Cyclosporin A limits calcium-induced axonal damage following traumatic brain injury

David O. Okonkwo, A. Büki, Robert Siman, John T. Povlishock

Research output: Contribution to journalArticle

164 Citations (Scopus)

Abstract

IN traumatic axonal injury, Ca2+- influx across a focally damaged axolemma precipitates local mitochondrial failure, degradation of the subaxolemmal spectrin network and compaction of neurofilaments, which collectively contribute to axonal failure. In previous studies, cyclosporin A pretreatment preserved mitochondrial integrity and attenuated axonal failure following trauma. Here we investigate whether this CsA-linked protection was related to the concomitant blunting of intra-axonal, Ca2+-induced cytoskeletal changes in traumatic axonal injury, assessed with antibodies targeting spectrin proteolysis and neurofilament compaction. CsA pretreatment dramatically reduced Ca2+-induced cytoskeletal damage following injury; CsA-treated rats, compared with vehicle-treated rats, displayed a 70% decrease in immunoreactive/damaged profiles. We suggest that CsA-mediated preservation of mitochondrial integrity enables the restoration of ionic and metabolic homeostasis thereby short-circuiting Ca2+-induced proteolysis in injured axons.

Original languageEnglish
Pages (from-to)353-358
Number of pages6
JournalNeuroReport
Volume10
Issue number2
Publication statusPublished - Feb 5 1999

Fingerprint

Cyclosporine
Calcium
Spectrin
Intermediate Filaments
Wounds and Injuries
Proteolysis
Axons
Homeostasis
Traumatic Brain Injury
Antibodies

Keywords

  • Axonal injury
  • Calpain
  • Cyclosporin A
  • Mitochondrial permeability transition
  • PT pore
  • Trauma

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Okonkwo, D. O., Büki, A., Siman, R., & Povlishock, J. T. (1999). Cyclosporin A limits calcium-induced axonal damage following traumatic brain injury. NeuroReport, 10(2), 353-358.

Cyclosporin A limits calcium-induced axonal damage following traumatic brain injury. / Okonkwo, David O.; Büki, A.; Siman, Robert; Povlishock, John T.

In: NeuroReport, Vol. 10, No. 2, 05.02.1999, p. 353-358.

Research output: Contribution to journalArticle

Okonkwo, DO, Büki, A, Siman, R & Povlishock, JT 1999, 'Cyclosporin A limits calcium-induced axonal damage following traumatic brain injury', NeuroReport, vol. 10, no. 2, pp. 353-358.
Okonkwo, David O. ; Büki, A. ; Siman, Robert ; Povlishock, John T. / Cyclosporin A limits calcium-induced axonal damage following traumatic brain injury. In: NeuroReport. 1999 ; Vol. 10, No. 2. pp. 353-358.
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