Comparative neuroanatomical and temporal characterization of FluoroJade-positive neurodegeneration after status epilepticus induced by systemic and intrahippocampal pilocarpine in Wistar rats

Abstract

The aims of this study were to characterize the spatial distribution of neurodegeneration after status epilepticus (SE) induced by either systemic (S) or intrahippocampal (H) injection of pilocarpine (PILO), two models of temporal lobe epilepsy (TLE), using FluoroJade (FJ) histochemistry, and to evaluate the kinetics of FJ staining in the H-PILO model. Therefore, we measured the severity of behavioral seizures during both types of SE and also evaluated the FJ staining pattern at 12, 24, and 168 h (7days) after the H-PILO insult. We found that the amount of FJ-positive (FJ+) area was greater in SE induced by S-PILO as compared to SE induced by H-PILO. After SE induced by H-PILO, we found more FJ+ cells in the hilus of the dentate gyrus (DG) at 12 h, in CA3 at 24 h, and in CA1 at 168 h. We found also no correlation between seizure severity and the number of FJ+ cells in the hippocampus. Co-localization studies of FJ+ cells with either neuronal-specific nuclear protein (NeuN) or glial fibrillary acidic protein (GFAP) labeling 24 h after H-PILO demonstrated spatially selective neurodegeneration. Double labeling with FJ and parvalbumin (PV) showed both FJ+/PV+ and FJ+/PV- cells in hippocampus and entorhinal cortex, among other areas. The current data indicate that FJ+ areas are differentially distributed in the two TLE models and that these areas are greater in the S-PILO than in the H-PILO model. There is also a selective kinetics of FJ+ cells in the hippocampus after SE induced by H-PILO, with no association with the severity of seizures, probably as a consequence of the extra-hippocampal damage. These data point to SE induced by H-PILO as a low-mortality model of TLE, with regional spatial and temporal patterns of FJ staining.

PI3Kγ deficiency enhances seizures severity and associated outcomes in a mouse model of convulsions induced by intrahippocampal injection of pilocarpine

“…Due to the high mortality induced by intraperitoneal injection of pilocarpine described in the literature (Curia et al, 2008), we have standardized the model of seizures induced by intrahippocampal injection of pilocarpine in mice, as previously demonstrated in rats (Castro et al, 2011;Furtado Mde et al, 2002). As shown in Table 1 (supplementary data), seventy-five percent of the animals developed SE with a bilateral injection of pilocarpine at the dose of 20 μg/site, albeit no mortality was observed.…”

The primate seahorse rhythm

“…The decrease in their cell number occurs in some cases of epilepsy (Castro et al, 2011;Dinocourt et al, 2003), Alzheimer's disease (Brady and Mufson, 1997;Takahashi et al, 2010), schizophrenia (Nullmeier et al, 2011;Zhang and Reynolds, 2002), and other disorders such as dementia with Lewis bodies (Bernstein et al, 2011). Although the rhythmicity anti-CR (C day period; D night period), and anti-PV (E day period; F night period).…”

Chemically-induced TLE models: Topical application

“…Pilocarpine has been shown to trigger acute and chronic seizures after intracerebroventricular and intrahippocampal administration (Croiset and De, 1992;Millan et al, 1993;Smolders et al, 1997;Lindekens et al, 2000;Furtado et al, 2002Furtado et al, , 2011Castro et al, 2011;Medina-Ceja et al, 2014). Detailed behavioral, electrophysiological and morphological analyses have been performed in mice by Furtado et al (2002Furtado et al ( , 2011.…”

“…Histopathological studies showed neurodegeneration in the hippocampal CA1, CA3 and hilus subfields, and mossy fiber sprouting in the inner molecular layer of the dentate gyrus. In a recent work, Castro et al (2011) compared neurodegeneration induced by systemic and intrahippocampal administration in rats. The authors found much less extra-hippocampal damage after focal, compared with systemic injection, although neurodegeneration in some cortical regions, the amygdala and thalamus was also observed after intrahippocampal injection.…”