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Unilateral Hypothalamus Inactivation Prevents PTZ Kindling Development through Hippocampal Orexin Receptor 1 Modulation.

Akbari N, Salmani ME, Goudarzvand M, LashkarBoluki T, Goudarzi I, Abrari K - Basic Clin Neurosci (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: School of Biology, Damghan University, Damghan, Iran.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Orexin receptor (OX1R) modulation reduced convulsive intensity and altered hippocampal glutamate content. Single dose i.c.v infusion of OX1R antagonist (SB334867) (P < 0.01) and also single dose lidocaine administration (in LHA) (P < 0.05) reduced convulsive intensity (A). Orexin-A i.c.v infusion, increased (P < 0.05) hippocampal glutamate content, while blocking OX1R (SB334867) (P < 0.01) decreased that content compared to control.* P < 0.05; ** P < 0.01; PTZ, Pentylenetetrazol; Ctrl, Control; SB, SB334867; ORX, Orexin-A; Lido., lidocaine
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Figure 0002: Orexin receptor (OX1R) modulation reduced convulsive intensity and altered hippocampal glutamate content. Single dose i.c.v infusion of OX1R antagonist (SB334867) (P < 0.01) and also single dose lidocaine administration (in LHA) (P < 0.05) reduced convulsive intensity (A). Orexin-A i.c.v infusion, increased (P < 0.05) hippocampal glutamate content, while blocking OX1R (SB334867) (P < 0.01) decreased that content compared to control.* P < 0.05; ** P < 0.01; PTZ, Pentylenetetrazol; Ctrl, Control; SB, SB334867; ORX, Orexin-A; Lido., lidocaine

Mentions: PTZ (45 mg/kg) induced tonic clonic convulsions in over 90% of naïve animals. Comparing single dose PTZ induced convulsion scores using Kruskal Wallis one way analysis of variance showed a significant difference between groups (H(3) = 11.110, P < 0.01). Administration of orexin-A (i.c.v.) before PTZ injection, did not change seizure intensity and convulsive stage, significantly. Conversely, administration of OX1R antagonist, SB334867, reduced (Dunn‘s test, P < 0.05, Fig. 2-A, n = 8) seizure intensity prominently. Similar to lidocaine induced LHA inactivation in kindling paradigm, single dose lidocaine treatment of LHA decreased seizure intensity, too (Dunn‘s test, P < 0.01, Fig. 2-A, n = 8). This data showed that convulsive intensity is altered by orexinergic system modulation.


Unilateral Hypothalamus Inactivation Prevents PTZ Kindling Development through Hippocampal Orexin Receptor 1 Modulation.

Akbari N, Salmani ME, Goudarzvand M, LashkarBoluki T, Goudarzi I, Abrari K - Basic Clin Neurosci (2014)

Orexin receptor (OX1R) modulation reduced convulsive intensity and altered hippocampal glutamate content. Single dose i.c.v infusion of OX1R antagonist (SB334867) (P < 0.01) and also single dose lidocaine administration (in LHA) (P < 0.05) reduced convulsive intensity (A). Orexin-A i.c.v infusion, increased (P < 0.05) hippocampal glutamate content, while blocking OX1R (SB334867) (P < 0.01) decreased that content compared to control.* P < 0.05; ** P < 0.01; PTZ, Pentylenetetrazol; Ctrl, Control; SB, SB334867; ORX, Orexin-A; Lido., lidocaine
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4202604&req=5

Figure 0002: Orexin receptor (OX1R) modulation reduced convulsive intensity and altered hippocampal glutamate content. Single dose i.c.v infusion of OX1R antagonist (SB334867) (P < 0.01) and also single dose lidocaine administration (in LHA) (P < 0.05) reduced convulsive intensity (A). Orexin-A i.c.v infusion, increased (P < 0.05) hippocampal glutamate content, while blocking OX1R (SB334867) (P < 0.01) decreased that content compared to control.* P < 0.05; ** P < 0.01; PTZ, Pentylenetetrazol; Ctrl, Control; SB, SB334867; ORX, Orexin-A; Lido., lidocaine
Mentions: PTZ (45 mg/kg) induced tonic clonic convulsions in over 90% of naïve animals. Comparing single dose PTZ induced convulsion scores using Kruskal Wallis one way analysis of variance showed a significant difference between groups (H(3) = 11.110, P < 0.01). Administration of orexin-A (i.c.v.) before PTZ injection, did not change seizure intensity and convulsive stage, significantly. Conversely, administration of OX1R antagonist, SB334867, reduced (Dunn‘s test, P < 0.05, Fig. 2-A, n = 8) seizure intensity prominently. Similar to lidocaine induced LHA inactivation in kindling paradigm, single dose lidocaine treatment of LHA decreased seizure intensity, too (Dunn‘s test, P < 0.01, Fig. 2-A, n = 8). This data showed that convulsive intensity is altered by orexinergic system modulation.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: School of Biology, Damghan University, Damghan, Iran.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus