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

Authors

Guofang Shen, The Lawrence D. Longo, MD Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Shirley Hu, The Lawrence D. Longo, MD Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.Follow
Zhen Zhao, 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.
Lubo Zhang, The Lawrence D. Longo, MD Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.Follow
Qingyi Ma, The Lawrence D. Longo, MD Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.Follow

Document Type

Article

Publication Date

8-20-2021

Publication Title

International journal of molecular sciences

E-ISSN

1422-0067

Abstract

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.

Volume

22

Issue

16

DOI

10.3390/ijms22168966

PubMed ID

34445671

Recommended Citation

Shen, Guofang; Hu, Shirley; Zhao, Zhen; Zhang, Lubo; and Ma, Qingyi, "C-Type Natriuretic Peptide Ameliorates Vascular Injury and Improves Neurological Outcomes in Neonatal Hypoxic-Ischemic Brain Injury in Mice" (2021). Loma Linda University Faculty Publications. 323.
https://scholarsrepository.llu.edu/fac_pubs/323