Low-level blast exposure disrupts gliovascular and neurovascular connections and induces a chronic vascular pathology in rat brain.
Animal model
Blast
Brain
Chronic
Gliovascular
Neurovascular
Rat
Vascular pathology
Journal
Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673
Informations de publication
Date de publication:
09 01 2019
09 01 2019
Historique:
received:
14
11
2018
accepted:
06
12
2018
entrez:
11
1
2019
pubmed:
11
1
2019
medline:
3
4
2020
Statut:
epublish
Résumé
Much concern exists over the role of blast-induced traumatic brain injury (TBI) in the chronic cognitive and mental health problems that develop in veterans and active duty military personnel. The brain vasculature is particularly sensitive to blast injury. The aim of this study was to characterize the evolving molecular and histologic alterations in the neurovascular unit induced by three repetitive low-energy blast exposures (3 × 74.5 kPa) in a rat model mimicking human mild TBI or subclinical blast exposure. High-resolution two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry of purified brain vascular fractions from blast-exposed animals 6 weeks post-exposure showed decreased levels of vascular-associated glial fibrillary acidic protein (GFAP) and several neuronal intermediate filament proteins (α-internexin and the low, middle, and high molecular weight neurofilament subunits). Loss of these proteins suggested that blast exposure disrupts gliovascular and neurovascular interactions. Electron microscopy confirmed blast-induced effects on perivascular astrocytes including swelling and degeneration of astrocytic endfeet in the brain cortical vasculature. Because the astrocyte is a major sensor of neuronal activity and regulator of cerebral blood flow, structural disruption of gliovascular integrity within the neurovascular unit should impair cerebral autoregulation. Disrupted neurovascular connections to pial and parenchymal blood vessels might also affect brain circulation. Blast exposures also induced structural and functional alterations in the arterial smooth muscle layer. Interestingly, by 8 months after blast exposure, GFAP and neuronal intermediate filament expression had recovered to control levels in isolated brain vascular fractions. However, despite this recovery, a widespread vascular pathology was still apparent at 10 months after blast exposure histologically and on micro-computed tomography scanning. Thus, low-level blast exposure disrupts gliovascular and neurovascular connections while inducing a chronic vascular pathology.
Identifiants
pubmed: 30626447
doi: 10.1186/s40478-018-0647-5
pii: 10.1186/s40478-018-0647-5
pmc: PMC6327415
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
6Subventions
Organisme : RRD VA
ID : I01 RX002333
Pays : United States
Organisme : NIMH NIH HHS
ID : R44 MH099721
Pays : United States
Organisme : RRD VA
ID : I01 RX000684
Pays : United States
Organisme : RRD VA
ID : I21 RX002069
Pays : United States
Organisme : RRD VA
ID : I21 RX002876
Pays : United States
Organisme : BLRD VA
ID : I01 BX004067
Pays : United States
Organisme : RRD VA
ID : I01 RX002660
Pays : United States
Organisme : RRD VA
ID : I01 RX000996
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005138
Pays : United States
Références
J Neurotrauma. 2012 Nov 1;29(16):2564-75
pubmed: 22780833
Front Neurol. 2012 Dec 21;3:177
pubmed: 23267342
Neuropharmacology. 2019 Feb;145(Pt B):220-229
pubmed: 30227150
eNeuro. 2018 Jan 30;5(1):
pubmed: 29387781
Magn Reson Imaging. 2012 May;30(4):527-34
pubmed: 22285875
Proc Natl Acad Sci U S A. 2011 Aug 2;108(31):12705-10
pubmed: 21765001
J Neurotrauma. 2011 Jun;28(6):947-59
pubmed: 21449683
Behav Brain Res. 2017 Aug 30;333:43-53
pubmed: 28662892
Rev Physiol Biochem Pharmacol. 1984;101:161-211
pubmed: 6441228
J Neurotrauma. 2011 Oct;28(10):2171-83
pubmed: 21770761
J Trauma. 2010 Oct;69(4):795-804
pubmed: 20215974
Neurol Res. 2014 Nov;36(11):974-82
pubmed: 24730755
Front Neurol. 2011 Apr 04;2:19
pubmed: 21541261
J Vis Exp. 2015 Nov 10;(105):e53208
pubmed: 26574794
Front Neurol. 2015 Jun 12;6:114
pubmed: 26124743
Neuron. 1995 Sep;15(3):711-20
pubmed: 7546749
Neurochem Res. 2014 Sep;39(9):1809-16
pubmed: 25064046
Am J Pathol. 2010 Jan;176(1):353-68
pubmed: 20008141
Acta Neuropathol Commun. 2017 Nov 10;5(1):80
pubmed: 29126430
Biomed Sci Instrum. 2012;48:374-9
pubmed: 22846308
PLoS One. 2015 May 29;10(5):e0127971
pubmed: 26024446
Psychiatr Clin North Am. 2010 Dec;33(4):757-81
pubmed: 21093677
Nature. 2015 Jul 23;523(7561):431-436
pubmed: 26176913
Nature. 2010 Nov 25;468(7323):557-61
pubmed: 20944627
J Neurotrauma. 2017 Feb 15;34(4):952-962
pubmed: 27487732
Sci Transl Med. 2016 Jan 13;8(321):321ra6
pubmed: 26764157
Lancet Neurol. 2016 Aug;15(9):944-953
pubmed: 27291520
J Neurotrauma. 2012 May 1;29(7):1434-54
pubmed: 21639720
J Appl Physiol (1985). 2006 Mar;100(3):1059-64
pubmed: 16467392
J Trauma Acute Care Surg. 2012 Oct;73(4):895-901
pubmed: 22836001
Lancet. 2009 Aug 1;374(9687):405-15
pubmed: 19631372
Acta Neuropathol Commun. 2014 Jun 17;2:67
pubmed: 24938728
Eur J Neurosci. 1994 May 1;6(5):793-804
pubmed: 8075821
J Neurol Sci. 2010 Jul 15;294(1-2):23-8
pubmed: 20478573
J Histochem Cytochem. 1991 Sep;39(9):1267-79
pubmed: 1833448
Curr Neurol Neurosci Rep. 2015 Oct;15(10):68
pubmed: 26299275
Med Hypotheses. 2009 Jan;72(1):76-83
pubmed: 18829180
J Neurosci Res. 2010 Dec;88(16):3530-9
pubmed: 20882564
Front Cell Neurosci. 2014 Dec 10;8:421
pubmed: 25540611
Neurochem Res. 2014 May;39(5):950-60
pubmed: 24682753
Chin J Traumatol. 2015;18(5):267-74
pubmed: 26777709
Free Radic Biol Med. 2013 Jul;60:282-91
pubmed: 23466554
J Neurotrauma. 2018 May 15;35(10):1192-1203
pubmed: 29187028
Front Neurol. 2010 Dec 10;1:151
pubmed: 21206523
J Neurosci Methods. 2016 Oct 15;272:56-68
pubmed: 26861907
Neuroscience. 2016 Apr 5;319:206-20
pubmed: 26777891
Exp Neurol. 2013 Oct;248:520-9
pubmed: 23876514
Cell Tissue Res. 2009 Jan;335(1):5-16
pubmed: 18972135
Behav Brain Res. 2018 Mar 15;340:117-125
pubmed: 27693852
J Trauma. 2006 Oct;61(4):933-42
pubmed: 17033565
Ann Acad Med Singapore. 1997 Jan;26(1):27-9
pubmed: 9140574
Neuron. 2017 Sep 27;96(1):17-42
pubmed: 28957666
Biol Psychiatry. 2013 Apr 1;73(7):613-21
pubmed: 23146357
Sci Rep. 2018 Jul 27;8(1):11344
pubmed: 30054495
Exp Neurol. 2011 Dec;232(2):280-9
pubmed: 21946269
J Neurotrauma. 2011 Jan;28(1):95-104
pubmed: 21083431
J Cereb Blood Flow Metab. 2015 Dec;35(12):1950-6
pubmed: 26104291
J Neurosci Methods. 2007 Jan 30;159(2):277-81
pubmed: 16949675
Front Neurol. 2012 Mar 05;3:32
pubmed: 22403572
Exp Neurol. 2005 Feb;191 Suppl 1:S28-44
pubmed: 15629759
J Neurosci Methods. 2011 Jan 30;195(1):61-6
pubmed: 21129403
J Neurotrauma. 2008 Dec;25(12):1397-406
pubmed: 19146459
Tex Heart Inst J. 2011;38(5):474-85
pubmed: 22163120
Injury. 2019 Jan;50(1):125-130
pubmed: 30219382
J Neurotrauma. 2013 Jul 1;30(13):1147-60
pubmed: 23362798
Mil Med. 2016 May;181(5 Suppl):28-39
pubmed: 27168550
J Neurotrauma. 2013 Jun 1;30(11):958-69
pubmed: 23205671
J Neurotrauma. 2018 Jan 15;35(2):375-392
pubmed: 29160141
Annu Rev Physiol. 2013;75:23-47
pubmed: 23216413
Chin J Traumatol. 2016 Jun 1;19(3):125-8
pubmed: 27321288
N Engl J Med. 2010 Sep 30;363(14):1293-6
pubmed: 20879875
Ann Biomed Eng. 2013 Oct;41(10):2206-14
pubmed: 23568152
J Neurosci Methods. 2007 Jun 15;163(1):76-82
pubmed: 17403541
J Neurotrauma. 2009 Jun;26(6):841-60
pubmed: 19215189
Neurosurgery. 2006 Dec;59(6):1215-25; discussion 1225
pubmed: 17277684
Transl Res. 2015 Dec;166(6):509-528.e1
pubmed: 26414010
Mol Neurobiol. 2015 Dec;52(3):1119-1134
pubmed: 25301233
Front Neurol. 2015 Mar 16;6:48
pubmed: 25852632
J Neurotrauma. 2015 Aug 15;32(16):1200-9
pubmed: 25594545
Transl Stroke Res. 2014 Jun;5(3):385-93
pubmed: 24323722
Cerebrovasc Brain Metab Rev. 1990 Summer;2(2):161-92
pubmed: 2201348
Arch Neurosci. 2017 Apr;4(2):
pubmed: 28758136
Stem Cells. 2007 Jul;25(7):1627-34
pubmed: 17446560
Front Neurol. 2014 Dec 19;5:269
pubmed: 25566175
Acta Neuropathol Commun. 2013 Aug 14;1:51
pubmed: 24252601
Front Neurol. 2016 Oct 18;7:176
pubmed: 27803688
J Neurotrauma. 2014 Jul 15;31(14):1292-304
pubmed: 24673157
PLoS One. 2014 Feb 26;9(2):e89970
pubmed: 24587158
Mol Neurodegener. 2014 Sep 17;9:37
pubmed: 25231386
Sci Transl Med. 2012 May 16;4(134):134ra60
pubmed: 22593173
Sci Rep. 2016 Jun 07;6:26992
pubmed: 27270403
J Cereb Blood Flow Metab. 2011 Dec;31(12):2267-81
pubmed: 21792245
J Neurotrauma. 2011 Oct;28(10):2155-69
pubmed: 21639724