Manganese-enhanced magnetic resonance imaging in the acute phase of the pilocarpine-induced model of epilepsy

Abstract

Magnetic resonance images are useful in the study of experimental models of temporal lobe epilepsy. The manganese-enhanced MRI (MEMRI) technique is of interest since it combines the effects caused by manganese on the increased contrast in activated cell populations, when competing with calcium in synaptic transmission. Thus, the purpose of this study was to investigate the temporal evolution of the contrast related to manganese in the acute phase of temporal lobe epilepsy induced by systemic pilocarpine and compare it to the expression of the c-Fos protein. During this phase, the intensity of the MEMRI signal was analyzed at three different time points (5, 15 or 30 minutes) after the onset of status epilepticus (SE). The group that was maintained in status epilepticus for 30 minutes showed a decrease in intensity of the signal in CA1 and the dentate gyrus (DG). There were no differences between the control group and the other groups treated with pilocarpine. The expression of the protein, c-Fos, in the same animals showed that even in the short-duration status epilepticus (5 minutes), there was already maximal cellular activation in subregions of the hippocampus (DG, CA1 and CA3). Under the experimental conditions tested, our data suggest that the MEMRI signal was not sensitive for the identification of detectable variations of cell activation in the acute phase of the pilocarpine model. Our findings are not consistent with the idea that manganese contrast reflects primarily alterations in cellular activity during SE when other signal-modifying elements can act.

Reduced hippocampal manganese-enhanced MRI (MEMRI) signal during pilocarpine-induced status epilepticus: Edema or apoptosis?

“…The MEMRI and c-fos expression data presented here are consistent with our own and others' previous data, which showed decrease in relative signal intensity in T 1 -weighted MEMRI images in the hippocampus during pilocarpine and kainate SE (Alvestad et al, 2007;Immonen et al, 2008;Malheiros et al, 2012a). There are no identified MEMRI differences between pilocarpine-treated animals (SE5 and SE15) and controls for the dentate gyrus (DG), CA1 (Cornu Ammonis) and CA3 fields.…”

“…These groups were not MnCl 2 injected, and T 2 -weighted MRI was acquired to compare their aquaporin-4 expression. For Groups 1 and 2 we used exactly the same protocols as previously published (Malheiros et al, 2012a).…”

“…In an attempt to circumvent the possible causes of reduction in the MEMRI signal during SE (cell damage/loss), the status was fully blocked at progressive time periods after its onset (5, 15 or 30 min) and the cell activity and the MEMRI signal were evaluated. It resulted that short durations of status did not produce differences in the MEMRI signal (30 min of SE reduced MEMRI signal) despite increased c-fos expression (Malheiros et al, 2012a).…”

Manganese-Enhanced MRI: Biological Applications in Neuroscience

“…A possible explanation for this finding is that the MEMRI signal may have been obscured by cell damage that occurs at this early phase, especially when SE lasts more than 30 min. Similar results have been shown during the acute phase of the pilocarpine model ( 35 , 109 ), even when SE lasted only from 5 to 30 min (Figure 1 ). A proposed mechanism to explain this finding is that reductions in MEMRI signal could be related to hippocampal cell edema rather than apoptotic cell death ( 35 ).…”

Long-Term Effects of Anterior Thalamic Nucleus Deep Brain Stimulation on Spatial Learning in the Pilocarpine Model of Temporal Lobe Epilepsy

“…This dose was sufficient to induce tonic‐clonic seizures within 20 min, culminating in SE up to 40 min after pilocarpine administration. SE was characterized by the presence of uninterrupted behavioral seizures for at least 5 min . At SE onset, rats were randomly assigned to receive DBS either during SE only ( n = 38, PDBSa group) or during SE + the silent phase ( n = 38, PDBSs group).…”