Tissue reactions to long-term electrical stimulation of the cerebellum in monkeys

Abstract

Light and electron microscopic analyses were carried out on the stimulated and unstimulated paravermal cortices of six rhesus monkeys that had electrodes implanted on their cerebella for 2 months. The electrodes and the stimulation regime (10 p.p.s.: 8 min on, 8 min off) were similar to those used to stimulate the human cerebellum for treatment of certain neurological disorders. Mere presence of the electrode array in the posterior fossa for 2 months resulted in some meningeal thickening, attenuation of the molecular layer, and loss of Purkinje cells immediately beneath the electrode array. There was no evidence of scarring. After 205 hours of stimulation (7.35 X 10(6) pulses) over 18 days, a charge of 0.5 muC/ph or estimated charge density of 7.4 muC/sq cm/ph resulted in no damage to the cerebellum attributable to electrical stimulation per se. Such a charge/phase is about five times the threshold for evocation of cerebellar efferent activity, and might be considered "safe" for stimulation of human cerebellum. Charge density/phase and charge/phase were directly related to increased cerebellar injury in the six other cerebellar cortices stimulated. Leptomeningeal thickening increased with increased charge density. Injury included severe molecular layer attenuation, ongoing destruction of Purkinje cells, gliosis, ongoing degeneration of myelinated axons, collagen intrusion, and increased levels of local polysaccharides. In all cases, even with damage that destroyed all conducting elements beneath the electrodes, there was no damage further than 1 to 2 mm from the edges of the electrode arrays.

Cerebellar stimulation in the management of medically intractable epilepsy: a systematic and critical review

“…Numerous animal studies have demonstrated that electrical stimulation of the cerebellum may abort electrically or chemically induced seizures and drastically alter the electrophysiological profile of the neuronal tissue in vitro and in vivo. 1,2,5,8,[13][14][15]19,21,22,26,28,30,35,38,39,41,42,48,49,52,53 However, there are several issues that remain to be resolved and important questions that need to be answered.…”

“…The vast majority of the animal experimental studies but also the clinical trials have used the cerebellum cortical surface as stimulation target, with frequently contradictory results. 8,5,[14][15][16]22,23,38,48,52,53 However, the stimulation of the deep cerebellar nuclei appears to provide more solid data and better seizure control. 1,35 There are several mechanisms that may explain this discrepancy in the results of the cortical CS in animal and human studies.…”

“…Godlevskii et al, 19 using a penicillin-induced seizure model, found that cortical stimulation of the paleocerebellum resulted in a decreased amount of interictal spikes, but had no effect on actual seizure activity. In addition, Brown et al, 5,13 working on a monkey seizure model in which electrical cortical stimulation was used to abort seizures, performed light and electron microscopic examinations of cerebellum specimens obtained in the experimental animals. Specimen examination revealed attenuation of the molecular layer of the cerebellum cortex and loss of Purkinje cells in the surface areas of electrode contact.…”

Electrochemically controlled release of dexamethasone from conducting polymer polypyrrole coated electrode

“…The chronic application of these devices has been limited by their unpredictable failure over extended periods. Although the precise mechanism for this failure is not completely known, it is suggested that an undesirable brain tissue reaction to the device leads to the formation of a glial scar which then serves as a barrier to neural signal transduction [1][2][3][4][5][6][7][8].…”

Deep brain stimulation for medically refractory epilepsy

“…Mutani and colleagues 60 demonstrated that CS temporarily reduced cobalt-induced spiking in the cerebral cortex of cats. Eight years later, Brown et al 10 reported on tissue reactions after 2 months of electrical stimulation in the cerebellum of monkeys undergoing CS. Light and electron microscopic analyses revealed that the mere presence of the electrode array on the surface led to attenuation of the molecular layer and loss of Purkinje cells in adjacent tissue.…”