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 differences 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.
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