Anticonvulsant effect of neural regeneration peptide 2945 on pentylenetetrazol-induced seizures in rats

Sajadian, Azadeh; Esteghamat, Sana; Karimzadeh, Fariba; Eshaghabadi, Arezou; Sieg, Frank; Speckmann, Erwin‐Josef; Meuth, Sven G.; Seidenbecher, Thomas; Budde, Thomas; Gorji, Ali

doi:10.1016/j.npep.2014.11.002

Cited by 16 publications

(8 citation statements)

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“…Hence, ongoing studies focus on the hypothesis that the encephalitides with antibodies against intracellular antigens [e.g., glutamic acid decarboxylase (GAD)] show neurodegeneration mediated by T cells, while encephalitides with antibodies against surface antigens [e.g., γ-amino butyric acid (GABA) receptor] are antibody mediated (Figure 1 ) ( 18 , 20 ). These findings indicate that substances increasing GABA signaling may prevent tissue damage and seizures ( 21 ).…”

Section: Role Of Neuronal Antigen-reactive Cd8 + Tmentioning

confidence: 92%

CD8+ T Cell-Mediated Neuronal Dysfunction and Degeneration in Limbic Encephalitis

et al. 2015

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Autoimmune inflammation of the limbic gray matter structures of the human brain has recently been identified as major cause of mesial temporal lobe epilepsy with interictal temporal epileptiform activity and slowing of the electroencephalogram, progressive memory disturbances, as well as a variety of other behavioral, emotional, and cognitive changes. Magnetic resonance imaging exhibits volume and signal changes of the amygdala and hippocampus, and specific anti-neuronal antibodies binding to either intracellular or plasma membrane neuronal antigens can be detected in serum and cerebrospinal fluid. While effects of plasma cell-derived antibodies on neuronal function and integrity are increasingly becoming characterized, potentially contributing effects of T cell-mediated immune mechanisms remain poorly understood. CD8+ T cells are known to directly interact with major histocompatibility complex class I-expressing neurons in an antigen-specific manner. Here, we summarize current knowledge on how such direct CD8+ T cell–neuron interactions may impact neuronal excitability, plasticity, and integrity on a single cell and network level and provide an overview on methods to further corroborate the in vivo relevance of these mechanisms mainly obtained from in vitro studies.

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Section: Role Of Neuronal Antigen-reactive Cd8 + Tmentioning

confidence: 92%

CD8+ T Cell-Mediated Neuronal Dysfunction and Degeneration in Limbic Encephalitis

et al. 2015

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“…This would lead to increased Egr1 transcription factor interaction at respective consensus binding sequences of the glutamate decarboxylase (GAD) promoter, provoking gene upregulation and subsequent de novo GABA production within minutes throughout thalamo-cortical circuits and other regions of the brain [30]. This biological action has been shown for NRP2945 by immunocytochemical analysis of GABA in various brain regions of rats treated acutely with PTZ [22]. That study also showed increased protein expression for GABA A receptor subunits alpha and beta that are constituents of the synaptic form of the GABA A receptor.…”

Section: Discussionmentioning

confidence: 99%

“…Most impressive was that the effects of chronic treatment were sustained for at least 10 days following conclusion of the treatment period, indicative of potent disease-modifying effects of NRP. This compound has also been shown to be efficacious against acute PTZ-induced focal seizures and alleviating neuronal damage [22], and therefore presents a potential novel human anti-seizure drug candidate which possesses broad efficacy against a range of seizure types.…”

Section: Discussionmentioning

confidence: 99%

“…The strain is commonly used to study the pathophysiology of epilepsy development [20], as well as to assess new anti-seizure treatments [21], with the pharmaco-responsivity resembling human absence seizures. Here we assessed whether NRP2945, previously shown to be able to fully prevent convulsive cortical seizures in the acute rat PTZ model [22], has efficacy against absence seizures in GAERS. We were motivated to study this model since NRP2945, and Neural Regeneration Peptides in…”

Section: Gaers (Genetic Absence Epilepsy Rats From Strasbourg) Are a mentioning

confidence: 99%

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Disease-Modifying Effects of Neural Regeneration Peptide 2945 in the GAERS Model of Absence Epilepsy

et al. 2017

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Epilepsy is a common neurological condition characterised by spontaneous recurrent seizures. Current anti-epileptic drugs are only effective and tolerated in ~70% of patients, leaving a substantial proportion of patients untreated. As such, there is a pressing need to develop new therapies. We assessed the anti-seizure activity of Neural Regeneration Peptide 2945 (NRP 2945) in the GAERS model of absence epilepsy. Drug effects on seizures were assessed using two study designs. Male adult GAERS were implanted with EEG electrodes to measure seizure frequency. The first study compared the effects of acute sc injection of vehicle, NRP 10 µg/kg, NRP 20 µg/kg, and controlled against the active comparator Valproaic acid (200 mg/kg). In the second study, animals received one of four treatments for 4 weeks: vehicle, NRP 60 µg/kg/day, NRP 120 µg/kg/day (delivered by continuous infusion) or NRP 20 µg/kg sc injected every second day (e.s.d). In the acute study, we found significant (p < 0.01) anti-seizure effects in animals treated with NRP2945 (20 µg/kg) and VPA, with NRP2945 slightly more efficacious, despite the 70,000 times lower molar dosage. In the chronic study, animals receiving 120 µg/kg/day and NRP 20 µg/kg e.s.d had significantly fewer seizures (p < 0.001), compared with vehicle. These effects were sustained for at least 10 days after drug treatment had ceased, indicative of disease-modifying activity. We demonstrate sustained anti-seizure effects of NRP2945, a potent small molecule peptide which enters the brain and is devoid of adverse effects. Early stage first-in-man trials have been initiated for subcutaneously delivered NRP2945 which is a promising step to providing therapeutic benefits for refractory epilepsy patients.

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“…To perform immunohistochemistry, following embedding in para n, the brain samples were processed after maintaining in 4% PFA for four days at 4°C. The samples were cut into 8-μm thick coronal sections [15].…”

Section: Sacri Ce and Brain Dissectionmentioning

confidence: 99%

Origanum vulgare prevents kaolin–induced hydrocephalus via regulation of GFAP and lba1 proteins expression in the rat brain

Vahabzadeh

Moazam

Rahimi

et al. 2022

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Background:The reactive gliosis contributes to patterns of hydrocephalus injury and recovery. The study aimed at evaluating Origanum vulgare essential oil (OEO) effects on reactive astrogliosis and reduced lateral ventricle thickness in kaolin-induced hydrocephalic rats. Methods and Results:Thirty male Wistar rats received kaolin via a direct injection into the cisterna magna and compared to control animals. After 21 day post-injection of kaolin, the hydrocephalic rats were randomly divided to four groups and experimental groups underwent magnetic resonance imaging to determine the lateral ventricle volume. Rats received different doses of OEO for 10 days. The lateral ventricular dilatation was evaluated by MRI. Also to assess the Iba-1 and GFAP proteins’ expression level, immunohistochemistry test and western blot analysis were performed 10 days after the injection. The results showed lateral ventricular size in the OEO-treated hydrocephalic rats was smaller than that of those receiving kaolin without OEO. The hydrocephalic rats increased reactive astrocytes and reactive microglia compared to the OEO-treated animals based on GFAP and Iba-1 immunoreactivity results. The findings were confirmed by western blot. There were significant differences between the hydrocephalus control and the 200 mg/kg/day OEO-treated rats in terms of GFAP and Iba-1 expression levels. Conclusions:In nonclusions, the OEO treated groups had stabilized ventricular expansion compared to hydrocephalus rats. Findings of the study showed that OEO can restrain the hydrocephalus-associated damage in rat brain induced by kaolin, likely by reducing GFAP and Iba-1 and therefore the OEO intervention, might be useful as a new treatment strategy.

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Anticonvulsant effect of neural regeneration peptide 2945 on pentylenetetrazol-induced seizures in rats

Cited by 16 publications

References 50 publications

CD8+ T Cell-Mediated Neuronal Dysfunction and Degeneration in Limbic Encephalitis

CD8+ T Cell-Mediated Neuronal Dysfunction and Degeneration in Limbic Encephalitis

Disease-Modifying Effects of Neural Regeneration Peptide 2945 in the GAERS Model of Absence Epilepsy

Origanum vulgare prevents kaolin–induced hydrocephalus via regulation of GFAP and lba1 proteins expression in the rat brain

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