Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 3 of 3
Full-Text Articles in Medicine and Health Sciences
Proconvulsant Actions Of Intrahippocampal Botulinum Neurotoxin B In The Rat, Sonja Bröer, Dorota Zolkowska, Manuela Gernert, Michael A. Rogawski
Proconvulsant Actions Of Intrahippocampal Botulinum Neurotoxin B In The Rat, Sonja Bröer, Dorota Zolkowska, Manuela Gernert, Michael A. Rogawski
Michael A. Rogawski
Botulinum neurotoxins (BoNTs) may affect the excitability of brain circuits by inhibiting neurotransmitter release at central synapses. There is evidence that local delivery of BoNT serotypes A and E, which target synaptosomal-associated protein 25, a component of the release machinery specific to excitatory synapses, can inhibit seizure generation. BoNT serotype B (BoNT/B) targets VAMP2, which is expressed in both excitatory and inhibitory terminals. Here we assessed the effects of unilateral intrahippocampal infusion of BoNT/B in the rat on intravenous pentylenetetrazol (PTZ) seizure thresholds, and on the expression of spontaneous behavioral and electrographic seizures. Infusion of BoNT/B (500 and 1000 Unit) …
Seizure Protection By Intrapulmonary Delivery Of Midazolam In Mice, Ashish Dhir, Dorota Zolkowska, Michael A. Rogawski
Seizure Protection By Intrapulmonary Delivery Of Midazolam In Mice, Ashish Dhir, Dorota Zolkowska, Michael A. Rogawski
Michael A. Rogawski
The lung provides a portal of entry that could be used to rapidly deliver anticonvulsant substances to the brain to treat seizures. In the present study, we demonstrate that midazolam, a water-soluble anticonvulsant benzodiazepine, confers potent seizure protection when administered via the intrapulmonary route. High dose (100 mg/kg) intraperitoneal midazolam induced loss-of-righting reflex in mice. Lower doses of midazolam (100–1000 μg/kg) when administered intraperitoneally did not induce loss-of-righting reflex but protected animals against pentylenetetrazol (PTZ)-induced seizures. Intrapulmonary administration of midazolam via a tracheal cannula protected against intraperitoneal PTZ seizures at lower doses. The minimal intraperitoneal and intravenous doses of midazolam …
Neuroactive Steroids For The Treatment Of Status Epilepticus, Michael Rogawski, Carlos Loya, Kiran Reddy, Dorota Zolkowski, Christoph Lossin
Neuroactive Steroids For The Treatment Of Status Epilepticus, Michael Rogawski, Carlos Loya, Kiran Reddy, Dorota Zolkowski, Christoph Lossin
Michael A. Rogawski
Benzodiazepines are the current first-line standard-of-care treatment for status epilepticus but fail to terminate seizures in about one third of cases. Synaptic GABA-A receptors, which mediate phasic inhibition in central circuits, are the molecular target of benzodiazepines. As status epilepticus progresses, these receptors are internalized and become functionally inactivated, conferring benzodiazepine resistance, which is believed to be a major cause of treatment failure. GABA-A receptor positive allosteric modulator neuroactive steroids, such as allopregnanolone, also potentiate synaptic GABA-A receptors, but in addition they enhance extrasynaptic GABA-A receptors that mediate tonic inhibition. Extrasynaptic GABA-A receptors are not internalized, and desensitization of these …