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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 neuronal cell loss in the CA3 hippocampal region after status epilepticus (SE), in pilocarpine-treated rats.Neurons were identified by the anti-neuron-specific nuclear protein (NeuN) antibody, as shown in the control staining. NeuN-immunopositive cells were markedly decreased in pilocarpine-treated rats of the saline group, sacrificed 4 days after SE. This phenomenon was attenuated by treatment with GH secretagogues. ## = P<0.01 vs the control non-epileptic group, Fisher's LSD test. Scale bar, 150 µm.
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pone-0072716-g008: Photomicrographs illustrating neuronal cell loss in the CA3 hippocampal region after status epilepticus (SE), in pilocarpine-treated rats.Neurons were identified by the anti-neuron-specific nuclear protein (NeuN) antibody, as shown in the control staining. NeuN-immunopositive cells were markedly decreased in pilocarpine-treated rats of the saline group, sacrificed 4 days after SE. This phenomenon was attenuated by treatment with GH secretagogues. ## = P<0.01 vs the control non-epileptic group, Fisher's LSD test. Scale bar, 150 µm.

Mentions: A different scenario emerged from the analysis of neuronal cell densities in the hippocampus proper. The highly packed distribution of neurons in the CA1 and CA3 regions did not allow a similar analysis to the one performed in the hilus of dentate gyrus and medial entorhinal cortex layer III. Thus, we sampled at higher magnification the CA1 sector proximal to the subiculum (Figure 7) and the CA3b sector (Figure 8), which represent for each respective region the most sensitive areas to damage in rat exposed to SE [27], [31]. In CA1, we found that NeuN-positive cells were decreased in the saline group to approximately 65% of control levels (P<0.01). A similar decrease was observed in GHS-R1a agonist-treated rats: NeuN-positive cells were decreased, respectively, to 77% in ghrelin (P<0.05 vs controls) and to 67% of control levels in JMV-1843 (P<0.01) groups. Contrary to what we observed in the hilus and entorhinal cortex, JMV-1843 did not have any protective effect in the CA1.


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 neuronal cell loss in the CA3 hippocampal region after status epilepticus (SE), in pilocarpine-treated rats.Neurons were identified by the anti-neuron-specific nuclear protein (NeuN) antibody, as shown in the control staining. NeuN-immunopositive cells were markedly decreased in pilocarpine-treated rats of the saline group, sacrificed 4 days after SE. This phenomenon was attenuated by treatment with GH secretagogues. ## = P<0.01 vs the control non-epileptic group, Fisher's LSD test. Scale bar, 150 µm.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0072716-g008: Photomicrographs illustrating neuronal cell loss in the CA3 hippocampal region after status epilepticus (SE), in pilocarpine-treated rats.Neurons were identified by the anti-neuron-specific nuclear protein (NeuN) antibody, as shown in the control staining. NeuN-immunopositive cells were markedly decreased in pilocarpine-treated rats of the saline group, sacrificed 4 days after SE. This phenomenon was attenuated by treatment with GH secretagogues. ## = P<0.01 vs the control non-epileptic group, Fisher's LSD test. Scale bar, 150 µm.
Mentions: A different scenario emerged from the analysis of neuronal cell densities in the hippocampus proper. The highly packed distribution of neurons in the CA1 and CA3 regions did not allow a similar analysis to the one performed in the hilus of dentate gyrus and medial entorhinal cortex layer III. Thus, we sampled at higher magnification the CA1 sector proximal to the subiculum (Figure 7) and the CA3b sector (Figure 8), which represent for each respective region the most sensitive areas to damage in rat exposed to SE [27], [31]. In CA1, we found that NeuN-positive cells were decreased in the saline group to approximately 65% of control levels (P<0.01). A similar decrease was observed in GHS-R1a agonist-treated rats: NeuN-positive cells were decreased, respectively, to 77% in ghrelin (P<0.05 vs controls) and to 67% of control levels in JMV-1843 (P<0.01) groups. Contrary to what we observed in the hilus and entorhinal cortex, JMV-1843 did not have any protective effect in the CA1.

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