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Early Blood–Brain B...
Early Blood–Brain Barrier Impairment as a Pathological Hallmark in a Novel Model of Closed-Head Concussive Brain Injury (CBI) in Mice
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- Blaschke, Stefan J. (författare)
- Jülich Research Centre,University Hospital of Cologne
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- Rautenberg, Nora (författare)
- University Hospital of Cologne,Jülich Research Centre
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- Endepols, Heike (författare)
- University Hospital of Cologne,Jülich Research Centre
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- Jendro, Aileen (författare)
- University Hospital of Cologne
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- Konrad, Jens (författare)
- Jülich Research Centre
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- Vlachakis, Susan (författare)
- University Hospital of Cologne
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Wiedermann, Dirk (författare)
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- Schroeter, Michael (författare)
- Jülich Research Centre,University Hospital of Cologne
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- Hoffmann, Bernd (författare)
- Jülich Research Centre
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- Merkel, Rudolf (författare)
- Jülich Research Centre
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- Marklund, Niklas (författare)
- Lund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUBIN Lab- Lunds laboratorium för neurokirurgisk hjärnskadeforskning,Forskargrupper vid Lunds universitet,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,LUBIN Lab- Lund Brain Injury laboratory for Neurosurgical research,Lund University Research Groups
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- Fink, Gereon R. (författare)
- Jülich Research Centre,University Hospital of Cologne
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- Rueger, Maria A. (författare)
- Jülich Research Centre,University Hospital of Cologne
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(creator_code:org_t)
- 2024
- 2024
- Engelska.
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Ingår i: International Journal of Molecular Sciences. - 1661-6596. ; 25:9
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- Concussion, caused by a rotational acceleration/deceleration injury mild enough to avoid structural brain damage, is insufficiently captured in recent preclinical models, hampering the relation of pathophysiological findings on the cellular level to functional and behavioral deficits. We here describe a novel model of unrestrained, single vs. repetitive concussive brain injury (CBI) in male C56Bl/6j mice. Longitudinal behavioral assessments were conducted for up to seven days afterward, alongside the evaluation of structural cerebral integrity by in vivo magnetic resonance imaging (MRI, 9.4 T), and validated ex vivo by histology. Blood–brain barrier (BBB) integrity was analyzed by means of fluorescent dextran- as well as immunoglobulin G (IgG) extravasation, and neuroinflammatory processes were characterized both in vivo by positron emission tomography (PET) using [18F]DPA-714 and ex vivo using immunohistochemistry. While a single CBI resulted in a defined, subacute neuropsychiatric phenotype, longitudinal cognitive testing revealed a marked decrease in spatial cognition, most pronounced in mice subjected to CBI at high frequency (every 48 h). Functional deficits were correlated to a parallel disruption of the BBB, (R2 = 0.29, p < 0.01), even detectable by a significant increase in hippocampal uptake of [18F]DPA-714, which was not due to activation of microglia, as confirmed immunohistochemically. Featuring a mild but widespread disruption of the BBB without evidence of macroscopic damage, this model induces a characteristic neuro-psychiatric phenotype that correlates to the degree of BBB disruption. Based on these findings, the BBB may function as both a biomarker of CBI severity and as a potential treatment target to improve recovery from concussion.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- blood–brain barrier
- mice
- mild traumatic brain injury
- neuroinflammation
- PET
- repetitive concussion
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Blaschke, Stefan ...
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Rautenberg, Nora
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Endepols, Heike
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Jendro, Aileen
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Konrad, Jens
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Vlachakis, Susan
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visa fler...
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Wiedermann, Dirk
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Schroeter, Micha ...
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Hoffmann, Bernd
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Merkel, Rudolf
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Marklund, Niklas
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Fink, Gereon R.
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Rueger, Maria A.
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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och Neurovetenskaper
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Lunds universitet