Angiopoietin/Tie2 Axis Regulates the Age-at-Injury Cerebrovascular Response to Traumatic Brain Injury

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Thomas R BricklerMichelle H Theus

Abstract

Although age-at-injury influences chronic recovery from traumatic brain injury (TBI), the differential effects of age on early outcome remain understudied. Using a male murine model of moderate contusion injury, we investigated the underlying mechanism(s) regulating the distinct response between juvenile and adult TBI. We demonstrate similar biomechanical and physical properties of naive juvenile and adult brains. However, following controlled cortical impact (CCI), juvenile mice displayed reduced cortical lesion formation, cell death, and behavioral deficits at 4 and 14 d. Analysis of high-resolution laser Doppler imaging showed a similar loss of cerebral blood flow (CBF) in the ipsilateral cortex at 3 and 24 h post-CCI, whereas juvenile mice showed enhanced subsequent restoration at 2-4 d compared with adults. These findings correlated with reduced blood-brain barrier (BBB) disruption and increased perilesional vessel density. To address whether an age-dependent endothelial cell (EC) response affects vessel stability and tissue outcome, we magnetically isolated CD31+ ECs from sham and injured cortices and evaluated mRNA expression. Interestingly, we found increased transcripts for BBB stability-related genes and reduced expre...Continue Reading

Citations

Nov 7, 2019·The Journal of Clinical Investigation·Benjamin OkyereMichelle H Theus
Apr 16, 2020·Cell Communication and Signaling : CCS·Yunxiang ZhouJianmin Zhang
Feb 1, 2019·International Journal of Molecular Sciences·Shotaro Michinaga, Yutaka Koyama
Nov 13, 2019·Journal of Neuroinflammation·Elizabeth A KowalskiMichelle H Theus
Jan 31, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Neel S SinghalDengke K Ma
May 14, 2020·International Journal of Molecular Sciences·Alison Cash, Michelle H Theus
Jan 5, 2021·Frontiers in Immunology·Juliane GustCameron J Turtle
Apr 10, 2021·Proceedings of the National Academy of Sciences of the United States of America·Jingling LiSundari Chetty
Nov 18, 2020·The Journal of Head Trauma Rehabilitation·Amy A HerroldTheresa L Bender Pape
Jul 24, 2021·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Deirdre A KillebrewRick B Meeker
Oct 27, 2021·EMBO Reports·Yan Ting ZhaoHannele Ruohola-Baker

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