The effect of cyclosporin A on brain edema formation following experimental cortical contusion.
Cyclosporin A (CsA) has been shown by our laboratory and others to be neuroprotective in the experimental animal model of traumatic brain injury. However, we found that the intrathecal administration resulted in a concomitant increase of brain edema. The aim of this study was to assess whether intravascular administration may also influence brain edema formation. This project includes two independent series in which different doses of CsA were intravenously given to Sprague-Dawley rats of each group. In the first series, the animals were exposed to focal brain injury by a controlled cortical impact (CCI, 6 m/sec, 3 mm depth) and randomized into the following two groups: 20 mg/kg CsA and control vehicle. In the second series, animals were also injured by CCI and randomized into 35 mg/kg CsA and control vehicle. The intravenous continuous (1 h) infusion was begun 30 minutes after the insult. All animals were sacrificed at 24 hours post injury to assess the brain water content using the gravimetric method. Intravenously-administrated CsA of either 20 or 35 mg/kg did not significantly change the brain water content. We therefore suggest that an intravascular route may be better for CsA administration because the intrathecal injection may exacerbate brain edema as found in our previous study.
Fukui
S
S
Division of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298-0508, USA.
Signoretti
S
S
Dunbar
J G
JG
Marmarou
A
A
D000818:Animals; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology* / Q000378:metabolism; D001930:Brain Injuries / Q000150:complications*; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018696:Neuroprotective Agents; D016572:Cyclosporine