Publications by authors named "J Spampanato"
Article Synopsis
- Researchers are creating human telencephalic organoids from stem cells to better understand developmental processes related to uniquely human behaviors and disorders.
- These organoids show complex organization with various types of neural cells, allowing for detailed study of excitatory and inhibitory neuron development.
- The study also reveals specific deficits in organoids with a deletion of the SHANK3 gene, which is linked to autism and intellectual disabilities, highlighting the usefulness of these organoids for investigating neurological issues.
Benzodiazepines are the primary treatment option for organophosphate (OP)-induced status epilepticus (SE), but these antiseizure drugs (ASDs) lose efficacy as treatment is delayed. In the event of a mass civilian or military exposure, significant treatment delays are likely. New ASDs that combat benzodiazepine-resistant, OP-induced SE are critically needed, particularly if they can be efficacious after a long treatment delay.
View Article and Find Full Text PDFOrganophosphate (OP) exposure induces status epilepticus (SE), a medical emergency with high morbidity and mortality. Current standard medical countermeasures lose efficacy with time so that treatment delays, in the range of tens of minutes, result in increasingly poor outcomes. As part of the Countermeasures Against Chemical Threats Neurotherapeutics Screening Program, we previously developed a realistic model of delayed treatment of OP-induced SE using the OP diisopropyl fluorophosphate (DFP) to screen compounds for efficacy in the termination of SE and elimination of neuronal death.
View Article and Find Full Text PDFOrganophosphorus (OP) compounds are deadly chemicals that exert their intoxicating effects through the irreversible inhibition of acetylcholinesterase (AChE). In addition to an excess of peripheral ailments, OP intoxication induces status epilepticus (SE) which if left untreated may lead to permanent brain damage or death. Benzodiazepines are typically the primary therapies for OP-induced SE, but these drugs lose efficacy as treatment time is delayed.
View Article and Find Full Text PDFArticle Synopsis
- Seizures from organophosphorus nerve agents resist benzodiazepine treatment due to rapid internalization of synaptic GABA receptors, while extrasynaptic receptors remain available and are targeted for better management of these seizures.
- Neurosteroids, like allopregnanolone, show promise as alternatives because they activate both synaptic and extrasynaptic GABA receptors, offering longer-lasting effectiveness and protection against neuronal death, though their use is hampered by formulation challenges.
- A non-steroidal enaminone called 2-261 effectively terminated seizures for over 10 hours in animal models and reduced neuronal damage, though it acted slowly as a standalone treatment but enhanced the effectiveness of benzodiazepines.