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Published on: May 15, 2018
Postictal in situ MRS brain lactate in the rat kindling model
Objective:
To determine the temporal and spatial extent of the lactate (Lact) changes as correlated with seizure characteristics and EEG changes in the rat kindling model.
Background:
Prior studies using MRS have detected cerebral Lact postictally in animal models of seizures and in patients with intractable focal epilepsy.
Methods:
We performed MRS in sham control rats (n = 4) and in rats stimulated in the right hippocampus at two different stages of the kindling and at three time points after the seizures: <2 hours (n = 8 and 5, stage 0 and stage 5), 2 to 3 hours (n = 5 and 6), and >3 hours (n = 4 and 2). Lact/creatine (Cr) and N-acetylaspartate (NAA)/Cr ratios were measured in six contiguous voxels (three left, three right) covering the hippocampi, anterior and posterior regions, and compared with EEG and ictal behavior. Lact/Cr ratios were measured at a very low level in the sham control rats and in the >3-hour group.
Results:
In the <2-hour group, Lact/Cr increase was higher in stage-5 rats as compared with stage-0 rats (p = 0.001, unpaired t-test) and sham control rats when all the voxels were considered. Lact/Cr ratios were higher in the stimulated area as compared with all other brain areas in stage-0 rats (p = 0.05, paired t-test) but not in the stage-5 rats. Similar results with more inter-animal variability were measured in the 2- to 3-hour group. NAA/Cr ratios increased significantly after stage-0 kindling in the stimulated hippocampus but not after stage-5 kindling.
Conclusions:
Postictal Lact increase as assayed by MRS correlates with EEG and behavioral seizures and suggests that it would be an additional noninvasive technique for seizure localization during the presurgical evaluation of patients with intractable focal epilepsy.
Insights
Postictal increases in lactate (Lact) levels correlate with seizure activity in a rat model. Magnetic Resonance Spectroscopy (MRS) shows potential as a noninvasive tool for localizing seizures in epilepsy patients.
Area of Science:
- Neuroscience
- Biochemistry
- Medical Imaging
Background:
- Cerebral lactate elevations post-seizure have been observed using Magnetic Resonance Spectroscopy (MRS) in animal models and human epilepsy.
- Understanding the temporal and spatial dynamics of these lactate changes is crucial for seizure characterization.
Purpose of the Study:
- To investigate the temporal and spatial extent of lactate (Lact) changes in relation to seizure characteristics and EEG changes within the rat kindling model.
- To assess the correlation between postictal lactate levels and seizure severity and localization.
Main Methods:
- Magnetic Resonance Spectroscopy (MRS) was employed in sham control rats and kindled rats at different seizure stages (stage 0 and stage 5).
- Lactate/creatine (Lact/Cr) and N-acetylaspartate/creatine (NAA/Cr) ratios were measured in multiple hippocampal voxels at varying time points (<2 hours, 2-3 hours, >3 hours) post-seizure.
- Measurements were correlated with electroencephalography (EEG) and observed ictal behavior.
Main Results:
- Postictal Lact/Cr ratios were significantly elevated in stage-5 kindled rats compared to stage-0 rats and sham controls within 2 hours post-seizure.
- In stage-0 rats, Lact/Cr was higher in the stimulated hippocampus, but this spatial localization was lost in stage-5 rats.
- NAA/Cr ratios increased after stage-0 kindling but not after stage-5 kindling in the stimulated hippocampus.
Conclusions:
- Postictal increases in lactate, detected by MRS, correlate with EEG and behavioral seizure manifestations.
- MRS shows promise as an additional noninvasive technique for seizure localization in the presurgical evaluation of patients with intractable focal epilepsy.
