Cell damage and neurogenesis in the dentate granule cell layer of adult rats after pilocarpine- or kainate-induced status epilepticus

Abstract

Presented by A.C.M. PaivaDentate granule cells are generally considered to be relatively resistant to excitotoxicity and have been associated to robust synaptogenesis after neuronal damage. Synaptic reorganization of dentate granule cell axons, the mossy fibers, has been suggested to be relevant for hyperexcitability in human temporal lobe epilepsy and animal models. A recent hypothesis has suggested that mossy fiber sprouting is dependent on newly formed dentate granule cells. However, we have recently demonstrated that cycloheximide (CHX) can block the mossy fiber sprouting that would be otherwise induced by different epileptogenic agents and do not interfere with epileptogenesis in those models. Here, we investigated cell damage and neurogenesis in the dentate gyrus of pilocarpine-or kainate-treated animals with or without the co-administration of CHX. Dentate granule cells were highly vulnerable to pilocarpine induced-status epilepticus (SE), but hardly damaged by kainate induced-SE. CHX-pretreatment markedly reduced the number of injured neurons after pilocarpine-induced SE. Induction of SE dramatically increased the mitotic rate of KA and KA + CHX treated animals. Induction of SE in animals injected with pilocarpine alone led to increases of between two to sevenfold in the mitotic rate of dentate granule cells as compared to increases of between five and thirtyfold for pilocarpine+CHX animals. These observations indicate that in presence of cycloheximide the increase of the mitotic rate after pilocarpine-induced SE may be due to protection of a vulnerable precursor cell population that would otherwise degenerate. We further suggest that the mossy fiber sprouting and neurogenesis of granule cells are not necessarily related events. - ( September 14, 1999 The α1-adrenoceptor antagonist indoramin was used in the rat vas deferens and aorta, against contractions induced by noradrenaline. Indoramin behaved as a competitive antagonist yielding pA 2 values of 7.38 ± 0.05 in rat vas deferens and 6.78 ± 0.14 in aorta. In the presence of cocaine (6µM), the potency (pA 2 ) of indoramin in antagonizing the contractions of the vas deferens to noradrenaline was increased to 8.72 ± 0.07 while its potency remained pratically unchanged in the aorta (6.69 ± 0.12).

Water maze experience and prenatal choline supplementation differentially promote long‐term hippocampal recovery from seizures in adulthood

“…Taken together, these data are also consistent with our observation that the dentate GCL remained relatively intact compared to other cellular subfields in the hippocampus of KA-treated rats (Fig. 3), and in line with previous reports showing that dentate granule cells appear to be more resistant than other hippocampal neurons to KA-induced SE (Covolan et al, 2000; Hattiangady et al, 2004). …”

“…KA-induced SE led to moderate to considerable cell loss and disruption of cellular architecture in CA1, CA3, and the hilus of both CON and SUP rats, which can be seen in Figure 3. In contrast, there was mild to no cell loss in the GCL of the dentate gyrus, which is consistent with previous reports using the KA model of SE (Covolan et al, 2000). We used total hippocampal volume estimates to quantify hippocampal cell loss.…”

Potential role for ligand-gated ion channels after seizure-induced neurogenesis

“…Similar increases have been demonstrated in other rodent models of seizures, such as those induced by amygdala kindling [16] and by electroconvulsive shock [17]. Status epilepticus elicited in rats by administration of chemoconvulsants such as pilocarpine, kainic acid or pentylenetetrazole also increases neurogenesis [18,19]. A recent study shows that hippocampal neurogenesis is also stimulated after early-life febrile seizures induced by exposing young rat pups to a hyperthermia treatment [20,21].…”

Differential neurogenesis in the adult rat dentate gyrus: an identifiable zone that consistently lacks neurogenesis

“…Of particular interest in the current context are two recent studies using different experimentally induced forms of damage. Covolan et al (2000) reported an increase in the number of BrdU + cells in sections that would contain the NQZ (in sections 2.45 mm posterior to Bregma) after kainate-and pilocarpine-induced seizures. Conversely, Choi et al (2003), using a transient forebrain ischaemia model, found that the number of BrdU + cells increased in all sectors of the dentate gyrus, except the rostral suprapyramidal blade.…”