Post-traumatic cytotoxic edema is directly related to mitochondrial function

Eugene Vlodavsky, Eilam Palzur, Mona Shehadeh, Jean F. Soustiel

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Cerebral edema represents a major threat following traumatic brain injury. However, therapeutic measures for control of intracranial pressure alone have failed to restore cerebral metabolism and improve neurological outcome. Since mitochondrial damage results in ATP depletion and deactivation of membrane ionic pumps, we hypothesized that modulation of ATP bioavailability may directly affect cytotoxic edema. Intracranial pressure measurements were performed in Sprague-Dawley rats treated by intraperitoneal injection of dimethylsulfoxide (vehicle), cyclosporine A (CsA), or Oligomycin B (OligB) following cortical contusion and further correlated with water content, mitochondrial damage, and electron microscopic assessment of neuronal and axonal edema. As hypothesized, ultra-structural figures of edema closely correlated with intracranial pressure elevation, increased water content and mitochondrial membrane permeabilization expressed by loss of transmembrane mitochondrial potential. Further, mitochondrial damage evidenced ultra-structurally by figures of swollen mitochondria with severely distorted cristae correlated with both cytotoxic edema and mitochondrial dysfunction. Importantly, cerebral edema and mitochondrial impairment were significantly worsened by treatment with OligB, whereas a noticeable improvement could be observed in animals that received injections of CsA. Since OligB and CsA are responsible for symmetrical and opposite effects on oxidative metabolism, these findings support the hypothesis of a causative relationship between edema and mitochondrial function.

Original languageEnglish
Pages (from-to)166-177
Number of pages12
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number1
StatePublished - 1 Jan 2017

Bibliographical note

Publisher Copyright:
© 2015 The Author(s).


  • Cerebral metabolism
  • cytotoxic edema
  • mitochondria
  • mitochondrial permeability transition
  • traumatic brain injury


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