Mild Traumatic Brain Injury-Induced Disruption of the Blood-Brain Barrier Triggers an Atypical Neuronal Response
被引:10
作者:
Munoz-Ballester, Carmen
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机构:
Virginia Tech Caril, Fralin Biomed Res Inst, Roanoke, VA 24016 USA
Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL 35294 USAVirginia Tech Caril, Fralin Biomed Res Inst, Roanoke, VA 24016 USA
Munoz-Ballester, Carmen
[1
,2
]
Mahmutovic, Dzenis
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机构:
Virginia Tech Caril, Fralin Biomed Res Inst, Roanoke, VA 24016 USA
Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL 35294 USAVirginia Tech Caril, Fralin Biomed Res Inst, Roanoke, VA 24016 USA
Mahmutovic, Dzenis
[1
,2
]
Rafiqzad, Yusuf
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机构:
Virginia Tech Caril, Fralin Biomed Res Inst, Roanoke, VA 24016 USA
Virginia Tech Caril, Sch Neurosci, Blacksburg, VA 24016 USAVirginia Tech Caril, Fralin Biomed Res Inst, Roanoke, VA 24016 USA
Rafiqzad, Yusuf
[1
,3
]
Korot, Alia
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机构:
Virginia Tech Caril, Fralin Biomed Res Inst, Roanoke, VA 24016 USA
Kenyon Coll, Gambier, OH 43022 USAVirginia Tech Caril, Fralin Biomed Res Inst, Roanoke, VA 24016 USA
Korot, Alia
[1
,4
]
Robel, Stefanie
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机构:
Virginia Tech Caril, Fralin Biomed Res Inst, Roanoke, VA 24016 USA
Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL 35294 USA
Virginia Tech Caril, Sch Neurosci, Blacksburg, VA 24016 USAVirginia Tech Caril, Fralin Biomed Res Inst, Roanoke, VA 24016 USA
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
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.
机构:
Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, SwedenKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden
Armulik, Annika
;
Genove, Guillem
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Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, SwedenKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden
Genove, Guillem
;
Mae, Maarja
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机构:
Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, SwedenKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden
Mae, Maarja
;
Nisancioglu, Maya H.
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Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, SwedenKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden
Nisancioglu, Maya H.
;
Wallgard, Elisabet
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Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, SwedenKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden
Wallgard, Elisabet
;
Niaudet, Colin
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机构:
Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, SwedenKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden
Niaudet, Colin
;
He, Liqun
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机构:
Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, SwedenKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden
He, Liqun
;
Norlin, Jenny
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机构:
Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, SwedenKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden
Norlin, Jenny
;
Lindblom, Per
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机构:
AstraZeneca AB, Clin Dev, SE-43183 Molndal, SwedenKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden
Lindblom, Per
;
Strittmatter, Karin
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机构:
Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, SwedenKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden
Strittmatter, Karin
;
Johansson, Bengt R.
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Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Electron Microscopy Unit, SE-40530 Gothenburg, SwedenKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden
Johansson, Bengt R.
;
Betsholtz, Christer
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机构:
Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, SwedenKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden
机构:
Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, SwedenKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden
Armulik, Annika
;
Genove, Guillem
论文数: 0引用数: 0
h-index: 0
机构:
Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, SwedenKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden
Genove, Guillem
;
Mae, Maarja
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机构:
Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, SwedenKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden
Mae, Maarja
;
Nisancioglu, Maya H.
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h-index: 0
机构:
Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, SwedenKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden
Nisancioglu, Maya H.
;
Wallgard, Elisabet
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h-index: 0
机构:
Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, SwedenKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden
Wallgard, Elisabet
;
Niaudet, Colin
论文数: 0引用数: 0
h-index: 0
机构:
Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, SwedenKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden
Niaudet, Colin
;
He, Liqun
论文数: 0引用数: 0
h-index: 0
机构:
Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, SwedenKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden
He, Liqun
;
Norlin, Jenny
论文数: 0引用数: 0
h-index: 0
机构:
Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, SwedenKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden
Norlin, Jenny
;
Lindblom, Per
论文数: 0引用数: 0
h-index: 0
机构:
AstraZeneca AB, Clin Dev, SE-43183 Molndal, SwedenKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden
Lindblom, Per
;
Strittmatter, Karin
论文数: 0引用数: 0
h-index: 0
机构:
Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, SwedenKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden
Strittmatter, Karin
;
Johansson, Bengt R.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Electron Microscopy Unit, SE-40530 Gothenburg, SwedenKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden
Johansson, Bengt R.
;
Betsholtz, Christer
论文数: 0引用数: 0
h-index: 0
机构:
Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, SwedenKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden