Abstract
OBJECTIVE: Traumatic brain injury (TBI) has been shown to induce a significant change in polyamine metabolism. Polyamines and polyamine-dependent calcium influx play an important role in mediating the effects of excitotoxic amino acids at the N-methyl-D-aspartate (NMDA) receptor site. We studied the effects of ifenprodil, known as a noncompetitive inhibitor of polyamine sites at the NMDA receptor, on brain edema formation, blood-brain barrier breakdown, and volume of injury after TBI. METHODS: Experimental TBI was induced in Sprague-Dawley rats by a controlled cortical impact device, functioning at a velocity of 3 m/s to produce a 2-mm deformation. Ifenprodil or saline (10 ms/kg) was injected intraperitoneally immediately after the cortical impact injury and then every 90 minutes until 6 hours after TBI. Blood-brain barrier breakdown was evaluated quantitatively 6 hours after injury by fluorometric assay of Evans blue extravasation. Brain water content, an indicator of brain edema, was measured with the wet-dry method 24 hours after TBI. Injury volume was quantitated from the brain slices stained with 2% cresyl violet solution 7 days after TBI. RESULTS: Blood-brain barrier breakdown was significantly lower in the traumatic cortex of the ifenprodil-treated group than in the saline-treated group (84.4 ± 26.8 μg/g versus 161.8 ± 27 μg/g, respectively, P < 0.05). Brain edema was significantly reduced in the cortex of the ifenprodil-treated group relative to that in the saline-treated group (80.9 ± 0.5% versus 82.4 ± 0.6% respectively, P < 0.05). Ifenprodil treatment reduced injury volume significantly (14.9 ± 8.1 mm3versus 24.4 ± 6.7 mm3, P < 0.05). CONCLUSION: The polyamine-site NMDA receptor antagonist ifenprodil affords significant neuroprotection in a controlled cortical impact brain injury model and may hold promise for the discovery and treatment of the mechanism of delayed neurological deficits after TBI.
Original language | English (US) |
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Pages (from-to) | 399-406 |
Number of pages | 8 |
Journal | Neurosurgery |
Volume | 47 |
Issue number | 2 |
DOIs | |
State | Published - 2000 |
Externally published | Yes |
Keywords
- Blood-brain barrier
- Brain edema
- Ifenprodil
- NMDA receptors
- Polyamines
- Traumatic brain injury
ASJC Scopus subject areas
- Surgery
- Clinical Neurology