Neuroprotective effects of citicoline on brain edema and blood-brain barrier breakdown after traumatic brain injury

Mustafa K. Başkaya, Aclan Doǧan, A. Muralikrishna Rao, Robert J. Dempsey

Research output: Contribution to journalArticlepeer-review

100 Scopus citations


Object. Cytidine 5'-diphosphocholine (CDPC), or citicoline, is a naturally occurring endogenous compound that has been reported to provide neuroprotective effects after experimental cerebral ischemia. However, in no study has such protection been shown after traumatic brain injury (TBI). In this study the authors examined the effect of CDPC on secondary injury factors, brain edema and blood-brain barrier (BBB) breakdown, after TBI. Methods. After anesthesia had been induced in Sprague-Dawley rats by using 1.5% halothane, an experimental TBI was created using a controlled cortical impact (CCI) device with a velocity of 3 m/second, resulting in a 2-mm deformation. Four sham-operated control animals used for brain edema and BBB breakdown studies underwent the same surgical procedure, but received no injury. Brain edema was evaluated using the wet-dry method 24 hours postinjury, and BBB breakdown was evaluated by measuring Evans blue dye (EBD) extravasation with fluorescein 6 hours after TBI. The animals received intraperitoneal injections of CDPC (50, 100, or 400 mg/kg two times after TBI [eight-10 animals in each group]) or saline (eight animals) after TBI. Traumatic brain injury induced an increase in the percentage of water content and in EBD extravasation in the injured cortex and the ipsilateral hippocampus. No significant benefit from CDPC treatment was observed at a dose of 50 mg/kg. Cytidine 5'-diphosphocholine at a dose of 100 mg/kg attenuated EBD extravasation in both regions, although it reduced brain edema only in the injured cortex. In both regions, 400 mg/kg of CDPC significantly decreased brain edema and BBB breakdown. Conclusions. This is the first report in which dose-dependent neuroprotective effects of CDPC have been demonstrated in the injured cortex as well as in the hippocampus, a brain region known to be vulnerable to injury, after experimental TBI. The results of this study suggest that CDPC is an effective neuroprotective agent on secondary injuries that appear following TBI.

Original languageEnglish (US)
Pages (from-to)448-452
Number of pages5
JournalJournal of neurosurgery
Issue number3
StatePublished - Mar 2000
Externally publishedYes


  • Blood-brain barrier
  • Brain edema
  • Citicoline
  • Traumatic brain injury

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology


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