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Therapeutic Induction of Collateral Flow

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Abstract

Therapeutic induction of collateral flow as a means to salvage tissue and improve outcome from acute ischemic stroke is a promising approach in the era in which endovascular therapy is no longer time-dependent but collateral-dependent. The importance of collateral flow enhancement as a therapeutic for acute ischemic stroke extends beyond those patients with large amounts of salvageable tissue. It also has the potential to extend the time window for reperfusion therapies in patients who are ineligible for endovascular thrombectomy. In addition, collateral enhancement may be an important adjuvant to neuroprotective agents by providing a more robust vascular route for which treatments can gain access to at risk tissue. However, our understanding of collateral hemodynamics, including under comorbid conditions that are highly prevalent in the stroke population, has hindered the efficacy of collateral flow augmentation for improving stroke outcome in the clinical setting. This review will discuss our current understanding of pial collateral function and hemodynamics, including vasoactivity that is critical for enhancing penumbral perfusion. In addition, mechanisms by which collateral flow can be increased during acute ischemic stroke to limit ischemic injury, that may be different depending on the state of the brain and vasculature prior to stroke, will also be reviewed.

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Fig. 1

Reproduced from Li Z et al., Am J Physiol 2018;315:H1703-H1712

Fig. 2

Reproduced from Chan et al. Stroke 2016;47:1618–1625; Open-access CC BY-NC-ND 4.0 B) Active myogenic vasoconstriction of LMAs and non-LMAs from 18-week-old normotensive WKY rats. *P < 0.05 vs. LMA. C) Myogenic tone of LMA and non-LMAs from 18-week-old WKY rats. *P < 0.05 vs. LMA. Reproduced from Cipolla MJ. Stroke 2021;52:2465–2477

Fig. 3
Fig. 4

Reproduced from Cipolla et al., J Cerebr Blood Flow Metab. 2018;38:755–766. (B) Graph showing % change in collateral flow calculated from filament insertion in normotensive Wistar and hypertensive SHR rats. Collateral flow increased in response to MCAO in Wistar but not SHR. Data will be made available upon reasonable request

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Funding

We are grateful for the continued support of the National Institute of Neurologic Disorders and Stroke grants 2R01NS93289 and R21NS120419.

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  1. Department of Neurological Sciences, University of Vermont Robert Larner College of Medicine, 149 Beaumont Ave, HSRF 416A, Burlington, VT, USA

    Marilyn J. Cipolla

  2. Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Vermont Larner College of Medicine, Burlington, VT, USA

    Marilyn J. Cipolla

  3. Department of Pharmacology, University of Vermont Larner College of Medicine, Burlington, VT, USA

    Marilyn J. Cipolla

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Correspondence to Marilyn J. Cipolla.

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All studies were approved by the Institutional Animal Care and Use committee at the University of Vermont and complied with the National Institutes of Health guidelines for the care and use of laboratory animals.

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Cipolla, M.J. Therapeutic Induction of Collateral Flow. Transl. Stroke Res. 14, 53–65 (2023). https://doi.org/10.1007/s12975-022-01019-2

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