Blood–brain barrier disruption and ventricular enlargement are the earliest neuropathological changes in rats with repeated sub-concussive impacts over 2 weeks

Abstract Repeated sub-concussive impact (e.g. soccer ball heading), a significantly lighter form of mild traumatic brain injury, is increasingly suggested to cumulatively alter brain structure and compromise neurobehavioural function in the long-term. However, the underlying mechanisms whereby repea...

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Autores principales:	Bailey Hiles-Murison, Andrew P. Lavender, Mark J. Hackett, Joshua J. Armstrong, Michael Nesbit, Samuel Rawlings, Terrence McGonigle, Andrew Warnock, Virginie Lam, John C. L. Mamo, Melinda Fitzgerald, Ryu Takechi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cf82d2fd2ba345389667629116ebde2a
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spelling	oai:doaj.org-article:cf82d2fd2ba345389667629116ebde2a2021-12-02T17:20:12ZBlood–brain barrier disruption and ventricular enlargement are the earliest neuropathological changes in rats with repeated sub-concussive impacts over 2 weeks10.1038/s41598-021-88854-92045-2322https://doaj.org/article/cf82d2fd2ba345389667629116ebde2a2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88854-9https://doaj.org/toc/2045-2322Abstract Repeated sub-concussive impact (e.g. soccer ball heading), a significantly lighter form of mild traumatic brain injury, is increasingly suggested to cumulatively alter brain structure and compromise neurobehavioural function in the long-term. However, the underlying mechanisms whereby repeated long-term sub-concussion induces cerebral structural and neurobehavioural changes are currently unknown. Here, we utilised an established rat model to investigate the effects of repeated sub-concussion on size of lateral ventricles, cerebrovascular blood–brain barrier (BBB) integrity, neuroinflammation, oxidative stress, and biochemical distribution. Following repeated sub-concussion 3 days per week for 2 weeks, the rats showed significantly enlarged lateral ventricles compared with the rats receiving sham-only procedure. The sub-concussive rats also presented significant BBB dysfunction in the cerebral cortex and hippocampal formation, whilst neuromotor function assessed by beamwalk and rotarod tests were comparable to the sham rats. Immunofluorescent and spectroscopic microscopy analyses revealed no significant changes in neuroinflammation, oxidative stress, lipid distribution or protein aggregation, within the hippocampus and cortex. These data collectively indicate that repeated sub-concussion for 2 weeks induce significant ventriculomegaly and BBB disruption, preceding neuromotor deficits.Bailey Hiles-MurisonAndrew P. LavenderMark J. HackettJoshua J. ArmstrongMichael NesbitSamuel RawlingsTerrence McGonigleAndrew WarnockVirginie LamJohn C. L. MamoMelinda FitzgeraldRyu TakechiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bailey Hiles-Murison Andrew P. Lavender Mark J. Hackett Joshua J. Armstrong Michael Nesbit Samuel Rawlings Terrence McGonigle Andrew Warnock Virginie Lam John C. L. Mamo Melinda Fitzgerald Ryu Takechi Blood–brain barrier disruption and ventricular enlargement are the earliest neuropathological changes in rats with repeated sub-concussive impacts over 2 weeks
description	Abstract Repeated sub-concussive impact (e.g. soccer ball heading), a significantly lighter form of mild traumatic brain injury, is increasingly suggested to cumulatively alter brain structure and compromise neurobehavioural function in the long-term. However, the underlying mechanisms whereby repeated long-term sub-concussion induces cerebral structural and neurobehavioural changes are currently unknown. Here, we utilised an established rat model to investigate the effects of repeated sub-concussion on size of lateral ventricles, cerebrovascular blood–brain barrier (BBB) integrity, neuroinflammation, oxidative stress, and biochemical distribution. Following repeated sub-concussion 3 days per week for 2 weeks, the rats showed significantly enlarged lateral ventricles compared with the rats receiving sham-only procedure. The sub-concussive rats also presented significant BBB dysfunction in the cerebral cortex and hippocampal formation, whilst neuromotor function assessed by beamwalk and rotarod tests were comparable to the sham rats. Immunofluorescent and spectroscopic microscopy analyses revealed no significant changes in neuroinflammation, oxidative stress, lipid distribution or protein aggregation, within the hippocampus and cortex. These data collectively indicate that repeated sub-concussion for 2 weeks induce significant ventriculomegaly and BBB disruption, preceding neuromotor deficits.
format	article
author	Bailey Hiles-Murison Andrew P. Lavender Mark J. Hackett Joshua J. Armstrong Michael Nesbit Samuel Rawlings Terrence McGonigle Andrew Warnock Virginie Lam John C. L. Mamo Melinda Fitzgerald Ryu Takechi
author_facet	Bailey Hiles-Murison Andrew P. Lavender Mark J. Hackett Joshua J. Armstrong Michael Nesbit Samuel Rawlings Terrence McGonigle Andrew Warnock Virginie Lam John C. L. Mamo Melinda Fitzgerald Ryu Takechi
author_sort	Bailey Hiles-Murison
title	Blood–brain barrier disruption and ventricular enlargement are the earliest neuropathological changes in rats with repeated sub-concussive impacts over 2 weeks
title_short	Blood–brain barrier disruption and ventricular enlargement are the earliest neuropathological changes in rats with repeated sub-concussive impacts over 2 weeks
title_full	Blood–brain barrier disruption and ventricular enlargement are the earliest neuropathological changes in rats with repeated sub-concussive impacts over 2 weeks
title_fullStr	Blood–brain barrier disruption and ventricular enlargement are the earliest neuropathological changes in rats with repeated sub-concussive impacts over 2 weeks
title_full_unstemmed	Blood–brain barrier disruption and ventricular enlargement are the earliest neuropathological changes in rats with repeated sub-concussive impacts over 2 weeks
title_sort	blood–brain barrier disruption and ventricular enlargement are the earliest neuropathological changes in rats with repeated sub-concussive impacts over 2 weeks
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/cf82d2fd2ba345389667629116ebde2a
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Blood–brain barrier disruption and ventricular enlargement are the earliest neuropathological changes in rats with repeated sub-concussive impacts over 2 weeks

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