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

被引:10
作者
Munoz-Ballester, Carmen [1 ,2 ]
Mahmutovic, Dzenis [1 ,2 ]
Rafiqzad, Yusuf [1 ,3 ]
Korot, Alia [1 ,4 ]
Robel, Stefanie [1 ,2 ,3 ]
机构
[1] Virginia Tech Caril, Fralin Biomed Res Inst, Roanoke, VA 24016 USA
[2] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL 35294 USA
[3] Virginia Tech Caril, Sch Neurosci, Blacksburg, VA 24016 USA
[4] Kenyon Coll, Gambier, OH 43022 USA
基金
美国国家卫生研究院;
关键词
traumatic brain injury; acute TBI; chronic TBI; spines; primary injury; secondary injury; NeuN; concussion; DENDRITIC SPINES; TGF-BETA; FIBRINOGEN; INFLAMMATION; ASTROCYTES; MECHANISMS; PLASTICITY; PATHOLOGY; GEOMETRY; MODEL;
D O I
10.3389/fncel.2022.821885
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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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页数:15
相关论文
共 60 条
[1]   Fibrinogen signal transduction as a mediator and therapeutic target in inflammation: Lessons from multiple sclerosis [J].
Adams, R. A. ;
Schachtrup, C. ;
Davalos, D. ;
Tsigelny, I. ;
Akassoglou, K. .
CURRENT MEDICINAL CHEMISTRY, 2007, 14 (27) :2925-2936
[2]   Anatomical and physiological plasticity of dendritic spines [J].
Alvarez, Veronica A. ;
Sabatini, Bernardo L. .
ANNUAL REVIEW OF NEUROSCIENCE, 2007, 30 :79-97
[3]   Pericytes regulate the blood-brain barrier [J].
Armulik, Annika ;
Genove, Guillem ;
Mae, Maarja ;
Nisancioglu, Maya H. ;
Wallgard, Elisabet ;
Niaudet, Colin ;
He, Liqun ;
Norlin, Jenny ;
Lindblom, Per ;
Strittmatter, Karin ;
Johansson, Bengt R. ;
Betsholtz, Christer .
NATURE, 2010, 468 (7323) :557-U231
[4]   Long-Term Consequences of Traumatic Brain Injury: Current Status of Potential Mechanisms of Injury and Neurological Outcomes [J].
Bramlett, Helen M. ;
Dietrich, W. Dalton .
JOURNAL OF NEUROTRAUMA, 2015, 32 (23) :1834-1848
[5]   Mechanical injuries of neurons induce tau mislocalization to dendritic spines and tau-dependent synaptic dysfunction [J].
Braun, Nicholas J. ;
Yao, Katherine R. ;
Alford, Patrick W. ;
Liao, Dezhi .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2020, 117 (46) :29069-29079
[6]   Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice [J].
Bush, TG ;
Puvanachandra, N ;
Horner, CH ;
Polito, A ;
Ostenfeld, T ;
Svendsen, CN ;
Mucke, L ;
Johnson, MH ;
Sofroniew, MV .
NEURON, 1999, 23 (02) :297-308
[7]   Role of the calcium-binding protein parvalbumin in short-term synaptic plasticity [J].
Caillard, O ;
Moreno, H ;
Schwaller, B ;
Llano, I ;
Celio, MR ;
Marty, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (24) :13372-13377
[8]   GABAergic Disinhibition and Impaired KCC2 Cotransporter Activity Underlie Tumor-Associated Epilepsy [J].
Campbell, Susan L. ;
Robel, Stefanie ;
Cuddapah, Vishnu A. ;
Robert, Stephanie ;
Buckingham, Susan C. ;
Kahle, Kristopher T. ;
Sontheimer, Harald .
GLIA, 2015, 63 (01) :23-36
[9]   Time course of cellular pathology after controlled cortical impact injury [J].
Chen, S ;
Pickard, JD ;
Harris, NG .
EXPERIMENTAL NEUROLOGY, 2003, 182 (01) :87-102
[10]  
Cooper G.M., 2000, CELL MOL APPROACH, V2nd, DOI [10.1002/9781118539385.ch17, DOI 10.1002/9781118539385.CH17]