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 Jun 30;20(13):3223. doi: 10.3390/ijms20133223.


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.

Keywords: BBB; cognitive dysfunction; hypertension; mild brain trauma; vascular injury.

MeSH terms

  • Animals
  • Blood-Brain Barrier / metabolism*
  • Blood-Brain Barrier / pathology
  • Brain Injuries, Traumatic / complications
  • Brain Injuries, Traumatic / metabolism*
  • Brain Injuries, Traumatic / physiopathology
  • Capillary Permeability
  • Cerebral Cortex / metabolism
  • Cognition*
  • Fibrin / metabolism
  • Hippocampus / metabolism
  • Hypertension / complications*
  • Interleukins / metabolism*
  • Male
  • Rats
  • Rats, Inbred SHR
  • Tumor Necrosis Factor-alpha / metabolism*


  • Interleukins
  • Tumor Necrosis Factor-alpha
  • Fibrin