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Unilateral Hypothalamus Inactivation Prevents PTZ Kindling Development through Hippocampal Orexin Receptor 1 Modulation
INTRODUCTION: Epilepsy is a neural disorder in which abnormal plastic changes during short and long term periods lead to increased excitability of brain tissue. Kindling is an animal model of epileptogenesis which results in changes of synaptic plasticity due to repetitive electrical or chemical sub...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Iranian Neuroscience Society
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4202604/ https://www.ncbi.nlm.nih.gov/pubmed/25436086 |
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author | Akbari, Nasibe Salmani, Mahmoud Elahdadi Goudarzvand, Mahdi LashkarBoluki, Taghi Goudarzi, Iran Abrari, Kataneh |
author_facet | Akbari, Nasibe Salmani, Mahmoud Elahdadi Goudarzvand, Mahdi LashkarBoluki, Taghi Goudarzi, Iran Abrari, Kataneh |
author_sort | Akbari, Nasibe |
collection | PubMed |
description | INTRODUCTION: Epilepsy is a neural disorder in which abnormal plastic changes during short and long term periods lead to increased excitability of brain tissue. Kindling is an animal model of epileptogenesis which results in changes of synaptic plasticity due to repetitive electrical or chemical sub-convulsive stimulations of the brain. Lateral hypothalamus, as the main niche of orexin neurons with extensive projections, is involved in sleep and wakefulness and so it affects the excitability of the brain. Therefore, we investigated whether lateral hypothalamic area (LHA) inactivation or orexin-A receptor blocking could change convulsive behavior of acute and kindled PTZ treated animals and if glutamate has a role in this regard. METHODS: Kindling was induced by 40 mg/kg PTZ, every 48 hours up to 13 injections to each rat. Three consecutive stages 4 or 5 of convulsive behavior were used to ensure kindling. Lidocaine was injected stereotaxically to inactivate LHA, unilaterally. SB334867 used for orexin receptor 1 (OX1R) blocking administered in CSF. RESULTS: We demonstrated that LHA inactivation prevented PTZ kindling and hence, excitability evolution. Hippocampal glutamate content was decreased due to LHA inactivation, OX1R antagonist infusion, lidocaine injection and kindled groups. In accordance, OX1R antagonist (SB334867) and lidocaine injection decreased PTZ single dose induced convulsive behavior. While orexin-A i.c.v. infusion increased hippocampal glutamate content, it did not change PTZ induced convulsive intensity. DISCUSSION: It is concluded that LHA inactivation prevented kindling development probably through orexin receptor antagonism. CSF orexin probably acts as an inhibitory step on convulsive intensity through another unknown process. |
format | Online Article Text |
id | pubmed-4202604 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Iranian Neuroscience Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-42026042014-12-01 Unilateral Hypothalamus Inactivation Prevents PTZ Kindling Development through Hippocampal Orexin Receptor 1 Modulation Akbari, Nasibe Salmani, Mahmoud Elahdadi Goudarzvand, Mahdi LashkarBoluki, Taghi Goudarzi, Iran Abrari, Kataneh Basic Clin Neurosci Research Papers INTRODUCTION: Epilepsy is a neural disorder in which abnormal plastic changes during short and long term periods lead to increased excitability of brain tissue. Kindling is an animal model of epileptogenesis which results in changes of synaptic plasticity due to repetitive electrical or chemical sub-convulsive stimulations of the brain. Lateral hypothalamus, as the main niche of orexin neurons with extensive projections, is involved in sleep and wakefulness and so it affects the excitability of the brain. Therefore, we investigated whether lateral hypothalamic area (LHA) inactivation or orexin-A receptor blocking could change convulsive behavior of acute and kindled PTZ treated animals and if glutamate has a role in this regard. METHODS: Kindling was induced by 40 mg/kg PTZ, every 48 hours up to 13 injections to each rat. Three consecutive stages 4 or 5 of convulsive behavior were used to ensure kindling. Lidocaine was injected stereotaxically to inactivate LHA, unilaterally. SB334867 used for orexin receptor 1 (OX1R) blocking administered in CSF. RESULTS: We demonstrated that LHA inactivation prevented PTZ kindling and hence, excitability evolution. Hippocampal glutamate content was decreased due to LHA inactivation, OX1R antagonist infusion, lidocaine injection and kindled groups. In accordance, OX1R antagonist (SB334867) and lidocaine injection decreased PTZ single dose induced convulsive behavior. While orexin-A i.c.v. infusion increased hippocampal glutamate content, it did not change PTZ induced convulsive intensity. DISCUSSION: It is concluded that LHA inactivation prevented kindling development probably through orexin receptor antagonism. CSF orexin probably acts as an inhibitory step on convulsive intensity through another unknown process. Iranian Neuroscience Society 2014 /pmc/articles/PMC4202604/ /pubmed/25436086 Text en Copyright © 2014 Iranian Neuroscience Society http://creativecommons.org/licenses/by-nc/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly. |
spellingShingle | Research Papers Akbari, Nasibe Salmani, Mahmoud Elahdadi Goudarzvand, Mahdi LashkarBoluki, Taghi Goudarzi, Iran Abrari, Kataneh Unilateral Hypothalamus Inactivation Prevents PTZ Kindling Development through Hippocampal Orexin Receptor 1 Modulation |
title | Unilateral Hypothalamus Inactivation Prevents PTZ Kindling Development through Hippocampal Orexin Receptor 1 Modulation |
title_full | Unilateral Hypothalamus Inactivation Prevents PTZ Kindling Development through Hippocampal Orexin Receptor 1 Modulation |
title_fullStr | Unilateral Hypothalamus Inactivation Prevents PTZ Kindling Development through Hippocampal Orexin Receptor 1 Modulation |
title_full_unstemmed | Unilateral Hypothalamus Inactivation Prevents PTZ Kindling Development through Hippocampal Orexin Receptor 1 Modulation |
title_short | Unilateral Hypothalamus Inactivation Prevents PTZ Kindling Development through Hippocampal Orexin Receptor 1 Modulation |
title_sort | unilateral hypothalamus inactivation prevents ptz kindling development through hippocampal orexin receptor 1 modulation |
topic | Research Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4202604/ https://www.ncbi.nlm.nih.gov/pubmed/25436086 |
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