Document Type
Article
Publication Date
7-15-2023
Original Citation
Sadanandan J,
Sathyanesan M,
Liu Y,
Tiwari N,
Newton S.
Carbamoylated Erythropoietin-Induced Cerebral Blood Perfusion and Vascular Gene Regulation. Int J Mol Sci. 2023;24(14).
Keywords
JCA, Humans, Endothelial Cells, Erythropoietin, Epoetin Alfa, Gene Expression Regulation, Perfusion
JAX Source
Int J Mol Sci. 2023;24(14).
ISSN
1422-0067
PMID
37511274
DOI
https://doi.org/10.3390/ijms241411507
Grant
This work was supported by U.S. Public Health Service (National Institutes of Health) grants, MH106640 and 3P20GM103443-20S1 (S.S.N.), and the University of South Dakota Center for Brain and Behavioral Research.
Abstract
Cerebral hypoperfusion is associated with enhanced cognitive decline and increased risk of neuropsychiatric disorders. Erythropoietin (EPO) is a neurotrophic factor known to improve cognitive function in preclinical and clinical studies of neurodegenerative and psychiatric disorders. However, the clinical application of EPO is limited due to its erythropoietic activity that can adversely elevate hematocrit in non-anemic populations. Carbamoylated erythropoietin (CEPO), a chemically engineered non-erythropoietic derivative of EPO, does not alter hematocrit and maintains neurotrophic and behavioral effects comparable to EPO. Our study aimed to investigate the role of CEPO in cerebral hemodynamics. Magnetic resonance imaging (MRI) analysis indicated increased blood perfusion in the hippocampal and striatal region without altering tight junction integrity. In vitro and in vivo analyses indicated that hippocampal neurotransmission was unaltered and increased cerebral perfusion was likely due to EDRF, CGRP, and NOS-mediated vasodilation. In vitro analysis using human umbilical vein endothelial cells (HUVEC) and hippocampal vascular gene expression analysis showed CEPO to be a non-angiogenic agent which regulates the MEOX2 gene expression. The results from our study demonstrate a novel role of CEPO in modulating cerebral vasodilation and blood perfusion.
Comments
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).