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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The neural response to deep brain stimulation of the anterior nucleus of the thalamus: A MEMRI and c-Fos study

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Author(s):
Gimenes, Christiane [1] ; Malheiros, Jackeline Moraes [1] ; Battapady, Harsha [2] ; Tannus, Alberto [3] ; Hamani, Clement [4] ; Covolan, Luciene [1, 5]
Total Authors: 6
Affiliation:
[1] Univ Fed Sao Paulo, Dept Physiol, Sao Paulo - Brazil
[2] Renovo Neural Inc, Cleveland, OH - USA
[3] Univ Sao Paulo, Phys Inst Sao Carlos, Sao Paulo - Brazil
[4] Univ Toronto, Harquail Ctr Neuromodulat, Sunnybrook Hlth Sci Ctr, Toronto, ON - Canada
[5] Cleveland Clin, Neurol Inst, Epilepsy Ctr, Cleveland, OH 44106 - USA
Total Affiliations: 5
Document type: Journal article
Source: Brain Research Bulletin; v. 147, p. 133-139, APR 2019.
Web of Science Citations: 0
Abstract

Background: Deep brain stimulation (DBS) refers to the delivery of electric current to specific deep brain structures through implanted electrodes. Recently approved for use in United States, DBS to the anterior nucleus of thalamus (ANT) is a safe and effective alternative treatment for medically refractory seizures. Despite the anti-seizure effects of ANT DBS, preclinical and clinical studies have failed to demonstrate it actions at a whole brain level. Objective: Here, we used a magnetic resonance imaging (MRI)-based approach in healthy adult rats to investigate the effects of ANT DBS through the circuit of Papez, which has central role in the generation and propagation of limbic seizures, in temporal lobe epilepsy (TLE). Methods: After ANT electrode implantation and recovery, ANT DBS and SHAM (sham animals had electrodes implanted but were not stimulated) rats received one single injection of the contrast enhancer, manganese chloride (60 mg/kg, ip). Twelve hours after, rats underwent the baseline scan using the MEMRI (Manganese-Enhanced Magnetic Resonance Imaging) technique. We used the same MEMRI and parvalbumin sequence to follow the DBS delivered during 1 h (130 Hz and 2001 mu A). Perfusion was followed by subsequent c-Fos and parvalbumin immunostaining of brain sections. Results: Acute unilateral ANT DBS significantly reduced the overall manganese uptake and consequently, the MEMRI contrast in the circuit of Papez. Additionally, c-Fos expression was bilaterally increased in the cingulate cortex and posterior hypothalamus, areas directly connected to ANT, as well as in amygdala and subiculum, within the limbic circuitry. Conclusion: Our data indicate that MEMRI can be used to detect whole-brain responses to DBS, as the high frequency stimulation parameters used here caused a significant reduction of cell activity in the circuit of Papez that might help to explain the antiepileptic effects of ANT DBS. (AU)

FAPESP's process: 05/56663-1 - Magnetic resonance imaging and in vivo spectroscopy center for animal model studies
Grantee:Alberto Tannús
Support Opportunities: Inter-institutional Cooperation in Support of Brain Research (CINAPCE) - Thematic Grants