basic sciences

Melissa Trotman-Lucas, PhD, BSc
@TroLucaM

Thakkar P, McGregor A, Barber PA, Paton JFR, Barrett C, McBryde F. Hypertensive Response to Ischemic Stroke in the Normotensive Wistar Rat: Mechanisms and Therapeutic Relevance. Stroke. 2019;50:2522-2530.

Sudden increased blood pressure (BP), known as hypertension, following an ischaemic insult is the scenario for ~80% of acute ischaemic stroke (AIS) patients. This poststroke hypertension is the subject of continued scientific debate, with both the mechanism and its therapeutic relevance still poorly understood. There are two potential sides to the role of poststroke hypertension in AIS tissue damage: exacerbation and protection. Exacerbation of damage to vulnerable ischemic tissue may occur alongside promotion of edema formation; moreover, this abrupt increase in BP can increase the risk of cardiovascular events, including further strokes and heart attacks. On the flip side, this increased BP may be a reaction by the body to increase blood supply to the brain tissue, increasing oxygenation of the penumbral tissue. Therefore, creating the conundrum that treatment to reduce BP levels in AIS may be protective but, on the other hand, it may also escalate tissue damage and increase the risk of a poorer patient outcome.

A recent study by Thakkar et al., published in Stroke, sought to answer whether a neurally mediated increase in systemic BP protects cerebral perfusion by opposing the increase in intracranial pressure (ICP) through increasing supply pressure to the tissues. Undertaking this by characterising the cerebrovascular, ICP and cerebral oxygenation responses in a rat AIS model. Testing also the physiological impact of hypertension prevention on the maintenance of oxygenation in the penumbra and on functional recovery poststroke.

Lin Kooi Ong, PhD
@DrLinOng

Perego C, Fumagalli S, Miteva K, Kallikourdis M, De Simoni M-G. Combined Genetic Deletion of IL (Interleukin)-4, IL-5, IL-9, and IL-13 Does Not Affect Ischemic Brain Injury in Mice. Stroke. 2019;50:2207–2215

Primary brain injury occurs immediately after the onset of stroke, and triggers a cascade of immune responses including glial activation, recruitment of peripheral immune cells and release of cytokines and chemokines. These inflammation responses may aggravate brain injury by enhancing oxidative stress, production of neurotoxic proteins and disruption of neurovascular unit. On the other hand, inflammation may also participate in waste clearance, production of neurotropic factors and support the survivor of neurons. The recognition of the crucial role of inflammation after stroke has motivated stroke researchers to investigate novel interventions to target brain inflammation processes, leading to improve neurological outcome.

Victor J. Del Brutto, MD

Bieber M, Schuhmann MK, Volz J, Kumar GJ, Vaidya JR, Nieswandt, et al. Description of a Novel Phosphodiesterase (PDE)-3 Inhibitor Protecting Mice From Ischemic Stroke Independent From Platelet Function. Stroke. 2018;50:478–486.

Inhibition of phosphodiesterase-3 (PDE-3) in platelets increases intracellular cAMP levels resulting in blockage of platelet aggregation induced by collagen, adenosine diphosphate, arachidonic acid, and epinephrine. In addition, PDE-3 inhibitors have a pleiotropic effect over blood vessels, which include arteriolar vasodilation, endothelial repair, smooth muscle anti-proliferative effect, and reduction of endothelial inflammatory response.

Although considered to have a central antiplatelet mechanism of action, PDE-3 inhibitors exert its vascular protective effect through the diverse therapeutic targets listed above. Cilostazol, a PDE-3 inhibitor prototype, is often used chronically in patients with peripheral vascular disease, as well as for coronary artery disease and stroke secondary prevention, particularly in Asian countries. There is growing evidence on the long-term efficacy and safety of cilostazol used among patients with non-cardioembolic stroke, especially when used in combination with aspirin or clopidogrel. However, little is known about its neuroprotective effects during acute ischemic injury.

Kate Hayward, PhD, PT
@kate_hayward_

Jeffers MS, Corbett D. Synergistic Effects of Enriched Environment and Task-Specific Reach Training on Poststroke Recovery of Motor Function. Stroke. 2018

Studies have previously demonstrated the efficacy of environmental enrichment and task-specific training to promote post-stroke recovery. The premise is that enrichment creates a neuroplastic milieu that is permissive for recovery, and task-specific training capitalizes on this environment to induce neuroplastic changes and promote motor recovery. Despite the efficacy of this synergistic approach, the respective contribution of each of these components had not been directly compared until this paper by Jeffers and Corbett (1).

This study demonstrated that the combination of environmental enrichment plus task-specific reach training (environment+reach) resulted in significant improvements in reaching (single-pellet retrieval) at both 4- and 9- weeks post-stroke compared to reach training alone or enrichment alone. Further, the enrichment+reach group was the only group that did not differ significantly from the sham group (no stroke) at 4- and 9-weeks post stroke. This indicates significant functional recovery had occurred; all groups were significantly impaired compared to sham at initial post-stroke assessment.