A longitudinal MRI and TSPO PET-based investigation of brain region-specific neuroprotection by diazepam versus midazolam following organophosphate-induced seizures
Neuropharmacology. 2024 Mar 23:109918. doi: 10.1016/j.neuropharm.2024.109918. Online ahead of print.ABSTRACTAcute poisoning with organophosphorus cholinesterase inhibitors (OPs), such as OP nerve agents and pesticides, can cause life threatening cholinergic crisis and status epilepticus (SE). Survivors often experience significant morbidity, including brain injury, acquired epilepsy, and cognitive deficits. Current medical countermeasures for acute OP poisoning include a benzodiazepine to mitigate seizures. Diazepam was long the benzodiazepine included in autoinjectors used to treat OP-induced seizures, but it is now being...
Source: Neuropharmacology - March 25, 2024 Category: Drugs & Pharmacology Authors: Brad A Hobson Douglas R Rowland Yimeng Dou Naomi Saito Zachary T Harmany Donald A Bruun Danielle J Harvey Abhijit Chaudhari Joel R Garbow Pamela J Lein Source Type: research

A longitudinal MRI and TSPO PET-based investigation of brain region-specific neuroprotection by diazepam versus midazolam following organophosphate-induced seizures
Neuropharmacology. 2024 Mar 23:109918. doi: 10.1016/j.neuropharm.2024.109918. Online ahead of print.ABSTRACTAcute poisoning with organophosphorus cholinesterase inhibitors (OPs), such as OP nerve agents and pesticides, can cause life threatening cholinergic crisis and status epilepticus (SE). Survivors often experience significant morbidity, including brain injury, acquired epilepsy, and cognitive deficits. Current medical countermeasures for acute OP poisoning include a benzodiazepine to mitigate seizures. Diazepam was long the benzodiazepine included in autoinjectors used to treat OP-induced seizures, but it is now being...
Source: Neuropharmacology - March 25, 2024 Category: Drugs & Pharmacology Authors: Brad A Hobson Douglas R Rowland Yimeng Dou Naomi Saito Zachary T Harmany Donald A Bruun Danielle J Harvey Abhijit Chaudhari Joel R Garbow Pamela J Lein Source Type: research

A longitudinal MRI and TSPO PET-based investigation of brain region-specific neuroprotection by diazepam versus midazolam following organophosphate-induced seizures
Neuropharmacology. 2024 Mar 23:109918. doi: 10.1016/j.neuropharm.2024.109918. Online ahead of print.ABSTRACTAcute poisoning with organophosphorus cholinesterase inhibitors (OPs), such as OP nerve agents and pesticides, can cause life threatening cholinergic crisis and status epilepticus (SE). Survivors often experience significant morbidity, including brain injury, acquired epilepsy, and cognitive deficits. Current medical countermeasures for acute OP poisoning include a benzodiazepine to mitigate seizures. Diazepam was long the benzodiazepine included in autoinjectors used to treat OP-induced seizures, but it is now being...
Source: Neuropharmacology - March 25, 2024 Category: Drugs & Pharmacology Authors: Brad A Hobson Douglas R Rowland Yimeng Dou Naomi Saito Zachary T Harmany Donald A Bruun Danielle J Harvey Abhijit Chaudhari Joel R Garbow Pamela J Lein Source Type: research

Small-molecule caspase-1 inhibitor CZL80 terminates refractory status epilepticus via inhibition of glutamatergic transmission
In this study, we highlight the therapeutic potential of CZL80, a small molecule that inhibits caspase-1, in SE termination and its related mechanisms. We found that delayed treatment of diazepam (0.5 h) easily induces resistance in kainic acid (KA)-induced SE. CZL80 dose-dependently terminated diazepam-resistant SE, extending the therapeutic time window to 3 h following SE, and also protected against neuronal damage. Interestingly, the effect of CZL80 on SE termination was model-dependent, as evidenced by ineffectiveness in the pilocarpine-induced SE. Further, we found that CZL80 did not terminate KA-induced SE in Caspase...
Source: Acta Pharmacologica Sinica - March 22, 2024 Category: Drugs & Pharmacology Authors: Fei Wang Yu Wang Qing-Yang Zhang Ke-Yu Hu Ying-Jie Song Lin Yang Fan Fei Ceng-Lin Xu Sun-Liang Cui Ye-Ping Ruan Yi Wang Zhong Chen Source Type: research

Small-molecule caspase-1 inhibitor CZL80 terminates refractory status epilepticus via inhibition of glutamatergic transmission
In this study, we highlight the therapeutic potential of CZL80, a small molecule that inhibits caspase-1, in SE termination and its related mechanisms. We found that delayed treatment of diazepam (0.5 h) easily induces resistance in kainic acid (KA)-induced SE. CZL80 dose-dependently terminated diazepam-resistant SE, extending the therapeutic time window to 3 h following SE, and also protected against neuronal damage. Interestingly, the effect of CZL80 on SE termination was model-dependent, as evidenced by ineffectiveness in the pilocarpine-induced SE. Further, we found that CZL80 did not terminate KA-induced SE in Caspase...
Source: Acta Pharmacologica Sinica - March 22, 2024 Category: Drugs & Pharmacology Authors: Fei Wang Yu Wang Qing-Yang Zhang Ke-Yu Hu Ying-Jie Song Lin Yang Fan Fei Ceng-Lin Xu Sun-Liang Cui Ye-Ping Ruan Yi Wang Zhong Chen Source Type: research

Prevalence of use of on-label and off-label psychotropics in the Greek pediatric population
With a global increased use of psychotropics in pediatrics, their off-label use is a concern due to uncertainty and risk. Data on psychotropics use in the Greek pediatric population do not exist to date. We analyzed retrospective data from the nationwide pharmacy claim database, to estimate the prevalence of psychotropics in pediatrics focusing on off-label use (March 2016-October 2019). In total 63,782 pediatric subjects had at least one identified psychotropic prescription. The prevalence of psychotropics use was 5.1–14.6/1,000 pediatric inhabitants. When excluding 42,508 subjects who received only short-time hydroxyzi...
Source: Frontiers in Pharmacology - March 14, 2024 Category: Drugs & Pharmacology Source Type: research

Characterization of the intrahippocampal kainic acid model in female mice with a special focus on seizure suppression by antiseizure medications
Exp Neurol. 2024 Mar 9:114749. doi: 10.1016/j.expneurol.2024.114749. Online ahead of print.ABSTRACTDespite special challenges in the medical treatment of women with epilepsy, in particular preclinical animal studies were focused on males for decades and females have only recently moved into the focus of scientific interest. The intrahippocampal kainic acid (IHKA) mouse model of temporal lobe epilepsy (TLE) is one of the most studied models in males reproducing electroencephalographic (EEG) and histopathological features of human TLE. Hippocampal paroxysmal discharges (HPDs) were described as drug resistant focal seizures i...
Source: Experimental Neurology - March 11, 2024 Category: Neurology Authors: Melanie Widmann Andreas Lieb Barbara Fogli Angela Steck Anna Mutti Christoph Schwarzer Source Type: research

Characterization of the intrahippocampal kainic acid model in female mice with a special focus on seizure suppression by antiseizure medications
Exp Neurol. 2024 Mar 9:114749. doi: 10.1016/j.expneurol.2024.114749. Online ahead of print.ABSTRACTDespite special challenges in the medical treatment of women with epilepsy, in particular preclinical animal studies were focused on males for decades and females have only recently moved into the focus of scientific interest. The intrahippocampal kainic acid (IHKA) mouse model of temporal lobe epilepsy (TLE) is one of the most studied models in males reproducing electroencephalographic (EEG) and histopathological features of human TLE. Hippocampal paroxysmal discharges (HPDs) were described as drug resistant focal seizures i...
Source: Experimental Neurology - March 11, 2024 Category: Neurology Authors: Melanie Widmann Andreas Lieb Barbara Fogli Angela Steck Anna Mutti Christoph Schwarzer Source Type: research

Characterization of the intrahippocampal kainic acid model in female mice with a special focus on seizure suppression by antiseizure medications
Exp Neurol. 2024 Mar 11;376:114749. doi: 10.1016/j.expneurol.2024.114749. Online ahead of print.ABSTRACTDespite special challenges in the medical treatment of women with epilepsy, in particular preclinical animal studies were focused on males for decades and females have only recently moved into the focus of scientific interest. The intrahippocampal kainic acid (IHKA) mouse model of temporal lobe epilepsy (TLE) is one of the most studied models in males reproducing electroencephalographic (EEG) and histopathological features of human TLE. Hippocampal paroxysmal discharges (HPDs) were described as drug resistant focal seizu...
Source: Experimental Neurology - March 11, 2024 Category: Neurology Authors: Melanie Widmann Andreas Lieb Barbara Fogli Angela Steck Anna Mutti Christoph Schwarzer Source Type: research

Evaluation of prognostic scores for status epilepticus in the neurology ICU: A retrospective study
Status epilepticus (SE) in the neurology intensive care unit (ICU) is associated with significant morbidity. We aimed to evaluate the utility of existing prognostic scores, namely the Status Epilepticus Severity Score (STESS), Epidemiology Based Mortality Score in Status Epilepticus (EMSE)-EACE and Encephalitis-Nonconvulsive Status Epilepticus-Diazepam Resistance-Image Abnormalities-Tracheal Intubation (END-IT), among SE patients in the neurology ICU. (Source: Journal of the Neurological Sciences)
Source: Journal of the Neurological Sciences - March 10, 2024 Category: Neurology Authors: Jia Yi Shen, Seyed Ehsan Saffari, Linda Yong, Nigel Choon Kiat Tan, Yee-Leng Tan Source Type: research

A-series agent A-234: initial in vitro and in vivo characterization
This study is the first to provide essential experimental preclinical data on the A-234 compound.PMID:38446233 | DOI:10.1007/s00204-024-03689-3 (Source: Archives of Toxicology)
Source: Archives of Toxicology - March 6, 2024 Category: Toxicology Authors: Martina Hrabinova Jaroslav Pejchal Vendula Hepnarova Lubica Muckova Lucie Junova Jakub Opravil Jana Zdarova Karasova Tomas Rozsypal Alzbeta Dlabkova Helena Rehulkova Tomas Kucera Zbyn ěk Vecera Filip Caisberger Monika Schmidt Ondrej Soukup Daniel Jun Source Type: research

A-series agent A-234: initial in vitro and in vivo characterization
This study is the first to provide essential experimental preclinical data on the A-234 compound.PMID:38446233 | DOI:10.1007/s00204-024-03689-3 (Source: Archives of Toxicology)
Source: Archives of Toxicology - March 6, 2024 Category: Toxicology Authors: Martina Hrabinova Jaroslav Pejchal Vendula Hepnarova Lubica Muckova Lucie Junova Jakub Opravil Jana Zdarova Karasova Tomas Rozsypal Alzbeta Dlabkova Helena Rehulkova Tomas Kucera Zbyn ěk Vecera Filip Caisberger Monika Schmidt Ondrej Soukup Daniel Jun Source Type: research

A-series agent A-234: initial in vitro and in vivo characterization
This study is the first to provide essential experimental preclinical data on the A-234 compound.PMID:38446233 | DOI:10.1007/s00204-024-03689-3 (Source: Archives of Toxicology)
Source: Archives of Toxicology - March 6, 2024 Category: Toxicology Authors: Martina Hrabinova Jaroslav Pejchal Vendula Hepnarova Lubica Muckova Lucie Junova Jakub Opravil Jana Zdarova Karasova Tomas Rozsypal Alzbeta Dlabkova Helena Rehulkova Tomas Kucera Zbyn ěk Vecera Filip Caisberger Monika Schmidt Ondrej Soukup Daniel Jun Source Type: research

A-series agent A-234: initial in vitro and in vivo characterization
This study is the first to provide essential experimental preclinical data on the A-234 compound.PMID:38446233 | DOI:10.1007/s00204-024-03689-3 (Source: Archives of Toxicology)
Source: Archives of Toxicology - March 6, 2024 Category: Toxicology Authors: Martina Hrabinova Jaroslav Pejchal Vendula Hepnarova Lubica Muckova Lucie Junova Jakub Opravil Jana Zdarova Karasova Tomas Rozsypal Alzbeta Dlabkova Helena Rehulkova Tomas Kucera Zbyn ěk Vecera Filip Caisberger Monika Schmidt Ondrej Soukup Daniel Jun Source Type: research

The effects of diazepam on fear extinction in nulliparous and primiparous female rats
Horm Behav. 2024 Feb 28;161:105518. doi: 10.1016/j.yhbeh.2024.105518. Online ahead of print.ABSTRACTBenzodiazepines undermine the success of exposure therapy in humans with anxiety disorders, and impair the long-term memory of fear extinction (the laboratory basis of exposure therapy) in rodents. However, most rodent studies on fear extinction and benzodiazepines have been conducted in male rodents. In female rodents, the estrous cycle influences the consolidation of fear extinction memories and sensitivity to benzodiazepines. In addition, pregnancy leads to long-term changes in the neurobiological, hormonal, and behaviour...
Source: Hormones and Behavior - February 29, 2024 Category: Endocrinology Authors: Jodie E Pestana Tasfia Kabir Bronwyn M Graham Source Type: research