Single mild traumatic brain injury induces persistent disruption of the blood-brain barrier, neuroinflammation and cognitive decline in hypertensive rats

Nikolett Szarka, Luca Toth, Andras Czigler, Zoltan Kellermayer, Zoltan Ungvari, Krisztina Amrein, Endre Czeiter, Zsolt Kristof Bali, Sai Ambika Tadepalli, Matyas Wahr, Istvan Hernadi, Akos Koller, Andras Buki, Peter Toth

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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 normotensiveWistar 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.

Original languageEnglish
Article number3223
JournalInternational journal of molecular sciences
Volume20
Issue number13
DOIs
Publication statusPublished - Jul 1 2019

Keywords

  • BBB
  • Cognitive dysfunction
  • Hypertension
  • Mild brain trauma
  • Vascular injury

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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  • Cite this

    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. (2019). Single mild traumatic brain injury induces persistent disruption of the blood-brain barrier, neuroinflammation and cognitive decline in hypertensive rats. International journal of molecular sciences, 20(13), [3223]. https://doi.org/10.3390/ijms20133223