Abstracts

RATIONALE: The time course of neuronal loss following status epilepticus is unclear, and there has been no means of evaluating loss quantitatively in a nondestructive mannerso that the effect of therapy can be evaluated in vivo. In this study we use MR spectroscopic imaging of the neuronal marker N-acetyl aspartate (NAA) in rats following an episode of status epilepticus to define the time course of neuronal loss and to determine if appropriate early neuroprotective therapy can be demonstrated by this method.
METHODS: Status epilepticus was induced by 90 minutes of electrical stimulation of the midventral hippocampus in adult male Sprague-Dawley rats. There were 8 control animals and 6 to 7 animals per experimental group. The study was performed in a 4.7 Tesla, 9cm diameter small animal magnet. NAA levels (voxel size 7.9microliters) were determined bilaterally for the frontal cortex, amygdala/piriform cortex as well as the ventral hippocampus. The animals were scanned either at 1 day, 7 days or 56-60 days following status epilepticus. The spectroscopic findings were compared to the histology of the 7 day group using a semiquantitative scoring scale. A separate set was treated with 100mg/kg phenobarbital 1 hour after stimulation onset. These animals were scanned either 7 or 56-60 days later.
RESULTS: There were nonsignificant decreases in the NAA levels the day after stimulation, but there were significant decreases (p[lt]0.05) at seven days that correlated with histological damage scores in the 7 day group (p[lt]0.01). There was no further decrease, rather a slight increase, at 56 days, an increase that was related to the demonstrated tissue shrinkage in these chronic animals. The NAA levels in these chronic animals was significantly less than the levels in controls (p[lt]0.05) The phenobarbital treated rats had no decrease in the NAA levels at any time.
CONCLUSIONS: High resolution MR spectroscopy can define the time course of neuronal loss following status epilepticus and quantify the severity. Obtaining studies early following the injury (e.g. 1 day) may establish a reliable baseline value for subsequent comparison. The beneficial effects of therapy can also be demonstrated. This technique can provide a reliable nondestructive means for determining neuronal loss and the effects of therapy in vivo.
[Supported by: This study was supported in by by NINDS grant NS25605.
Objective: At the end of this presentation the participant will understand the potential utility of MR spectroscopy in monitoring neuronal loss and the effects of therapy.]