Trauma-induced cell swelling in cultured astrocytes

Arumugam R. Jayakumar, K. V.Rama Rao, Kiran S. Panickar, M. Moriyama, P. V.B. Reddy, Michael D. Norenberg

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Brain edema and associated increased intracranial pressure are major consequences of traumatic brain injury that account for most early deaths after traumatic brain injury. An important component of brain edema after traumatic brain injury is astrocyte swelling (cytotoxic edema). To examine the pathophysiologic mechanisms of trauma-induced astrocyte swelling, we used an in vitro fluid percussion trauma model. Exposure of cultured rat astrocytes to 5 atm of pressure resulted in significant cell swelling at 1 to 24 hours posttrauma that was maximal at 3 hours. Because oxidative/nitrosative stress, mitochondrial permeability transition (mPT), and mitogen-activated protein kinases (MAPKs) have been implicated in astrocyte swelling in other neurologic conditions, we examined their potential roles in this model. We previously showed increased free radical generation after in vitro trauma and show here that trauma to astrocytes increased the production of nitric oxide. Trauma also induced mPT and increased phosphorylation (activation) of MAPKs (extracellular signal-regulated kinase 1/2, c-Jun-N-terminal kinase, and p38-MAPK); these changes were diminished by antioxidants and the nitric oxide synthase inhibitor N-nitro-l-arginine methyl ester. Antioxidants, N-nitro-l-arginine methyl ester, the mPT inhibitor cyclosporin A, and inhibitors of MAPKs all significantly diminished trauma-induced astrocyte swelling. These findings demonstrate that direct mechanical injury to cultured astrocytes brings about cell swelling, and that blockade of oxidative/nitrosative stress, mPT, and MAPKs significantly reduce such swelling.

Original languageEnglish (US)
Pages (from-to)417-427
Number of pages11
JournalJournal of neuropathology and experimental neurology
Volume67
Issue number5
DOIs
StatePublished - May 1 2008

Keywords

  • Astrocytes
  • Cell cultures
  • Cell swelling
  • Cytotoxic edema
  • Mitochondrial permeability transition
  • Mitogen-activated protein kinases
  • Nitric oxide
  • Oxidative stress
  • Traumatic brain injury

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

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