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Protective but not anticonvulsant effects of ghrelin and JMV-1843 in the pilocarpine model of Status epilepticus.

Lucchi C, Curia G, Vinet J, Gualtieri F, Bresciani E, Locatelli V, Torsello A, Biagini G - PLoS ONE (2013)

Bottom Line: In saline group the area of lesion, characterized by lack of glial fibrillary acidic protein immunoreactivity, was of 0.45 ± 0.07 mm(2) in the hippocampal stratum lacunosum-moleculare, and was accompanied by upregulation of laminin immunostaining, and by increased endothelin-1 expression.In addition, JMV-1843 counteracted (P<0.05) the changes in laminin and endothelin-1 expression, both increased in ghrelin-treated rats.These results demonstrate diverse protective effects of growth hormone secretagogues in rats exposed to status epilepticus.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.

ABSTRACT
In models of status epilepticus ghrelin displays neuroprotective effects mediated by the growth hormone secretagogue-receptor 1a (GHS-R1a). This activity may be explained by anticonvulsant properties that, however, are controversial. We further investigated neuroprotection and the effects on seizures by comparing ghrelin with a more effective GHS-R1a agonist, JMV-1843. Rats were treated either with ghrelin, JMV-1843 or saline 10 min before pilocarpine, which was used to induce status epilepticus. Status epilepticus, developed in all rats, was attenuated by diazepam. No differences were observed among the various groups in the characteristics of pilocarpine-induced seizures. In saline group the area of lesion, characterized by lack of glial fibrillary acidic protein immunoreactivity, was of 0.45 ± 0.07 mm(2) in the hippocampal stratum lacunosum-moleculare, and was accompanied by upregulation of laminin immunostaining, and by increased endothelin-1 expression. Both ghrelin (P<0.05) and JMV-1843 (P<0.01) were able to reduce the area of loss in glial fibrillary acidic protein immunostaining. In addition, JMV-1843 counteracted (P<0.05) the changes in laminin and endothelin-1 expression, both increased in ghrelin-treated rats. JMV-1843 was able to ameliorate neuronal survival in the hilus of dentate gyrus and medial entorhinal cortex layer III (P<0.05 vs saline and ghrelin groups). These results demonstrate diverse protective effects of growth hormone secretagogues in rats exposed to status epilepticus.

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Photomicrographs illustrating the lesion appearing in the hilus of dentate gyrus after status epilepticus (SE), in pilocarpine-treated rats.The lesion was investigated using the Fluoro-Jade B staining in saline (A), ghrelin (B) and JMV-1843 (C) groups. JMV-1843 administration decreased the number of Fluoro-Jade B-positive cells (D).* = P<0.05 vs both saline and ghrelin groups, Fisher's LSD test. Scale bar, 100 µm.
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pone-0072716-g009: Photomicrographs illustrating the lesion appearing in the hilus of dentate gyrus after status epilepticus (SE), in pilocarpine-treated rats.The lesion was investigated using the Fluoro-Jade B staining in saline (A), ghrelin (B) and JMV-1843 (C) groups. JMV-1843 administration decreased the number of Fluoro-Jade B-positive cells (D).* = P<0.05 vs both saline and ghrelin groups, Fisher's LSD test. Scale bar, 100 µm.

Mentions: NeuN has been used often as a specific marker of neuronal cell loss and it provided coherent results both in pilocarpine [45] and in kainate models [46]. However, caution must be used when assuming changes in NeuN immunoreactivity as a direct index of neuronal cell loss [38]. Thus, we evaluated damaged cells by Fluoro-Jade B, a consistent marker of cell death [40]. No stained cells were observed in control animals (data not shown). In contrast, positively stained cells were always observed in pilocarpine rats treated with either saline or GHS-R1a agonists. In general, findings obtained with the Fluoro-Jade B staining confirmed results obtained with NeuN immunoreactivity. More precisely, in the hilus (Figure 9), JMV-1843-treated animals displayed approximately 35% less fluorescent cells compared to saline- or ghrelin-treated rats (P<0.05). A similar scenario was found also in the medial entorhinal cortex, layer III (Figure 10), where the level of fluorescent cells in the JMV-1843 group was significantly lower (approximately −30%) in comparison with that of the saline (P<0.01) and ghrelin (P<0.05) groups.


Protective but not anticonvulsant effects of ghrelin and JMV-1843 in the pilocarpine model of Status epilepticus.

Lucchi C, Curia G, Vinet J, Gualtieri F, Bresciani E, Locatelli V, Torsello A, Biagini G - PLoS ONE (2013)

Photomicrographs illustrating the lesion appearing in the hilus of dentate gyrus after status epilepticus (SE), in pilocarpine-treated rats.The lesion was investigated using the Fluoro-Jade B staining in saline (A), ghrelin (B) and JMV-1843 (C) groups. JMV-1843 administration decreased the number of Fluoro-Jade B-positive cells (D).* = P<0.05 vs both saline and ghrelin groups, Fisher's LSD test. Scale bar, 100 µm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3755992&req=5

pone-0072716-g009: Photomicrographs illustrating the lesion appearing in the hilus of dentate gyrus after status epilepticus (SE), in pilocarpine-treated rats.The lesion was investigated using the Fluoro-Jade B staining in saline (A), ghrelin (B) and JMV-1843 (C) groups. JMV-1843 administration decreased the number of Fluoro-Jade B-positive cells (D).* = P<0.05 vs both saline and ghrelin groups, Fisher's LSD test. Scale bar, 100 µm.
Mentions: NeuN has been used often as a specific marker of neuronal cell loss and it provided coherent results both in pilocarpine [45] and in kainate models [46]. However, caution must be used when assuming changes in NeuN immunoreactivity as a direct index of neuronal cell loss [38]. Thus, we evaluated damaged cells by Fluoro-Jade B, a consistent marker of cell death [40]. No stained cells were observed in control animals (data not shown). In contrast, positively stained cells were always observed in pilocarpine rats treated with either saline or GHS-R1a agonists. In general, findings obtained with the Fluoro-Jade B staining confirmed results obtained with NeuN immunoreactivity. More precisely, in the hilus (Figure 9), JMV-1843-treated animals displayed approximately 35% less fluorescent cells compared to saline- or ghrelin-treated rats (P<0.05). A similar scenario was found also in the medial entorhinal cortex, layer III (Figure 10), where the level of fluorescent cells in the JMV-1843 group was significantly lower (approximately −30%) in comparison with that of the saline (P<0.01) and ghrelin (P<0.05) groups.

Bottom Line: In saline group the area of lesion, characterized by lack of glial fibrillary acidic protein immunoreactivity, was of 0.45 ± 0.07 mm(2) in the hippocampal stratum lacunosum-moleculare, and was accompanied by upregulation of laminin immunostaining, and by increased endothelin-1 expression.In addition, JMV-1843 counteracted (P<0.05) the changes in laminin and endothelin-1 expression, both increased in ghrelin-treated rats.These results demonstrate diverse protective effects of growth hormone secretagogues in rats exposed to status epilepticus.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.

ABSTRACT
In models of status epilepticus ghrelin displays neuroprotective effects mediated by the growth hormone secretagogue-receptor 1a (GHS-R1a). This activity may be explained by anticonvulsant properties that, however, are controversial. We further investigated neuroprotection and the effects on seizures by comparing ghrelin with a more effective GHS-R1a agonist, JMV-1843. Rats were treated either with ghrelin, JMV-1843 or saline 10 min before pilocarpine, which was used to induce status epilepticus. Status epilepticus, developed in all rats, was attenuated by diazepam. No differences were observed among the various groups in the characteristics of pilocarpine-induced seizures. In saline group the area of lesion, characterized by lack of glial fibrillary acidic protein immunoreactivity, was of 0.45 ± 0.07 mm(2) in the hippocampal stratum lacunosum-moleculare, and was accompanied by upregulation of laminin immunostaining, and by increased endothelin-1 expression. Both ghrelin (P<0.05) and JMV-1843 (P<0.01) were able to reduce the area of loss in glial fibrillary acidic protein immunostaining. In addition, JMV-1843 counteracted (P<0.05) the changes in laminin and endothelin-1 expression, both increased in ghrelin-treated rats. JMV-1843 was able to ameliorate neuronal survival in the hilus of dentate gyrus and medial entorhinal cortex layer III (P<0.05 vs saline and ghrelin groups). These results demonstrate diverse protective effects of growth hormone secretagogues in rats exposed to status epilepticus.

Show MeSH
Related in: MedlinePlus