Polyamine catabolism is enhanced after traumatic brain injury

Kamyar Zahedi, Francis Huttinger, Ryan Morrison, Tracy Murray Stewart, Robert A Casero, Kenneth I. Strauss

Research output: Contribution to journalArticle

Abstract

Polyamines spermine and spermidine are highly regulated, ubiquitous aliphatic cations that maintain DNA structure and function as immunomodulators and as antioxidants. Polyamine homeostasis is disrupted after brain injuries, with concomitant generation of toxic metabolites that may contribute to secondary injuries. To test the hypothesis of increased brain polyamine catabolism after traumatic brain injury (TBI), we determined changes in catabolic enzymes and polyamine levels in the rat brain after lateral controlled cortical impact TBI. Spermine oxidase (SMO) catalyzes the degradation of spermine to spermidine, generating H2O2 and aminoaldehydes. Spermidine/spermine-N1-acetyltransferase (SSAT) catalyzes acetylation of these polyamines, and both are further oxidized in a reaction that generates putrescine, H2O2, and aminoaldehydes. In a rat cortical impact model of TBI, SSAT mRNA increased subacutely (6-24h) after TBI in ipsilateral cortex and hippocampus. SMO mRNA levels were elevated late, from 3 to 7 days post-injury. Polyamine catabolism increased as well. Spermine levels were normal at 6h and decreased slightly at 24h, but were normal again by 72h post-injury. Spermidine levels also decreased slightly (6-24h), then increased by ∼50% at 72h post-injury. By contrast, normally low putrescine levels increased up to sixfold (6-72h) after TBI. Moreover, N-acetylspermidine (but not N-acetylspermine) was detectable (24-72h) near the site of injury, consistent with increased SSAT activity. None of these changes were seen in the contralateral hemisphere. Immunohistochemical confirmation indicated that SSAT and SMO were expressed throughout the brain. SSAT-immunoreactivity (SSAT-ir) increased in both neuronal and nonneuronal (likely glial) populations ipsilateral to injury. Interestingly, bilateral increases in cortical SSAT-ir neurons occurred at 72h post-injury, whereas hippocampal changes occurred only ipsilaterally. Prolonged increases in brain polyamine catabolism are the likely cause of loss of homeostasis in this pathway. The potential for simple therapeutic interventions (e.g., polyamine supplementation or inhibition of polyamine oxidation) is an exciting implication of these studies.

Original languageEnglish (US)
Pages (from-to)515-525
Number of pages11
JournalJournal of Neurotrauma
Volume27
Issue number3
DOIs
StatePublished - Mar 1 2010

Fingerprint

Spermine
Polyamines
Wounds and Injuries
Spermidine
Putrescine
Brain
Homeostasis
Traumatic Brain Injury
Messenger RNA
Poisons
Immunologic Factors
Acetylation
Neuroglia
Brain Injuries
diamine N-acetyltransferase
Cations
Hippocampus
Antioxidants
Neurons
DNA

Keywords

  • Brain injuries
  • Colocalization immunofluorescence
  • Gene expression
  • Polyamine back-conversion
  • Polyamine quantification
  • Polyamine therapeutic potential
  • Spermidine=spermine-N1-acetyltransferase (SSAT)
  • Spermine oxidase (SMO)
  • Time course

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Polyamine catabolism is enhanced after traumatic brain injury. / Zahedi, Kamyar; Huttinger, Francis; Morrison, Ryan; Murray Stewart, Tracy; Casero, Robert A; Strauss, Kenneth I.

In: Journal of Neurotrauma, Vol. 27, No. 3, 01.03.2010, p. 515-525.

Research output: Contribution to journalArticle

Zahedi, Kamyar ; Huttinger, Francis ; Morrison, Ryan ; Murray Stewart, Tracy ; Casero, Robert A ; Strauss, Kenneth I. / Polyamine catabolism is enhanced after traumatic brain injury. In: Journal of Neurotrauma. 2010 ; Vol. 27, No. 3. pp. 515-525.
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