Impaired fibrinolysis and traumatic brain injury in mice

Diego Morales, Tracy McIntosh, Valeria Conte, Scott Fujimoto, David Graham, M. Sean Grady, Sherman C. Stein

Research output: Contribution to journalArticle

Abstract

Traumatic brain injury (TBI) has been associated with intravascular coagulation, which may be a result of thromboplastin released following brain injury. Clots thus formed are lysed by plasmin, which is activated by tissue-type and urokinase-type plasminogen activators (uPA). To evaluate the association between traumatic intravascular coagulation and post-traumatic outcome, uPA knockout (uPA -/-) transgenic mice (n = 12) or wild-type littermates (WT; n = 12) were anesthetized and subjected to controlled cortical impact (CCI) brain injury. A second group of uPA -/- (n = 12) and WT mice (n = 12) were subjected to sham injury. Motor function was assessed over 2 weeks using the composite neuroscore test and cognition (learning) was assessed with the Morris Water Maze (MWM) at 2 weeks post-injury, whereupon the animals were sacrificed for cortical lesion volume analysis. Motor function was significantly worse in the brain-injured uPA -/- mice when compared to brain-injured WT mice at 48 h (p <0.05) and one week post-injury (p <0.05). These dif-ferences resolved by 2 weeks post-injury. There was no significant difference in post-injury cognitive function between uPA -/- mice and WT mice. However, at 2 weeks post-injury, the brain-injured uPA -/- had a significantly larger volume of cortical tissue loss than their WT counterparts (p <0.05). These results demonstrate that the absence of uPA In mice aggravates acute motor deficit and exacerbates cortical tissue loss following CCI brain injury, and suggests a neuroprotective role of the fibrinolytic process following TBI.

Original languageEnglish
Pages (from-to)976-984
Number of pages9
JournalJournal of Neurotrauma
Volume23
Issue number6
DOIs
Publication statusPublished - Jun 2006

Keywords

  • Fibrinolysis
  • Mice
  • Plasminogen
  • Traumatic brain injury
  • uPA

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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    Morales, D., McIntosh, T., Conte, V., Fujimoto, S., Graham, D., Grady, M. S., & Stein, S. C. (2006). Impaired fibrinolysis and traumatic brain injury in mice. Journal of Neurotrauma, 23(6), 976-984. https://doi.org/10.1089/neu.2006.23.976