Deep Brain Stimulation Results in Local Glutamate and Adenosine Release

Tawfik, Vivianne L.; Su, Chang; Hitti, Frederick L.; Roberts, David W.; Leiter, James C.; Jovanović, Svetlana; Lee, Kendall H.

doi:10.1227/01.neu.0000371988.73620.4c

Cited by 129 publications

(118 citation statements)

References 60 publications

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“…Cunha et al [39] reported that levels of adenosine in hippocampal slices were increased by high-frequency, but not low-frequency stimulation, and recently, the involvement of adenosine in the therapeutic mechanism of thalamic DBS has been suggested [40,41] . The marked suppression and slow recovery of both spontaneous and ictal activity following high-frequency DBS bursts are consistent with this type of metabotropic regulatory mechanism; however, direct evidence is not provided by our results.…”

Section: Discussionmentioning

confidence: 99%

Development of a Large Animal Model for Investigation of Deep Brain Stimulation for Epilepsy

Stypulkowski

Giftakis

Billstrom

2011

Stereotact Funct Neurosurg

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Background/Objectives: To better understand the mechanism of action of deep brain stimulation (DBS) for epilepsy and to investigate implantable device features, it is desirable to have a large animal model to evaluate clinical-grade systems. This study assessed the suitability of an ovine model of epilepsy for this purpose. Methods: Animals were anesthetized for surgery and 1.5 T MRIs collected. Unilateral anterior thalamic DBS leads, hippocampal depth electrodes and catheters were implanted using a frameless stereotactic system. Evoked responses and local field potentials were collected and stored for off-line analysis. Results: Despite limited neuroanatomic information for this species, it was possible to reliably implant leads into the target structures using MR-guided techniques. Stimulation of these regions produced robust evoked potentials within this circuit that were dependent on stimulus location and parameters. High-frequency thalamic DBS produced a clear inhibition of both spontaneous and penicillin-induced ictal activity in the hippocampus which far outlasted the duration of the stimulation. Conclusions: These preliminary results suggest that the sheep model may be useful for further investigation of DBS for epilepsy. The demonstration of marked suppression of network excitability with high-frequency stimulation supports a potential therapeutic mechanism for this DBS therapy.

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Section: Discussionmentioning

confidence: 99%

Development of a Large Animal Model for Investigation of Deep Brain Stimulation for Epilepsy

Stypulkowski

Giftakis

Billstrom

2011

Stereotact Funct Neurosurg

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“…This is important in light of recent evidence suggesting that PFC glia might be involved in mechanisms of depressivelike behavior and antidepressant treatments in rats (65,66). Furthermore, adenosine and glutamate released by glial cells have been shown to contribute to the mechanisms of thalamic DBS in vitro (67). At present, there is still no conclusive evidence supporting a role for glia in the antidepressant-like effects of vmPFC DBS.…”

Section: Mechanisms Involved In the Effects Of Vmpfc Stimulation In Tmentioning

confidence: 94%

Preclinical Studies Modeling Deep Brain Stimulation for Depression

Hamani¹,

Nóbrega²

2012

Biological Psychiatry

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Deep brain stimulation (DBS) is currently being investigated for the treatment of depression. Results of early clinical trials have been very promising, but the mechanisms responsible for the effects of DBS are still unknown. This article reviews behavioral findings of stimulation applied to different brain targets in rodents, with a particular focus on the ventromedial prefrontal cortex. Mechanisms and substrates involved in the antidepressant-like effects of DBS, including the role of local tissue inactivation, the modulation of fiber pathways in the vicinity of the electrodes, as well as the importance of the serotonergic system and brain derived neurotrophic factor are discussed. KeywordsAnimal models; deep brain stimulation; depression; fiber pathways; psychiatry; radiofrequency lesions; serotonin Deep brain stimulation (DBS) has been investigated for the treatment of depression with promising clinical results (1-11). Although preclinical research using electrical stimulation to study behavior has been conducted for over 50 years, results from animal studies did not comprise the rationale for the current use of DBS in depression. Experiments i n animal models to investigate substrates and mechanisms responsible for the antidepressant-like effects of DBS were only conducted after the initial clinical trials were published (2,7,8,(10)(11)(12).This article provides an overview of current findings and some of the emerging concepts from experiments with DBS in models of depression, with a particular focus on results obtained with ventromedial prefrontal cortex (vmPFC) stimulation in rodents. CIHR Author Manuscript CIHR Author Manuscript CIHR Author Manuscript Choosing a Stimulation TargetThe medial surface of the frontal cortex in rodents has been subdivided into four cytoarchitectural regions: the agranular frontal cortex, anterior cingulate cortex (AC), prelimbic cortex (PL), and infralimbic cortex(IL)( Figure 1A)(13-15).Alternatively, it has also been subdivided into dorsal and ventral "systems," according to functional role as well as afferent and efferent projections (15). The dorsal system includes the frontal agranular cortex, AC, and dorsal PL and seems to be involved in the control of eye and head movements (14-16). The ventral system, comprises the IL and ventral aspects of the PL (vPL), projects mainly to the amygdala, hypothalamus, insula, and brainstem and has been suggested to play a role in autonomic control (17)(18)(19)(20). Vertes (21) proposed an alternative subdivision of the medial prefrontal cortex (PFC) in dorsal (frontal agranular cortex and AC) and ventral regions (PL and IL). To mimic the effects of subgenual cingulum (SCG) DBS in rodents, we have been applying stimulation to the vmPFC (12,(22)(23)(24)(25)(26), including IL and vPL.Overall, the limits of the vPL are hard to delineate. However, if an arbitrary line is traced dividing the PL into dorsal and ventral halves, the approximate anteroposterior, mediolateral, and dorsoventral dimensions of the vmPFC (including IL and vPL...

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“…The electrical current also acts on synapses and triggers adjacent astrocytes to release a wave of calcium and to promote local release of neurotransmitters (e.g. adenosine and glutamate) from excitatory efferent neurons [8,9,10]. In addition, this intervention produces global increases in cerebral blood flow [11] and stimulates neurogenesis [12].…”

Section: Mechanisms Of Dbsmentioning

confidence: 99%