Kallikrein cascades in traumatic spinal cord injury: in vitro evidence for roles in axonopathy and neuron degeneration.

Maja Radulovic, Hyesook Yoon, Nadya Larson, Jianmin Wu, Rachel Linbo, Joshua E. Burda, Eleftherios P. Diamandis, Sachiko I. Blaber, Michael Blaber, Michael G. Fehlings, Isobel A. Scarisbrick

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Kallikreins (KLKs) are a family of 15 secreted serine proteases with emerging roles in neurologic diseases. To illuminate their contributions to the pathophysiology of spinal cord injury (SCI), we evaluated acute through chronic changes in the immunohistochemical appearance of 6 KLKs (KLK1, KLK5, KLK6, KLK7, KLK8, and KLK9) in postmortem human traumatic SCI cases, quantified their RNA expression levels in experimental murine SCI, and assessed the impact of recombinant forms of each enzyme toward murine cortical neurons in vitro. Temporally and spatially distinct changes in KLK expression were observed with partially overlapping patterns between human and murine SCI, including peak elevations (or reductions) during the acute and subacute periods. Kallikrein 9 showed the most marked changes and remained chronically elevated. Importantly, a subset of KLKs (KLK1, KLK5, KLK6, KLK7, and KLK9) were neurotoxic toward primary neurons in vitro. Kallikrein immunoreactivity was also observed in association with swollen axons and retraction bulbs in the human SCI cases examined. Together, these findings demonstrate that elevated levels of a significant subset of KLKs are positioned to contribute to neurodegenerative changes in cases of CNS trauma and disease and, therefore, represent new potential targets for the development of neuroprotective strategies.

Original languageEnglish (US)
Pages (from-to)1072-1089
Number of pages18
JournalJournal of Neuropathology and Experimental Neurology
Volume72
Issue number11
DOIs
StatePublished - Nov 2013

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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    Radulovic, M., Yoon, H., Larson, N., Wu, J., Linbo, R., Burda, J. E., Diamandis, E. P., Blaber, S. I., Blaber, M., Fehlings, M. G., & Scarisbrick, I. A. (2013). Kallikrein cascades in traumatic spinal cord injury: in vitro evidence for roles in axonopathy and neuron degeneration. Journal of Neuropathology and Experimental Neurology, 72(11), 1072-1089. https://doi.org/10.1097/NEN.0000000000000007