Analysis of Gene Expression Changes in the Rat Hippocampus After Deep Brain Stimulation of the Anterior Thalamic Nucleus

Selvakumar, Tharakeswari; Alavian, Kambiz N.; Tierney, Travis S.

doi:10.3791/52457

Cited by 7 publications

(3 citation statements)

References 60 publications

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“…The reasons for this are unknown, but a few studies point to possible mechanisms. ANT DBS alters genes to increase brain‐derived neurotrophic factor (BDNF) and GABA receptor subunits, although these changes are transient 42 . Stimulation induces neurogenesis in hippocampus 43 and dentate gyrus 44 .…”

Section: Discussionmentioning

confidence: 99%

The SANTÉ study at 10 years of follow‐up: Effectiveness, safety, and sudden unexpected death in epilepsy

et al. 2021

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We evaluated the efficacy and safety of deep brain anterior thalamus stimulation after 7 and 10 years, and report the incidence of sudden unexpected death in epilepsy (SUDEP) and overall mortality in adults in the Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy (SANTÉ) study. Methods: After the 3-month blinded and 9-month unblinded phases, subjects continued to be assessed during long-term follow-up (LTFU) and later a continued therapy access phase (CAP), to further characterize adverse events and the incidence of SUDEP. Stimulus parameter and medication changes were allowed. Results: One hundred ten implanted subjects accumulated a total of 938 device-years of experience (69 subjects during the LTFU phase and 61 subjects in the CAP phase).Prior to study closure, 57 active subjects continued therapy at 14 study centers, with follow-up of at least 10 (maximum 14) years. At 7 years, median seizure frequency percent reduction from baseline was 75% (p < .001), with no outcome differences related to prior vagus nerve stimulation or resective surgery. The most severe seizure type, focal to bilateral tonic-clonic, was reduced by 71%. Adding new antiseizure medications did not impact the pattern of seizure reduction over time. There were no unanticipated serious adverse events in the study. The definite-plus-probable SUDEP rate, based on SANTÉ study experience (two deaths in 938 years) and previous pilot studies (0 deaths in 76 years), indicated a rate of 2.0 deaths for 1000 person-years.Overall mortality was 6.9 deaths per 1000 person-years. Significance: The long-term efficacy and safety profiles of the deep brain stimulation (DBS) system for epilepsy are favorable and demonstrate stable outcomes.Improvement in frequency of the most severe seizure type may reduce SUDEP risk.The SUDEP rate with DBS (2.0) is comparable to other neuromodulation treatments (i.e., vagus nerve stimulation, responsive neurostimulation) for drug-resistant focal epilepsy.

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Section: Discussionmentioning

confidence: 99%

The SANTÉ study at 10 years of follow‐up: Effectiveness, safety, and sudden unexpected death in epilepsy

et al. 2021

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“…So far, it is still unclear whether HFS influences the key molecular events that regulate cellular processes such as adult neurogenesis in vivo. Several lines of studies have demonstrated that HFS in rodents could mimic similar neural responses of clinically applied DBS 15,16 . To understand the underlying cellular mechanisms of HF-DBS, in this study, we first set up an in vivo .…”

Section: Introductionmentioning

confidence: 99%

“…Set the stimulation intensity to 200 μA. 16. Deliver an HFS for the desired period of time as set up.…”

mentioning

confidence: 99%

An Invasive Method for the Activation of the Mouse Dentate Gyrus by High-frequency Stimulation

Zhao¹,

Wu²

2018

JoVE

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Electrical high-frequency stimulation (HFS), using implanted electrodes targeting various brain regions, has been proven as an effective treatment for various neurological and psychiatric disorders. HFS in the deep region of the brain, also named deep-brain stimulation (DBS), is becoming increasingly important in clinical trials. Recent progress in the field of high-frequency DBS (HF-DBS) surgery has begun to spread the possibility of utilizing this invasive technique to other situations, such as treatment for major depression disorder (MDD), obsessive-compulsive disorder (OCD), and so on. Despite these expanding indications, the underlying mechanisms of the beneficial effects of HF-DBS remain enigmatic. To address this question, one approach is to use implanted electrodes that sparsely activate distributed subpopulations of neurons by HFS. It has been reported that HFS in the anterior nucleus of the thalamus could be used for the treatment of refractory epilepsy in the clinic. The underlying mechanisms might be related to the increased neurogenesis and altered neuronal activity. Therefore, we are interested in exploring the physiological alterations by the detection of neuronal activity as well as neurogenesis in the mouse dentate gyrus (DG) before and after HFS treatment. In this manuscript, we describe methodologies for HFS to target the activation of the DG in mice, directly or indirectly and in an acute or chronic manner. In addition, we describe a detailed protocol for the preparation of brain slices for c-fos and Notch1 immunofluorescent staining to monitor the neuronal activity and signaling activation and for bromodeoxyuridine (BrdU) labeling to determine the neurogenesis after the HF-DBS induction. The activation of the neuronal activity and neurogenesis after the HF-DBS treatment provides direct neurobiological evidence and potential therapeutic benefits. Particularly, this methodology can be modified and applied to target other interested brain regions such as the basal ganglia and subthalamic regions for specific brain disorders in the clinic.

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Effects of anterior thalamic nuclei stimulation on gene expression in a rat model of temporal lobe epilepsy

et al. 2019

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Analysis of Gene Expression Changes in the Rat Hippocampus After Deep Brain Stimulation of the Anterior Thalamic Nucleus

Cited by 7 publications

References 60 publications

The SANTÉ study at 10 years of follow‐up: Effectiveness, safety, and sudden unexpected death in epilepsy

The SANTÉ study at 10 years of follow‐up: Effectiveness, safety, and sudden unexpected death in epilepsy

An Invasive Method for the Activation of the Mouse Dentate Gyrus by High-frequency Stimulation

Effects of anterior thalamic nuclei stimulation on gene expression in a rat model of temporal lobe epilepsy

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