Background: Establishment of a traumatic brain injury (TBI)-sensitive biomarker or identification of a key therapeutic agent would significantly improve clinicians' efforts to diagnose and treat TBI, thereby promoting improved outcomes for patients. Numerous studies support the role of kallikrein-6 (Klk6) as a critical component of neuroinflammation and demyelination. This study assesses whether Klk6 is implicated in the secondary mechanisms of TBI and subsequently if serum levels of Klk6 are useable as a biomarker.
Methods: The abundance of Klk6 following controlled cortical impact (CCI) of the medial prefrontal cortex to a depth of either 3.0 mm (severe) or 1.5 mm (moderate) was quantified. Uninjured and rats subjected to craniotomy-only were used as controls. Protein levels were quantified with Western-blotting, enzyme-linked immunosorbent assay and immunohistochemistry.
Results: Severe and moderate CCI resulted in significant elevation of Klk6 in the contusion-core (~12-fold-increase, p < 0.0001) and serum (~5-fold-increase, p < 0.01) compared to controls. In all cases, Klk6 elevation was resolved within 72 hours.
Conclusion: Serum levels of Klk6 are a statistically significant indicator of TBI 24 hours after CCI and thus may be of great utility to clinicians as a biomarker. These data strongly implicate Klk6 as a player in the neuroinflammation processes following CCI, although the specific mechanisms remain to be characterized.