Rapamycin attenuates aggressive behavior in a rat model of pilocarpine-induced epilepsy

Huang, Xiaoxing; McMahon, John J.; Huang, Yunfei

doi:10.1016/j.neuroscience.2012.04.011

Cited by 41 publications

(40 citation statements)

References 44 publications

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“…In the present study, we demonstrated that the upregulation of P75NTR and pro-NGF is associated with behavioral alterations following the induction of SE by pilocarpine, which is consistent with previous studies [35,36] . It has been shown that neurotrophin receptors, especially P75NTR, play an important role in epileptogenesis and are up-regulated in the animal model of epilepsy and epileptic patients [65,66] .…”

Section: Discussionsupporting

confidence: 93%

“…Excitability and sensory responsiveness of control and pilocarpine-treated rats were evaluated using different behavioral tests, including approach-response, touch-response, finger-snap, and pick-up tests as described by Huang et al [35] . Behavioral assessments were performed two weeks after status epilepticus induction between 9 a.m. and 12.30 p.m. Three groups of epileptic rats were randomly selected for i.p.…”

Section: Behavioral Assessmentmentioning

confidence: 99%

“…Responses were recorded as 1, the rat has no reaction; 2, the rat turned toward the object; 3, the rat moved away from the object; 4, the rat frozen; 5, the rat turned toward the touch; 6, the rat turned away from the touch; 7, the rat jumped with or without vocalizations [35,37] .…”

Section: Touch-response Testmentioning

confidence: 99%

“…Responses were scored as 1, the rat had no reaction; 2, the rat jumped slightly (normal reaction); 3, the rat jumped suddenly [35,38] .…”

Section: Finger-snap Testmentioning

confidence: 99%

“…Responses were scored as 1, very easy; 2, easy with vocalizations; 3, some difficulties, the rat reared and faced the hand; 4, frozen (the rat); 5, difficult, the rat avoided the hand by moving away; 6, very difficult, the rat behaved defensively and may attacked the hand [35,37] . The behavioral tests were done by three independent observers, and the means of their scores were calculated for each animal for each test.…”

Section: Pick-up Testmentioning

confidence: 99%

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Blockade of p75 Neurotrophin Receptor Reverses Irritability and Anxiety-Related Behaviors in a Rat Model of Status Epilepticus

Mehrabi

Janahamdi

Joghataie

et al. 2018

IBJ

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Background: Many recent epidemiological studies have shown that epileptic patients are more likely suffer from depression, anxiety, and irritability. However, the cellular mechanisms of epilepsy-induced psychotic behaviors are not fully elucidated. Neurotrophin receptors have been suggested to be involved in epilepsy and also in psychiatric disorders. Up-regulation of p75NTR expression and activation of p75NTR signalling cascades after the seizure have been shown, but the role of the p75 receptor in epilepsy-induced psychotic behaviors has not been documented so far. Therefore, the present work aimed to investigate the effect of p75 receptor blockade on seizure activity, irritability, and anxiety-like behaviors in a rat model of status epilepticus. Methods: Rats were injected with pilocarpine (350 mg/ kg, i.p.) to induce status epilepticus. Then various behavioral tests were performed after the blockade of p75NTR alone or in combination with p75 antagonist and phenobarbital. Molecular analysis by PCR was performed to investigate the expression of p75 and pro-NGF. Results: Molecular findings indicated a high level of mRNA expression for both p75 receptors and pro-NGF in the epileptic model group. Results also showed that the administration of p75 antagonist alone or in combination with phenobarbital was able to significantly influence the behavioral responses. Furthermore, 20-hours video monitoring showed a decrease in the frequency and duration of seizures in the rat group receiving p75 antagonist. Conclusion: Taken together, the present study suggests that the blockade of the p75 receptor may affect the irritability and anxietyrelated behavior in a rat model of status epilepticus.

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Section: Discussionsupporting

confidence: 93%

Section: Behavioral Assessmentmentioning

confidence: 99%

Section: Touch-response Testmentioning

confidence: 99%

“…Responses were scored as 1, the rat had no reaction; 2, the rat jumped slightly (normal reaction); 3, the rat jumped suddenly [35,38] .…”

Section: Finger-snap Testmentioning

confidence: 99%

Section: Pick-up Testmentioning

confidence: 99%

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Blockade of p75 Neurotrophin Receptor Reverses Irritability and Anxiety-Related Behaviors in a Rat Model of Status Epilepticus

Mehrabi

Janahamdi

Joghataie

et al. 2018

IBJ

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Everolimus treatment of refractory epilepsy in tuberous sclerosis complex

Krueger

Wilfong

Holland‐Bouley

et al. 2013

Annals of Neurology

346

253

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Objective: Epilepsy is a major manifestation of tuberous sclerosis complex (TSC). Everolimus is an mammalian target of rapamycin complex 1 inhibitor with demonstrated benefit in several aspects of TSC. We report the first prospective human clinical trial to directly assess whether everolimus will also benefit epilepsy in TSC patients. Methods: The effect of everolimus on seizure control was assessed using a prospective, multicenter, open-label, phase I/II clinical trial. Patients 2 years of age with confirmed diagnosis of TSC and medically refractory epilepsy were treated for a total of 12 weeks. The primary endpoint was percentage of patients with a 50% reduction in seizure frequency over a 4-week period before and after treatment. Secondary endpoints assessed impact on electroencephalography (EEG), behavior, and quality of life. Results: Twenty-three patients were enrolled, and 20 patients were treated with everolimus. Seizure frequency was reduced by 50% in 12 of 20 subjects. Overall, seizures were reduced in 17 of the 20 by a median reduction of 73% (p < 0.001). Seizure frequency was also reduced during 23-hour EEG monitoring (p 5 0.007). Significant reductions in seizure duration and improvement in parent-reported behavior and quality of life were also observed. There were 83 reported adverse events that were thought to be treatment-related, all of which were mild or moderate in severity. Interpretation: Seizure control improved in the majority of TSC patients with medically refractory epilepsy following treatment with everolimus. Everolimus demonstrated additional benefits on behavior and quality of life. Treatment was safe and well tolerated. Everolimus may be a therapeutic option for refractory epilepsy in this population.

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