Nitric oxide synthase mediates cerebellar dysfunction in mice exposed to repetitive blast-induced mild traumatic brain injury.

Scientific Reports
Aric F LogsdonD G Cook

Abstract

We investigated the role of nitric oxide synthase (NOS) in mediating blood-brain barrier (BBB) disruption and peripheral immune cell infiltration in the cerebellum following blast exposure. Repetitive, but not single blast exposure, induced delayed-onset BBB disruption (72 hours post-blast) in cerebellum. The NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) administered after blast blocked BBB disruption and prevented CD4+ T-cell infiltration into cerebellum. L-NAME also blocked blast-induced increases in intercellular adhesion molecule-1 (ICAM-1), a molecule that plays a critical role in regulating blood-to-brain immune cell trafficking. Blocking NOS-mediated BBB dysfunction during this acute/subacute post-blast interval (24-71 hours after the last blast) also prevented sensorimotor impairment on a rotarod task 30 days later, long after L-NAME cleared the body. In postmortem brains from Veterans/military Servicemembers with blast-related TBI, we found marked Purkinje cell dendritic arbor structural abnormalities, which were comparable to neuropathologic findings in the blast-exposed mice. Taken collectively, these results indicate that blast provokes delayed-onset of NOS-dependent pathogenic cascades that can later em...Continue Reading

References

Jun 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·P KubesD N Granger
Nov 1, 1970·The American Journal of Physiology·V A LevinC S Patlak
Mar 1, 1983·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·C S PatlakJ D Fenstermacher
Mar 1, 1983·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·R G BlasbergC S Patlak
May 1, 1994·Journal of Neuroimmunology·B EngelhardtE C Butcher
Jul 1, 1995·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·S Rahner-WelschW Kuschinsky
Sep 1, 1996·Journal of Neurosurgery·S A BaldwinS W Scheff
May 1, 1996·Journal of Neurotrauma·K FukudaL J Noble
Dec 22, 1998·European Journal of Clinical Pharmacology·J A AvontuurH A Bruining
Jun 22, 2002·Annals of the New York Academy of Sciences·Ahmad KhaldiJ J Woodward
Nov 1, 2002·Acta Neuropathologica·Hiroko NonakaFumie Ihara
Jul 1, 2005·Neurosurgery·Bennet I OmaluCyril H Wecht
May 6, 2006·The Journal of Physiology·Takuya HatakeyamaWalter N Durán
Apr 4, 2009·Physiological Reviews·Carmen Ruiz de AlmodovarPeter Carmeliet
May 20, 2009·Journal of Biomechanical Engineering·Paul A Taylor, Corey C Ford
May 22, 2009·NeuroImage·Deborah L WardenDavid F Moore
Jun 6, 2009·The Cerebellum·Matthew B PottsLinda J Noble-Haeusslein
Sep 24, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Oliver SteinerRuth Lyck
Mar 5, 2011·The Cerebellum·Catherine J Stoodley
Apr 1, 2011·Journal of Neurotrauma·Robert H GarmanPatrick M Kochanek
Apr 14, 2011·Journal of Neuropathology and Experimental Neurology·Vassilis E KoliatsosDeidre Lee
Jun 3, 2011·The New England Journal of Medicine·Christine L Mac DonaldDavid L Brody
May 18, 2012·Science Translational Medicine·Lee E GoldsteinAnn C McKee
Dec 6, 2012·The American Journal of Psychiatry·Ricardo E JorgeVincent A Magnotta
Apr 10, 2013·Annals of Biomedical Engineering·Stewart YeohKenneth L Monson
Sep 3, 2013·The Cerebellum·Leonard F KoziolTadashi Yamazaki

❮ Previous
Next ❯

Citations

Aug 8, 2020·Journal of the Neurological Sciences·James S MeabonElaine R Peskind
Jan 9, 2022·Scientific Reports·Robin BishopRaymond A Swanson

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
confocal microscopy
electrophoresis

Clinical Trials Mentioned

NCT03260569

Software Mentioned

SPSS
GraphPad Prism
FlowJo
Leica Application Suite
GraphPad
Image
Quant
ARRIVE

Related Concepts

Related Feeds

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Blood Brain Barrier Regulation in Health & Disease

The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Brain Injury & Trauma

brain injury after impact to the head is due to both immediate mechanical effects and delayed responses of neural tissues.