Moderately elevated intracranial pressure after diffuse traumatic brain injury is associated with exacerbated neuronal pathology and behavioral morbidity in the rat

J Cereb Blood Flow Metab. 2014 Oct;34(10):1628-36. doi: 10.1038/jcbfm.2014.122. Epub 2014 Jul 16.


Traumatic brain injury (TBI)-induced elevated intracranial pressure (ICP) is correlated with ensuing morbidity/mortality in humans. This relationship is assumed to rely mostly on the recognition that extremely elevated ICP either indicates hematoma/contusions capable of precipitating herniation or alters cerebral perfusion pressure (CPP), which precipitates global ischemia. However, whether subischemic levels of elevated ICP without hematoma/contusion contribute to increased morbidity/mortality remains unknown. To address this knowledge gap, we utilized a model of moderate diffuse TBI in rats followed by either intraventricular ICP monitoring or manual ICP elevation to 20 mm Hg, in which CPP was above ischemic levels. The effects of ICP elevation after TBI on acute and chronic histopathology, as well as on behavioral morbidity, were evaluated. ICP elevation after TBI resulted in increased acute neuronal membrane perturbation and was also associated with reduced neuronal density at 4 weeks after injury. Somatosensory hypersensitivity was exacerbated by ICP elevation and was correlated to the observed neuronal loss. In conclusion, this study indicates that morbidity and increased neuronal damage/death associated with elevated ICP can occur without concurrent global ischemia. Therefore, understanding the pathologies associated with subischemic levels of elevated ICP could lead to the development of better therapeutic strategies for the treatment and management of TBI patients.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain / pathology*
  • Brain / physiopathology
  • Brain Injuries / complications*
  • Brain Injuries / pathology
  • Brain Injuries / physiopathology
  • Hyperesthesia / complications
  • Intracranial Hypertension / complications*
  • Intracranial Hypertension / pathology
  • Intracranial Hypertension / physiopathology
  • Male
  • Neurons / pathology*
  • Rats
  • Rats, Sprague-Dawley
  • Survival Analysis