Subthalamic nucleus lesion improves cell survival and functional recovery following dopaminergic cell transplantation in parkinsonian rats

Cordeiro, Karina Kohn; Cordeiro, Joacir Graciolli; Furlanetti, Luciano; Garcia, Salazar Joanna Alejandra; Tenório, Sérgio Bernardo; Winkler, Christian; Döbrössy, Máté; Nikkhah, Guido

doi:10.1111/ejn.12541

Cited by 12 publications

(11 citation statements)

References 79 publications

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“…This neurodegenerative effect could be prevented by prior lesioning of the STN, suggesting that it was likely mediated by increased STN activity because of loss of GABA‐ergic tone from the GPe . More recently, partial subthalamotomy was shown to improve cell survival following dopaminergic cell transplantation in 6‐OHDA‐lesioned rats, and the neuroprotective effect of subthalamotomy was confirmed in MPTP‐treated monkeys . Admittedly, the results of these experiments are not universally positive, that is, a neuroprotective effect shown, but a large majority of both rodent and monkey studies have shown a neuroprotective effect (Table ), which could not be judged as minor.…”

Section: The Subthalamic Nucleus As a Target To Halt Neurodegeneratiomentioning

confidence: 99%

Focused ultrasound in Parkinson's disease: A twofold path toward disease modification

et al. 2019

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A major unmet need in Parkinson's disease (PD) is to slow the inexorable progression of neurodegeneration. Clinical trials that evaluated promising pharmacological strategies have repeatedly failed. Nonetheless, the advent of focused ultrasound provides new opportunities toward the goal of developing a safe and effective disease‐modifying therapy for PD. Here we discuss the rationale, possible avenues, and challenges along this path, exploiting the potential of focused ultrasound for (1) performing focal thermal lesions to restore the basic basal ganglia abnormalities associated with dopamine depletion, and (2) transiently opening the blood–brain barrier for targeted delivery of therapeutic agents. First, the classic idea of excitotoxicity mediated by hyperactivity of the subthalamic nucleus suggests that focused ultrasound subthalamotomy may offer a clinically viable disease‐modifying therapy in very‐early PD. Second, the concept of retrograde nigrostriatal neurodegeneration, supported by our recent cortical pathogenic theory of PD, points toward the putamen as a principal site for focused ultrasound blood–brain barrier opening and targeted drug delivery. In principle, both therapeutic strategies—subthalamotomy and putaminal blood–brain barrier opening—could eventually be applied in the same patient. Clinical application is still a long road ahead; nevertheless, focused ultrasound may open a twofold path toward disease modification in PD. © 2019 International Parkinson and Movement Disorder Society

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Section: The Subthalamic Nucleus As a Target To Halt Neurodegeneratiomentioning

confidence: 99%

Focused ultrasound in Parkinson's disease: A twofold path toward disease modification

et al. 2019

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“…Forelimb movement asymmetry and exploratory behavior were tested with the cylinder test (Schallert et al 2000 ; Cordeiro et al 2014 ) following MFB lesion (BL) and in the other sessions indicated above. The animals were placed in the center of a 20-cm-diameter clear Plexiglas cylinder, and their exploratory behavior was recorded with a camera for 4 min.…”

Section: Methodsmentioning

confidence: 99%

Chronic deep brain stimulation of the medial forebrain bundle reverses depressive-like behavior in a hemiparkinsonian rodent model

Furlanetti¹,

Coenen²,

Aranda³

et al. 2015

Exp Brain Res

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Preclinical and clinical evidence suggests that depression might be associated with a dysfunction in the reward/motivation circuitry. Deep brain stimulation (DBS) of the superolateral branch of the medial forebrain bundle (MFB) has been shown in a recent clinical trial to provide a prompt and consistent improvement of depressive symptoms in treatment-resistant patients. In order to better understand the underlying mechanisms of neuromodulation in the context of depression, the effects of chronic bilateral MFB-DBS were assessed in a combined rodent model of depression and Parkinson’s disease. Female Sprague-Dawley rats received unilateral 6-OHDA injection in the right MFB and were divided into three groups: CMS-STIM, CMS-noSTIM and control group. The CMS groups were submitted to chronic unpredictable mild stress (CMS) protocol for 6 weeks. MFB-DBS was applied only to the CMS-STIM group for 1 week. All groups were repeatedly probed on a series of behavioral tasks following each intervention, and to a postmortem histological analysis. CMS led to an increase in immobility in the forced swim test, to a decrease in sucrose solution consumption in the sucrose preference test, as well as to an increased production of ultrasonic vocalizations in the 22 kHz range, indicating increased negative affect. MFB-DBS reversed the anhedonic-like and despair-like behaviors. The results suggest that unilateral dopamine depletion did not preclude MFB-DBS in reversing depressive-like and anhedonic-like behavior in the rodent. Further understanding of the importance of hemispheric dominance in neuropsychiatric disorders is essential in order to optimize stimulation as a therapeutic strategy in these diseases.

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“…After ED-1-DAB staining, sections were double-stained for Hematoxylin & Eosin (H&E), using a standard protocol. The sections were mounted on super frost plus slides (Langenbrinck, Emmendingen, Germany), dehydrated in ascending alcohol solutions, and cleared in xylene before they were cover slipped with Histofluid (Marienfeld Laborglas, Lauda-Königshofen, Germany) [ 25 ].…”

Section: Methodsmentioning

confidence: 99%

Feasibility and Safety of Continuous and Chronic Bilateral Deep Brain Stimulation of the Medial Forebrain Bundle in the Naïve Sprague-Dawley Rat

Furlanetti

Döbrössy

Aranda

et al. 2015

Behavioural Neurology

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Objective. Deep brain stimulation (DBS) of the superolateral branch of the medial forebrain bundle (MFB) has provided rapid and dramatic reduction of depressive symptoms in a clinical trial. Early intracranial self-stimulation experiments of the MFB suggested detrimental side effects on the animals' health; therefore, the current study looked at the viability of chronic and continuous MFB-DBS in rodents, with particular attention given to welfare issues and identification of stimulated pathways. Methods. Sprague-Dawley female rats were submitted to stereotactic microelectrode implantation into the MFB. Chronic continuous DBS was applied for 3–6 weeks. Welfare monitoring and behavior changes were assessed. Postmortem histological analysis of c-fos protein expression was carried out. Results. MFB-DBS resulted in mild and temporary weight loss in the animals, which was regained even with continuing stimulation. MFB-DBS led to increased and long-lasting c-fos expression in target regions of the mesolimbic/mesocortical system. Conclusions. Bilateral continuous chronic MFB-DBS is feasible, safe, and without impact on the rodent's health. MFB-DBS results in temporary increase in exploration, which could explain the initial weight loss, and does not produce any apparent behavioral abnormalities. This platform represents a powerful tool for further preclinical investigation of the MFB stimulation in the treatment of depression.

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Subthalamic nucleus lesion improves cell survival and functional recovery following dopaminergic cell transplantation in parkinsonian rats

Cited by 12 publications

References 79 publications

Focused ultrasound in Parkinson's disease: A twofold path toward disease modification

Focused ultrasound in Parkinson's disease: A twofold path toward disease modification

Chronic deep brain stimulation of the medial forebrain bundle reverses depressive-like behavior in a hemiparkinsonian rodent model

Feasibility and Safety of Continuous and Chronic Bilateral Deep Brain Stimulation of the Medial Forebrain Bundle in the Naïve Sprague-Dawley Rat

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