Prolonged seizure suppression by a single implantable polymeric-TRH microdisk preparation

Area of Science:

• Neuroscience
• Pharmacology
• Biomaterials Science

Background:

• Thyrotropin-releasing hormone (TRH) exhibits anticonvulsant properties.
• Neuropeptide delivery faces challenges due to limited bioavailability.
• Developing sustained-release systems is crucial for effective neuropeptide therapy.

Purpose of the Study:

• To develop a sustained-release formulation of TRH using a biodegradable polyanhydride copolymer.
• To evaluate the anticonvulsant efficacy of the TRH-loaded microdisk in the rat kindling model of epilepsy.
• To assess the long-term effects of TRH delivery on seizure suppression.

Main Methods:

• TRH was incorporated into a biodegradable polyanhydride copolymer microdisk.
• Microdisks were stereotaxically implanted into the amygdala, a seizure focus, in rats.
• Kindling development and seizure severity indices (afterdischarge duration, clonus duration) were measured.
• The effects of a single TRH microdisk implantation were compared to control groups.

Main Results:

• A single TRH microdisk implantation significantly suppressed kindling progression.
• Seizure severity, including afterdischarge and clonus duration, was markedly reduced.
• Significant anticonvulsant effects, particularly on clonus duration, persisted for at least 50 days post-implantation.
• The number of stimulations required to reach full kindling was significantly higher in the TRH-treated group.

Conclusions:

• In situ microdisk pharmacotherapy with TRH provides sustained-release delivery and effective seizure suppression.
• This approach demonstrates potential for treating intractable epilepsy.
• The findings support the use of biodegradable polymer-based drug delivery for neuropeptide therapy in neurological disorders.