Chronic Remote Ischemic Conditioning Is Cerebroprotective and Induces Vascular Remodeling in a VCID Model.

The purpose of this article is to provide a review of state-of-the-art cellular therapy in cerebrovascular diseases by discussing published and ongoing clinical trials.

Stem Cell Therapy in Cerebrovascular Disease.

The COVID-19 pandemic is associated with neurological symptoms and complications including stroke. There is hypercoagulability associated with COVID-19 that is likely a "sepsis-induced coagulopathy" and may predispose to stroke. The SARS-CoV-2 virus binds to angiotensin-converting enzyme 2 (ACE2) present on brain endothelial and smooth muscle cells. ACE2 is a key part of the renin angiotensin system (RAS) and a counterbalance to angiotensin-converting enzyme 1 (ACE1) and angiotensin II. Angiotensin II is proinflammatory, is vasoconstrictive, and promotes organ damage. Depletion of ACE2 by SARS-CoV-2 may tip the balance in favor of the "harmful" ACE1/angiotensin II axis and promote tissue injury including stroke. There is a rationale to continue to treat with tissue plasminogen activator for COVID-19-related stroke and low molecular weight heparinoids may reduce thrombosis and mortality in sepsis-induced coagulopathy.

COVID-19-Related Stroke.

A large number of basic and clinical studies have demonstrated that remote ischaemic conditioning (RIC) has neuroprotective effects. Recently, RIC has made gratifying progress in the field of ischaemia stroke treatment. A considerable number of basic and clinical studies have also revealed the possible therapeutic effects of RIC on subarachnoid haemorrhage. However, the neuroprotective effect of RIC on subarachnoid haemorrhage is still lacking convincing evidence and deserves further study.

Remote ischaemic conditioning for efficacy in patients with aneurysmal subarachnoid haemorrhage (REPAIR): protocol for a multicentre, randomised, double-blind, sham-controlled, parallel-group trial.

Article	Year
Safety and efficacy of multipotent adult progenitor cells in acute ischaemic stroke (MASTERS): a randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet. Neurology\| PubMed ID: 28320635	2017
Chronic Remote Ischemic Conditioning Is Cerebroprotective and Induces Vascular Remodeling in a VCID Model. Translational stroke research\| PubMed ID: 28755277	2018
Stem Cell Therapy in Cerebrovascular Disease. Current treatment options in neurology\| PubMed ID: 30298218	2018
COVID-19-Related Stroke. Translational stroke research\| PubMed ID: 32378030	2020
Remote ischaemic conditioning for efficacy in patients with aneurysmal subarachnoid haemorrhage (REPAIR): protocol for a multicentre, randomised, double-blind, sham-controlled, parallel-grou... BMJ open\| PubMed ID: 40789732	2025

David C Hess

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