Long-term behavioral, electrophysiological, and neurochemical monitoring of the safety of an experimental antiepileptic implant, the muscimol-delivering Subdural Pharmacotherapy Device in monkeys.

Object: The authors evaluated the extent to which the Subdural Pharmacotherapy Device (SPD), chronically implanted over the frontal cortex to perform periodic, localized muscimol-delivery/CSF removal cycles, affects overall behavior, motor performance, electroencephalography (EEG) activity, and blood and CSF neurochemistry in macaque monkeys.

Methods: Two monkeys were used to adjust methodology and 4 monkeys were subjected to comprehensive testing. Prior to surgery, the animals' behavior in a large test chamber was monitored, and the motor skills required to remove food pellets from food ports located on the walls of the chamber were determined.

An implantable triple-function device for local drug delivery, cerebrospinal fluid removal and EEG recording in the cranial subdural/subarachnoid space of primates.

Transmeningeal pharmacotherapy for cerebral cortical disorders requires drug delivery through the subdural/subarachnoid space, ideally with a feedback controlled mechanism. We have developed a device suitable for this function. The first novel component of the apparatus is a silicone rubber strip equipped with (a) fluid-exchange ports for both drug delivery and local cerebrospinal fluid (CSF) removal, and (b) EEG recording electrode contacts.

Transmeningeal muscimol can prevent focal EEG seizures in the rat neocortex without stopping multineuronal activity in the treated area.

Muscimol has potent antiepileptic efficacy after transmeningeal administration in animals. However, it is unknown whether this compound stops local neuronal firing at concentrations that prevent seizures. The purpose of this study was to test the hypothesis that epidurally administered muscimol can prevent acetylcholine (Ach)-induced focal seizures in the rat neocortex without causing cessation of multineuronal activity.

A high-performance transcutaneous battery charger for medical implants.

As new functionality is added to the implantable devices, their power requirements also increase. Such power requirements make it hard for keeping such implants operational for long periods by non-rechargeable batteries. This result in a need for frequent surgeries to replace these batteries.

Evolution and prospects for intracranial pharmacotherapy for refractory epilepsies: the subdural hybrid neuroprosthesis.

Intracranial pharmacotherapy is a novel strategy to treat drug refractory, localization-related epilepsies not amenable to resective surgery. The common feature of the method is the use of some type of antiepileptic drug (AED) delivery device placed inside the cranium to prevent or stop focal seizures. This distinguishes it from other nonconventional methods, such as intrathecal pharmacotherapy, electrical neurostimulation, gene therapy, cell transplantation, and local cooling.

Localized transmeningeal muscimol prevents neocortical seizures in rats and nonhuman primates: therapeutic implications.

Purpose: To determine whether muscimol delivered epidurally or into the subarachnoid space can prevent and/or terminate acetylcholine (Ach)-induced focal neocortical seizures at concentrations not affecting behavior and background electroencephalography (EEG) activity.

Methods: Rats (n = 12) and squirrel monkeys (n = 3) were chronically implanted with an epidural or subarachnoid drug delivery device, respectively, over the right frontal/parietal cortex, with adjacent EEG electrodes. Recordings were performed in behaving rats and chaired monkeys.

The use of a remote-controlled minivalve, carried by freely moving animals on their head, to achieve instant pharmacological effects in intracerebral drug-perfusion studies.

Intracerebral drug-perfusion studies in animals can be very efficiently performed with the 'reverse-dialysis' procedure. In this procedure, drugs are delivered into the brain via an intracerebrally implanted microdialysis probe. Traditionally, in reverse-dialysis studies the flow of control and drug solutions in the microdialysis site is alternated by large and heavy valves placed far from the experimental animal.