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Mild Traumatic Brain Injury-Induced Disruption of the Blood-Brain Barrier Triggers an Atypical Neuronal Response

Mild TBI (mTBI), which affects 75% of TBI survivors or more than 50 million people worldwide each year, can lead to consequences including sleep disturbances, cognitive impairment, mood swings, and post-traumatic epilepsy in a subset of patients. To interrupt the progression of these comorbidities,...

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Autores principales: Munoz-Ballester, Carmen, Mahmutovic, Dzenis, Rafiqzad, Yusuf, Korot, Alia, Robel, Stefanie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8894613/
https://www.ncbi.nlm.nih.gov/pubmed/35250487
http://dx.doi.org/10.3389/fncel.2022.821885
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author Munoz-Ballester, Carmen
Mahmutovic, Dzenis
Rafiqzad, Yusuf
Korot, Alia
Robel, Stefanie
author_facet Munoz-Ballester, Carmen
Mahmutovic, Dzenis
Rafiqzad, Yusuf
Korot, Alia
Robel, Stefanie
author_sort Munoz-Ballester, Carmen
collection PubMed
description Mild TBI (mTBI), which affects 75% of TBI survivors or more than 50 million people worldwide each year, can lead to consequences including sleep disturbances, cognitive impairment, mood swings, and post-traumatic epilepsy in a subset of patients. To interrupt the progression of these comorbidities, identifying early pathological events is key. Recent studies have shown that microbleeds, caused by mechanical impact, persist for months after mTBI and are correlated to worse mTBI outcomes. However, the impact of mTBI-induced blood-brain barrier damage on neurons is yet to be revealed. We used a well-characterized mouse model of mTBI that presents with frequent and widespread but size-restricted damage to the blood-brain barrier to assess how neurons respond to exposure of blood-borne factors in this pathological context. We used immunohistochemistry and histology to assess the expression of neuronal proteins in excitatory and inhibitory neurons after mTBI. We observed that the expression of NeuN, Parvalbumin, and CamKII was lost within minutes in areas with blood-brain barrier disruption. Yet, the neurons remained alive and could be detected using a fluorescent Nissl staining even 6 months later. A similar phenotype was observed after exposure of neurons to blood-borne factors due to endothelial cell ablation in the absence of a mechanical impact, suggesting that entrance of blood-borne factors into the brain is sufficient to induce the neuronal atypical response. Changes in postsynaptic spines were observed indicative of functional changes. Thus, this study demonstrates That exposure of neurons to blood-borne factors causes a rapid and sustained loss of neuronal proteins and changes in spine morphology in the absence of neurodegeneration, a finding that is likely relevant to many neuropathologies.
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spelling pubmed-88946132022-03-05 Mild Traumatic Brain Injury-Induced Disruption of the Blood-Brain Barrier Triggers an Atypical Neuronal Response Munoz-Ballester, Carmen Mahmutovic, Dzenis Rafiqzad, Yusuf Korot, Alia Robel, Stefanie Front Cell Neurosci Cellular Neuroscience Mild TBI (mTBI), which affects 75% of TBI survivors or more than 50 million people worldwide each year, can lead to consequences including sleep disturbances, cognitive impairment, mood swings, and post-traumatic epilepsy in a subset of patients. To interrupt the progression of these comorbidities, identifying early pathological events is key. Recent studies have shown that microbleeds, caused by mechanical impact, persist for months after mTBI and are correlated to worse mTBI outcomes. However, the impact of mTBI-induced blood-brain barrier damage on neurons is yet to be revealed. We used a well-characterized mouse model of mTBI that presents with frequent and widespread but size-restricted damage to the blood-brain barrier to assess how neurons respond to exposure of blood-borne factors in this pathological context. We used immunohistochemistry and histology to assess the expression of neuronal proteins in excitatory and inhibitory neurons after mTBI. We observed that the expression of NeuN, Parvalbumin, and CamKII was lost within minutes in areas with blood-brain barrier disruption. Yet, the neurons remained alive and could be detected using a fluorescent Nissl staining even 6 months later. A similar phenotype was observed after exposure of neurons to blood-borne factors due to endothelial cell ablation in the absence of a mechanical impact, suggesting that entrance of blood-borne factors into the brain is sufficient to induce the neuronal atypical response. Changes in postsynaptic spines were observed indicative of functional changes. Thus, this study demonstrates That exposure of neurons to blood-borne factors causes a rapid and sustained loss of neuronal proteins and changes in spine morphology in the absence of neurodegeneration, a finding that is likely relevant to many neuropathologies. Frontiers Media S.A. 2022-02-18 /pmc/articles/PMC8894613/ /pubmed/35250487 http://dx.doi.org/10.3389/fncel.2022.821885 Text en Copyright © 2022 Munoz-Ballester, Mahmutovic, Rafiqzad, Korot and Robel. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular Neuroscience
Munoz-Ballester, Carmen
Mahmutovic, Dzenis
Rafiqzad, Yusuf
Korot, Alia
Robel, Stefanie
Mild Traumatic Brain Injury-Induced Disruption of the Blood-Brain Barrier Triggers an Atypical Neuronal Response
title Mild Traumatic Brain Injury-Induced Disruption of the Blood-Brain Barrier Triggers an Atypical Neuronal Response
title_full Mild Traumatic Brain Injury-Induced Disruption of the Blood-Brain Barrier Triggers an Atypical Neuronal Response
title_fullStr Mild Traumatic Brain Injury-Induced Disruption of the Blood-Brain Barrier Triggers an Atypical Neuronal Response
title_full_unstemmed Mild Traumatic Brain Injury-Induced Disruption of the Blood-Brain Barrier Triggers an Atypical Neuronal Response
title_short Mild Traumatic Brain Injury-Induced Disruption of the Blood-Brain Barrier Triggers an Atypical Neuronal Response
title_sort mild traumatic brain injury-induced disruption of the blood-brain barrier triggers an atypical neuronal response
topic Cellular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8894613/
https://www.ncbi.nlm.nih.gov/pubmed/35250487
http://dx.doi.org/10.3389/fncel.2022.821885
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