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Dextromethorphan protects against cerebral injury following transient focal ischemia in rabbits
G K Steinberg1, C P George, R DeLaPaz
1Division of Neurosurgery, Stanford University Medical Center, California.
Abstract:
We investigated dextromethorphan, both a dextrorotatory opioid derivative and a clinically tested N-methyl-D-aspartate (NMDA) receptor antagonist, in a rabbit model of transient focal cerebral ischemia. Fourteen rabbits were randomly assigned to treatment with a 20 mg/kg i.v. loading dose followed by a 10 mg/kg/hr infusion of 0.4% dextromethorphan in normal saline or with an equivalent volume of normal saline alone. One hour after treatment, the rabbits underwent a 1-hour occlusion of the left internal carotid and anterior cerebral arteries followed by 4 hours of reperfusion. The seven dextromethorphan-treated rabbits showed a significant decrease in the area of neocortical severe ischemic neuronal damage (10.5%) compared with the seven normal saline-treated controls (49.6%, p less than 0.001). The dextromethorphan-treated rabbits also demonstrated significantly smaller areas of cortical edema (10.2%) on magnetic resonance imaging than the controls (38.6%, p less than 0.01). Analysis of somatosensory evoked potentials revealed recovery of the ipsilateral amplitude to contralateral values within 5 minutes of reperfusion in the dextromethorphan-treated rabbits but not in the controls (p less than 0.01). In our rabbit model of transient focal cerebral ischemia, dextromethorphan appears to protect the brain against ischemic neuronal damage and edema, as well as to promote neurophysiologic recovery. This clinically available drug should be further investigated as having potential therapeutic value in the treatment of stroke.
Insights
Dextromethorphan significantly reduced brain damage and swelling in a rabbit stroke model. This common medication shows promise for treating ischemic stroke and improving neurological recovery.
Area of Science:
- Neuroscience
- Pharmacology
- Cerebrovascular Research
Background:
- Transient focal cerebral ischemia is a leading cause of stroke-related disability.
- N-methyl-D-aspartate (NMDA) receptor antagonists are being explored for neuroprotection.
- Dextromethorphan is a clinically available NMDA receptor antagonist.
Purpose of the Study:
- To evaluate the neuroprotective effects of dextromethorphan in a rabbit model of transient focal cerebral ischemia.
- To assess dextromethorphan's impact on ischemic neuronal damage, cerebral edema, and neurophysiological recovery.
Main Methods:
- Fourteen rabbits were randomly assigned to receive dextromethorphan or saline.
- A transient focal cerebral ischemia model was induced via arterial occlusion.
- Magnetic resonance imaging (MRI) and somatosensory evoked potentials (SEPs) were used for assessment.
Main Results:
- Dextromethorphan treatment significantly reduced severe ischemic neuronal damage (10.5% vs. 49.6%).
- Areas of cortical edema were significantly smaller in dextromethorphan-treated rabbits (10.2% vs. 38.6%).
- Neurophysiological recovery, measured by SEPs, was significantly faster in the dextromethorphan group.
Conclusions:
- Dextromethorphan demonstrated significant neuroprotective effects in a rabbit model of focal cerebral ischemia.
- The drug reduced ischemic neuronal damage and cerebral edema.
- Dextromethorphan promoted faster neurophysiological recovery, suggesting potential therapeutic value for stroke treatment.