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Year : 2020  |  Volume : 6  |  Issue : 4  |  Page : 223-224

Beyond reperfusion: Enhancing endogenous restorative functions after an ischemic stroke

Department of Neurosurgery, School of Medicine, Wayne State University, Detroit, MI, USA

Date of Submission12-Dec-2020
Date of Acceptance14-Dec-2020
Date of Web Publication29-Dec-2020

Correspondence Address:
Melissa Wills
Wayne State University School of Medicine, Detroit, Michigan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/bc.bc_72_20

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How to cite this article:
Wills M, Ding Y. Beyond reperfusion: Enhancing endogenous restorative functions after an ischemic stroke. Brain Circ 2020;6:223-4

How to cite this URL:
Wills M, Ding Y. Beyond reperfusion: Enhancing endogenous restorative functions after an ischemic stroke. Brain Circ [serial online] 2020 [cited 2023 May 28];6:223-4. Available from: http://www.braincirculation.org/text.asp?2020/6/4/223/305413

In a mere instant, an ischemic stroke can cause devastating and permanent consequences. The medical community is rife with efforts to prevent stroke, to recognize its ominous signs, and to intervene swiftly. However, endeavors to restore function and to prevent the sequelae of infarction beyond the scope of initial reperfusion are equally vital to a patient's recovery and prognosis. Exercise therapy and ischemic conditioning (IC) are two treatments that lead the vanguard of the long-term rehabilitative strategies.

In “Exercise and Ischemic Conditioning in Stroke Rehabilitation: Part I of a Mini Review on Experimental Concept,” we considered the ways in which exercise therapy stimulates the endogenous processes necessary for recovery from ischemic insults. In vitro, exercise has been shown to promote the expression of proteins involved in angiogenesis, synaptogenesis, and neurogenesis.[1],[2] Unsurprisingly therefore, exercise is recommended for patients in order to both restore various cognitive functions and to minimize the breadth of ischemic damage from stroke. However, many clinical parameters of exercise therapy, such as timing, type of exercise, and feasibility, are yet to be entirely optimized to achieve maximum therapeutic efficacy. By the way of illustration, while early poststroke mobilization is beneficial, doing so within 24 h of infarction has been shown to exacerbate ischemic brain damage through hyperglycolytic and pro-apoptotic mechanisms,[3],[4],[5] and the therapeutic window for safe exercise intervention may only begin 48 h after infarction.[6]

IC, a novel therapy by which patients receive cycles of subcritical ischemia, has been shown to reduce infarct volumes and help patients regain various cognitive and motor skills via similar physiologic mechanisms as exercise.[7],[8] In contrast to exercise therapy, IC's passive nature enables benefit to a potentially broader clinical spectrum of patients, as it is essentially accessible to patients with any level of disability. Its practicality and straightforwardness also invite less uncertainty and more opportunity for standardization in its clinical application. Like its exercise counterpart, the timing of IC is under scrutiny. However, there is no evidence yet to suggest that very early intervention with IC is detrimental or unsafe for the stroke patient – it has even been employed as early as the acute prehospital setting to effectively enhance neuroprotection.[9] Based on the current body of evidence, we find it reasonable to suggest that IC could be used to bridge the temporal gap between the ischemic event and the initiation of exercise therapy, as a dynamic counterpart to exercise therapy, or even as prophylaxis to patients at risk of stroke.

Exercise therapy and IC have been established as catalysts of the body's inherent neuroplastic mechanisms in minimizing the consequences of ischemic stroke. However, supplementary research is needed to refine and standardize these therapeutic regimens, as well as to identify the ways in which their clinical application must be varied to accommodate differences in patient disability, motivation, and stroke subtype. In Part II of this Mini Review, we will explore the clinical outcomes of these highly accessible and affordable therapies and how each one can be optimized.

  References Top

Weng P, Zhang XT, Sheng Q, Tian WF, Chen JL, Yuan JJ, et al. Caveolin-1 scaffolding domain peptides enhance anti-inflammatory effect of heme oxygenase-1 through interrupting its interact with caveolin-1. Oncotarget 2017;8:40104-14.  Back to cited text no. 1
Li F, Geng X, Huber C, Stone C, Ding Y. In search of a dose: The functional and molecular effects of exercise on post-stroke rehabilitation in rats. Front Cell Neurosci 2020;14:186. doi: 10.3389/fncel.2020.00186.  Back to cited text no. 2
Group AT. Efficacy and safety of very early mobilisation within 24 h of stroke onset (AVERT): A randomised controlled trial. Lancet 2015;386:46-55.  Back to cited text no. 3
Shen J, Huber M, Zhao EY, Peng C, Li F, Li X, et al. Early rehabilitation aggravates brain damage after stroke via enhanced activation of nicotinamide adenine dinucleotide phosphate oxidase (NOX). Brain Res 2016;1648:266-76.  Back to cited text no. 4
Li F, Shi W, Zhao EY, Geng X, Li X, Peng C, et al. Enhanced apoptosis from early physical exercise rehabilitation following ischemic stroke. J Neurosci Res 2017;95:1017-24.  Back to cited text no. 5
Tong Y, Cheng Z, Rajah GB, Duan H, Cai L, Zhang N, et al. High intensity physical rehabilitation later than 24 h post stroke is beneficial in patients: A pilot randomized controlled trial (RCT) study in mild to moderate ischemic stroke. Front Neurol 2019;10:113.  Back to cited text no. 6
Doeppner TR, Zechmeister B, Kaltwasser B, Jin F, Zheng X, Majid A, et al. Very delayed remote ischemic post-conditioning induces sustained neurological recovery by mechanisms involving enhanced angioneurogenesis and peripheral immunosuppression reversal. Front Cell Neurosci 2018;12:383.  Back to cited text no. 7
Esposito E, Hayakawa K, Maki T, Arai K, Lo EH. Effects of postconditioning on neurogenesis and angiogenesis during the recovery phase after focal cerebral ischemia. Stroke 2015;46:2691-4. doi: 10.1161/STROKEAHA.115.009070.  Back to cited text no. 8
Purroy F, García C, Mauri G, Pereira C, Torres C, Justes DV, et al. Induced neuroprotection by remote ischemic perconditioning as a new paradigm in ischemic stroke at the acute phase, a systematic review. BMC Neurol 2020;20:266.  Back to cited text no. 9

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