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Mild traumatic brain injury-induced persistent blood-brain barrier disruption is prevented by cyclosporine A treatment in hypertension

Lendvai-Emmert, Dominika (författare)
Department of Neurosurgery, Medical School, University of Pecs, Pecs, Hungary; Neurotrauma Research Group, Szentagothai Research Centre, University of Pecs, Pecs, Hungary
Magyar-Sumegi, Zsofia Dina (författare)
Department of Neurosurgery, Medical School, University of Pecs, Pecs, Hungary; Neurotrauma Research Group, Szentagothai Research Centre, University of Pecs, Pecs, Hungary
Hegedus, Emoke (författare)
Department of Neurosurgery, Medical School, University of Pecs, Pecs, Hungary; Neurotrauma Research Group, Szentagothai Research Centre, University of Pecs, Pecs, Hungary; Department of Anaesthesiology and Intensive Therapy, Medical School, University of Pecs, Pecs, Hungary
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Szarka, Nikolett (författare)
Department of Primary Health Care, Medical School, University of Pecs, Pecs, Hungary
Fazekas, Balint (författare)
Department of Neurosurgery, Medical School, University of Pecs, Pecs, Hungary; Neurotrauma Research Group, Szentagothai Research Centre, University of Pecs, Pecs, Hungary
Amrein, Krisztina (författare)
Department of Neurosurgery, Medical School, University of Pecs, Pecs, Hungary; Neurotrauma Research Group, Szentagothai Research Centre, University of Pecs, Pecs, Hungary; ELKH-PTE Clinical Neuroscience MR Research Group, University of Pecs, Pecs, Hungary
Czeiter, Endre (författare)
Department of Neurosurgery, Medical School, University of Pecs, Pecs, Hungary; Neurotrauma Research Group, Szentagothai Research Centre, University of Pecs, Pecs, Hungary; ELKH-PTE Clinical Neuroscience MR Research Group, University of Pecs, Pecs, Hungary
Büki, Andras, 1966- (författare)
Örebro universitet,Institutionen för medicinska vetenskaper,Department of Neurosurgery, Medical School, University of Pecs, Pecs, Hungary; Department of Neurosurgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
Ungvari, Zoltan (författare)
Department of Neurosurgery, Vascular Cognitive Impairment and Neurodegeneration Program, Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States; Department of Public Health, International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine, Semmelweis University, Budapest, Hungary
Toth, Peter (författare)
Department of Neurosurgery, Medical School, University of Pecs, Pecs, Hungary; Neurotrauma Research Group, Szentagothai Research Centre, University of Pecs, Pecs, Hungary; ELKH-PTE Clinical Neuroscience MR Research Group, University of Pecs, Pecs, Hungary; Department of Neurosurgery, Vascular Cognitive Impairment and Neurodegeneration Program, Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States; Department of Public Health, International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine, Semmelweis University, Budapest, Hungary
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 (creator_code:org_t)
Frontiers Media S.A. 2023
2023
Engelska.
Ingår i: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 14
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • INTRODUCTION: Mild traumatic brain injury (mTBI) and hypertension synergize to induce persistent disruption of the blood-brain barrier (BBB), neuroinflammation and cognitive decline. However, the underlying mechanisms are not known. Cerebral production of Cyclophilin A (CyPA) is induced in hypertension and after TBI, and it was demonstrated to activate the nuclear factor-κB (NF-kB)- matrix-metalloproteinase-9 (MMP-9) pathway in cerebral vessels leading to BBB disruption.METHODS: To test the role of CyPA in mTBI- and hypertension-induced BBB disruption we induced mTBI in normotensive and spontaneously hypertensive rats (SHR), then the animals were treated with cyclosporine A (a specific inhibitor of CyPA production) or vehicle for 7 days. We assessed BBB permeability and integrity, cerebral expression and activity of the CyPA-NF-kB-MMP-9 pathway, extravasation of fibrin and neuroinflammation.RESULTS: We found that mild TBI induced BBB disruption and upregulation of the CyPA-NF-kB-MMP-9 pathway in hypertension, which were prevented by blocking CyPA. Cyclosporine treatment and preservation of BBB function prevented accumulation of blood-derived fibrin in the brain parenchyma of hypertensive rats after mTBI and reversed increased neuroinflammation.DISCUSSION: We propose that mTBI and hypertension interact to promote BBB disruption via the CyPA-NF-kB-MMP-9 pathway, and inhibition of cyclophilin production after mTBI may exert neuroprotection and improve cognitive function in hypertensive patients.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

BBB
CyPA
hypertension
mTBI
neuroinflammation

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