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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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Changes in endothelin-1 (ET-1) immunoreactivity in the CA3 region of pilocarpine-treated rats after status epilepticus (SE).ET-1 is barely detectable in control non-epileptic rats (A). Immunoreactivity for ET-1 was strongly induced by the pilocarpine injection (B, illustrating a saline-treated rat), and ghrelin did not affect the remarkable induction of ET-1 (C). On the contrary, JMV-1843 counteracted the induction of ET-1 in the CA3 pyramidal cell layer (D, E). * = P<0.05 vs both saline and ghrelin groups, Fisher's LSD test. Scale bar, 150 µm.
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pone-0072716-g004: Changes in endothelin-1 (ET-1) immunoreactivity in the CA3 region of pilocarpine-treated rats after status epilepticus (SE).ET-1 is barely detectable in control non-epileptic rats (A). Immunoreactivity for ET-1 was strongly induced by the pilocarpine injection (B, illustrating a saline-treated rat), and ghrelin did not affect the remarkable induction of ET-1 (C). On the contrary, JMV-1843 counteracted the induction of ET-1 in the CA3 pyramidal cell layer (D, E). * = P<0.05 vs both saline and ghrelin groups, Fisher's LSD test. Scale bar, 150 µm.

Mentions: In view of the remarkable upregulation of laminin immunoreactivity found after intracerebral injection of ET-1 [31] and of the induction of this vasoactive neuropeptide after pilocarpine-induced SE [33], we analyzed the effects of pilocarpine and the GHS-R1a agonists on ET-1 immunoreactivity in CA3. ET-1 immunopositivity was barely detectable in control non-epileptic rats (Figure 4A). However, a prominent upregulation was observed in consequence of pilocarpine-induced SE (Figure 4B). This change was particularly evident in CA3 pyramidal neurons. Ghrelin administration did not modify the increase of ET-1 immunoreactivity (Figure 4C). On the contrary, JMV-1843 significantly counteracted the increase of ET-1 immunoreactivity in pilocarpine-treated rats (P<0.05 vs saline and ghrelin groups; Figure 4D,E).


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)

Changes in endothelin-1 (ET-1) immunoreactivity in the CA3 region of pilocarpine-treated rats after status epilepticus (SE).ET-1 is barely detectable in control non-epileptic rats (A). Immunoreactivity for ET-1 was strongly induced by the pilocarpine injection (B, illustrating a saline-treated rat), and ghrelin did not affect the remarkable induction of ET-1 (C). On the contrary, JMV-1843 counteracted the induction of ET-1 in the CA3 pyramidal cell layer (D, E). * = P<0.05 vs both saline and ghrelin groups, Fisher's LSD test. Scale bar, 150 µm.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3755992&req=5

pone-0072716-g004: Changes in endothelin-1 (ET-1) immunoreactivity in the CA3 region of pilocarpine-treated rats after status epilepticus (SE).ET-1 is barely detectable in control non-epileptic rats (A). Immunoreactivity for ET-1 was strongly induced by the pilocarpine injection (B, illustrating a saline-treated rat), and ghrelin did not affect the remarkable induction of ET-1 (C). On the contrary, JMV-1843 counteracted the induction of ET-1 in the CA3 pyramidal cell layer (D, E). * = P<0.05 vs both saline and ghrelin groups, Fisher's LSD test. Scale bar, 150 µm.
Mentions: In view of the remarkable upregulation of laminin immunoreactivity found after intracerebral injection of ET-1 [31] and of the induction of this vasoactive neuropeptide after pilocarpine-induced SE [33], we analyzed the effects of pilocarpine and the GHS-R1a agonists on ET-1 immunoreactivity in CA3. ET-1 immunopositivity was barely detectable in control non-epileptic rats (Figure 4A). However, a prominent upregulation was observed in consequence of pilocarpine-induced SE (Figure 4B). This change was particularly evident in CA3 pyramidal neurons. Ghrelin administration did not modify the increase of ET-1 immunoreactivity (Figure 4C). On the contrary, JMV-1843 significantly counteracted the increase of ET-1 immunoreactivity in pilocarpine-treated rats (P<0.05 vs saline and ghrelin groups; Figure 4D,E).

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