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Article

C-Type Natriuretic Peptide Ameliorates Vascular Injury and Improves Neurological Outcomes in Neonatal Hypoxic-Ischemic Brain Injury in Mice

1
The Lawrence D. Longo, MD Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA
2
Center for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute and Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Anuska V. Andjelkovic
Int. J. Mol. Sci. 2021, 22(16), 8966; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168966
Received: 23 July 2021 / Revised: 10 August 2021 / Accepted: 17 August 2021 / Published: 20 August 2021
(This article belongs to the Special Issue Neuroregeneration and Brain Repair after Stroke)
C-type natriuretic peptide (CNP) is an important vascular regulator that is present in the brain. Our previous study demonstrated the innate neuroprotectant role of CNP in the neonatal brain after hypoxic-ischemic (HI) insults. In this study, we further explored the role of CNP in cerebrovascular pathology using both in vivo and in vitro models. In a neonatal mouse HI brain injury model, we found that intracerebroventricular administration of recombinant CNP dose-dependently reduces brain infarct size. CNP significantly decreases brain edema and immunoglobulin G (IgG) extravasation into the brain tissue, suggesting a vasculoprotective effect of CNP. Moreover, in primary brain microvascular endothelial cells (BMECs), CNP dose-dependently protects BMEC survival and monolayer integrity against oxygen-glucose deprivation (OGD). The vasculoprotective effect of CNP is mediated by its innate receptors NPR2 and NPR3, in that inhibition of either NPR2 or NPR3 counteracts the protective effect of CNP on IgG leakage after HI insult and BMEC survival under OGD. Of importance, CNP significantly ameliorates brain atrophy and improves neurological deficits after HI insults. Altogether, the present study indicates that recombinant CNP exerts vascular protection in neonatal HI brain injury via its innate receptors, suggesting a potential therapeutic target for the treatment of neonatal HI brain injury. View Full-Text
Keywords: hypoxic-ischemic encephalopathy; C-type natriuretic peptide; vascular protection; endothelial cells; NPR2; NPR3 hypoxic-ischemic encephalopathy; C-type natriuretic peptide; vascular protection; endothelial cells; NPR2; NPR3
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MDPI and ACS Style

Shen, G.; Hu, S.; Zhao, Z.; Zhang, L.; Ma, Q. C-Type Natriuretic Peptide Ameliorates Vascular Injury and Improves Neurological Outcomes in Neonatal Hypoxic-Ischemic Brain Injury in Mice. Int. J. Mol. Sci. 2021, 22, 8966. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168966

AMA Style

Shen G, Hu S, Zhao Z, Zhang L, Ma Q. C-Type Natriuretic Peptide Ameliorates Vascular Injury and Improves Neurological Outcomes in Neonatal Hypoxic-Ischemic Brain Injury in Mice. International Journal of Molecular Sciences. 2021; 22(16):8966. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168966

Chicago/Turabian Style

Shen, Guofang, Shirley Hu, Zhen Zhao, Lubo Zhang, and Qingyi Ma. 2021. "C-Type Natriuretic Peptide Ameliorates Vascular Injury and Improves Neurological Outcomes in Neonatal Hypoxic-Ischemic Brain Injury in Mice" International Journal of Molecular Sciences 22, no. 16: 8966. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168966

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