PRMT7 Can Prevent Neurovascular Uncoupling, Blood-Brain Barrier Permeability, and Mitochondrial Dysfunction in Repetitive and Mild Traumatic Brain Injury

Authors

Christina H Acosta
Garrett A Clemons
Cristiane T Citadin
William C Carr
Mariana Sayuri Berto Udo
Vesna Tesic
Henry W Sanicola
Anne H Freelin
Jamie B Toms
J Dedrick Jordan
Bharat Guthikonda
Krista M Rodgers
Celeste Yin-Chieh Wu
Reggie Hui-Chao Lee
Hung Wen Lin

Publication Date

8-1-2023

Journal

Experimental Neurology

DOI

10.1016/j.expneurol.2023.114445

PMID

37196697

PMCID

PMC10960645

PubMedCentral® Posted Date

March 2024

PubMedCentral® Full Text Version

Author MSS

Abstract

Mild traumatic brain injury (TBI) comprises the largest percentage of TBI-related injuries, with pathophysiological and functional deficits that persist in a subset of TBI patients. In our three-hit paradigm of repetitive and mild traumatic brain injury (rmTBI), we observed neurovascular uncoupling via decreased red blood cell velocity, microvessel diameter, and leukocyte rolling velocity 3 days post-rmTBI via intra-vital two-photon laser scanning microscopy. Furthermore, our data suggest increased blood-brain barrier (BBB) permeability (leakage), with corresponding decrease in junctional protein expression post-rmTBI. Mitochondrial oxygen consumption rates (measured via Seahorse XFe24) were also altered 3 days post-rmTBI, along with disrupted mitochondrial dynamics of fission and fusion. Overall, these pathophysiological findings correlated with decreased protein arginine methyltransferase 7 (PRMT7) protein levels and activity post-rmTBI. Here, we increased PRMT7 levels in vivo to assess the role of the neurovasculature and mitochondria post-rmTBI. In vivo overexpression of PRMT7 using a neuronal specific AAV vector led to restoration of neurovascular coupling, prevented BBB leakage, and promoted mitochondrial respiration, altogether to suggest a protective and functional role of PRMT7 in rmTBI.

Keywords

Humans, Brain Concussion, Blood-Brain Barrier, Brain Injuries, Traumatic, Respiration, Protein-Arginine N-Methyltransferases

Published Open-Access

yes

Recommended Citation

Acosta, Christina H; Clemons, Garrett A; Citadin, Cristiane T; et al., "PRMT7 Can Prevent Neurovascular Uncoupling, Blood-Brain Barrier Permeability, and Mitochondrial Dysfunction in Repetitive and Mild Traumatic Brain Injury" (2023). Faculty, Staff and Student Publications. 1520.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/1520