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Acute and Chronic Vascular Responses to Experimental Focal Arterial Stroke in the Neonate Rat

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Abstract

The presence of active developmental angiogenesis and vascular outgrowth in the postnatal brain may differentially affect vascular responses to stroke in newborns and adults, but very little is known about the dynamics of vascular injury and regrowth after stroke during the neonatal period. In this study, we used a clinically relevant animal model of ischemic arterial stroke in neonate rats, a transient middle cerebral artery occlusion (MCAO) in postnatal day 7, to characterize the effects of injury on vascular density and angiogenesis from acute through the chronic phase. A marked vessel degeneration and suppressed endothelial cell proliferation occur in the ischemic regions early after neonatal stroke. In contrast to what has been described in adult animals, endothelial cell proliferation and vascular density are not increased in the peri-ischemic regions during the first week after MCAO in neonates. By 2 weeks after injury, endothelial cell proliferation is increased in the cortical peri-ischemic region, but these changes are not accompanied by an increased vascular density. Suppressed angiogenesis in injured postnatal brain that we report may limit recovery after neonatal stroke. Thus, enhancement of angiogenesis after neonatal stroke may be a promising strategy for the long-term recovery of the affected newborns.

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Acknowledgments

This work was supported by the National Institutes of Health grant RO1 NS44025 (Z.S.V.), National Institutes of Health grant RO1 NS55915 (Z.S.V.), and Postdoctoral Fellowship Program from the Ramón Areces Foundation, Madrid, Spain (D.F.L.). We acknowledge Peter Newman, PhD, Blood Center of Winconsin, for kindly providing anti-PECAM-1 antibody, Erin Oswald, BS, for her support with experiments, and Richard Daneman, PhD, University of California San Francisco, for useful discussions and advice.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Neonatal Brain Disorders Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158-0663, USA

    David Fernández-López, Joel Faustino, Nikita Derugin & Zinaida S. Vexler

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  1. David Fernández-López
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  2. Joel Faustino
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  4. Zinaida S. Vexler
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Correspondence to Zinaida S. Vexler.

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Fernández-López, D., Faustino, J., Derugin, N. et al. Acute and Chronic Vascular Responses to Experimental Focal Arterial Stroke in the Neonate Rat. Transl. Stroke Res. 4, 179–188 (2013). https://doi.org/10.1007/s12975-012-0214-5

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  • DOI: https://doi.org/10.1007/s12975-012-0214-5

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