Increase in cerebrovascular permeability leads to fibrinogen‐cellular prion protein complex formation after traumatic brain injury (672.1)

Traumatic brain injury (TBI) is the most common cause of death and disability. It is accompanied with development of inflammation and thus linked to increased content of inflammatory mediators including fibrinogen (Fg). It is known that TBI is associated with loss of memory that can be affected by the level of cellular prion protein (PrPC). We tested the hypothesis that TBI‐induced an increase in cerebrovascular permeability leads to Fg exstravasation in pericontusional area through activation of MMP‐9. Deposited Fg contributes to formation of Fg‐PrPC complex and can be related to loss of short‐term memory. Pial venular leakage was observed by intravital fluorescence microscopy in male wild‐type (WT, C57BL/6J) and MMP‐9 gene knockout (MMP9‐/‐) mice after TBI. Fg deposition and formation of Fg‐PrPC complex were assessed by immunohistochemistry. Short‐term memory of mice was estimated by a novel object recognition test. Cerebrovascular leakage, Fg deposition, and it’s co‐localization with PrPC were increased after TBI in each experimental group compared to those in respective sham‐operated mice. However, they were greater in WT than in MMP9‐/‐ mice. Thus, our data suggest that TBI‐induced increased cerebrovascular permeability and the resultant Fg deposition leads to Fg‐PrPC complex formation. The latter can be involved in loss of memory. These results indicate a novel role of Fg in post‐TBI pathology. Grant Funding Source : NIH P30 GM103507 and NS084823