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Single Mild Traumatic Brain Injury Induces Persistent Disruption of the Blood-Brain Barrier, Neuroinflammation and Cognitive Decline in Hypertensive Rats

1
Department of Neurosurgery and Szentagothai Research Center, University of Pecs, Medical School, Ret u. 2, H-7623 Pecs, Hungary
2
Institute for Translational Medicine, Medical School, University of Pecs, Szigeti ut 12, H-7624 Pecs, Hungary
3
Clinical Medicine Doctoral School, University of Szeged, Tisza Lajos krt. 109., H-6725 Szeged, Hungary
4
Department of Immunology and Biotechnology, University of Pecs, Medical School, Szigeti ut 12, H-7624 Pecs, Hungary
5
Reynolds Oklahoma Center on Aging, Donald W. Reynolds Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
6
MTA-PTE Clinical Neuroscience MR Research Group, Ret u. 2, H-7623 Pecs, Hungary
7
Translational Neuroscience Research Group, Szentagothai Research Center, University of Pecs, Ifjusag utja 20, H-7624 Pecs, Hungary
8
Grastyan Translational Research Center, University of Pecs, Ifjusag utja 6, H-7624 Pecs, Hungary
9
Cellular Neurobiology, Institute of Physiology, Medical School, University of Pecs, Szigeti ut 12, H-7624 Pecs, Hungary
10
Department of Experimental Neurobiology, Faculty of Sciences, University of Pecs, Ifjusag utja 6, H-7624 Pecs, Hungary
11
Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, Ulloi ut 26, H-1085 Budapest, Hungary
12
Department of Physiology, New York Medical College, Valhalla, NY 10595, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(13), 3223; https://doi.org/10.3390/ijms20133223
Received: 15 May 2019 / Revised: 19 June 2019 / Accepted: 28 June 2019 / Published: 30 June 2019
Traumatic brain injury (TBI) induces blood-brain barrier (BBB) disruption, which contributes to secondary injury of brain tissue and development of chronic cognitive decline. However, single mild (m)TBI, the most frequent form of brain trauma disrupts the BBB only transiently. We hypothesized, that co-morbid conditions exacerbate persistent BBB disruption after mTBI leading to long term cognitive dysfunction. Since hypertension is the most important cerebrovascular risk factor in populations prone to mild brain trauma, we induced mTBI in normotensive Wistar and spontaneously hypertensive rats (SHR) and we assessed BBB permeability, extravasation of blood-borne substances, neuroinflammation and cognitive function two weeks after trauma. We found that mTBI induced a significant BBB disruption two weeks after trauma in SHRs but not in normotensive Wistar rats, which was associated with a significant accumulation of fibrin and increased neuronal expression of inflammatory cytokines TNFα, IL-1β and IL-6 in the cortex and hippocampus. SHRs showed impaired learning and memory two weeks after mild TBI, whereas cognitive function of normotensive Wistar rats remained intact. Future studies should establish the mechanisms through which hypertension and mild TBI interact to promote persistent BBB disruption, neuroinflammation and cognitive decline to provide neuroprotection and improve cognitive function in patients with mTBI. View Full-Text
Keywords: hypertension; vascular injury; mild brain trauma; BBB; cognitive dysfunction hypertension; vascular injury; mild brain trauma; BBB; cognitive dysfunction
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Szarka, N.; Toth, L.; Czigler, A.; Kellermayer, Z.; Ungvari, Z.; Amrein, K.; Czeiter, E.; Bali, Z.K.; Tadepalli, S.A.; Wahr, M.; Hernadi, I.; Koller, A.; Buki, A.; Toth, P. Single Mild Traumatic Brain Injury Induces Persistent Disruption of the Blood-Brain Barrier, Neuroinflammation and Cognitive Decline in Hypertensive Rats. Int. J. Mol. Sci. 2019, 20, 3223.

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