Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thyrotropin-releasing hormone (TRH; Protirelin), an endogenous neuropeptide, is known to have anticonvulsant effects in animal seizure models and certain intractable epileptic patients. Its duration of action, however, is limited by rapid tissue metabolism and the blood-brain barrier. Direct nose-to-brain delivery of neuropeptides in sustained-release biodegradable nanoparticles (NPs) is a promising mode of therapy for enhancing CNS neuropeptide bioavailability. To provide proof of principle for this delivery approach, we used the kindling model of temporal lobe epilepsy to show that 1) TRH-loaded copolymer microdisks implanted in a seizure focus can attenuate kindling development in terms of behavioral stage, afterdischarge duration (ADD), and clonus duration; 2) intranasal administration of an unprotected TRH analog can acutely suppress fully kindled seizures in a concentration-dependent manner in terms of ADD and seizure stage; and 3) intranasal administration of polylactide nanoparticles (PLA-NPs) containing TRH (TRH-NPs) can impede kindling development in terms of behavioral stage, ADD, and clonus duration. Additionally, we used intranasal delivery of fluorescent dye-loaded PLA-NPs in rats and application of dye-loaded or dye-attached NPs to cortical neurons in culture to demonstrate NP uptake and distribution over time in vivo and in vitro respectively. Also, a nanoparticle immunostaining method was developed as a procedure for directly visualizing the tissue level and distribution of neuropeptide-loaded nanoparticles. Collectively, the data provide proof of concept for intranasal delivery of TRH-NPs as a viable means to 1) suppress seizures and perhaps epileptogenesis and 2) become the lead compound for intranasal anticonvulsant nanoparticle therapeutics.
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PMID:Attenuation of kindled seizures by intranasal delivery of neuropeptide-loaded nanoparticles. 1933 33

We here report on a male infant with Ohtahara syndrome. Tonic spasms in series appeared in an one-month-old baby, with his EEG showing a typical suppression burst pattern. We attempted these therapies in the following order; high-dose pyridoxal phosphate; anti-epileptic drugs; sodium valproate, phenobarbital, clonazepam and clobazam in various doses and combination; ACTH; TRH; and gamma-globulin. These did not, however, prove effective enough. Then we tried the ketogenic diet and brought his seizures under control. Therefore, we recommend that doctors who treat Ohtahara syndrome consider using the ketogenic diet earlier in the treatment regimen if the patient does not seem to be responding to conventional drug therapies.
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PMID:[The ketogenic diet as an effective treatment for Ohtahara syndrome]. 2140 Sep 32


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