Journal: Journal of Neurosurgery

Article Title: Motor speech effects in subthalamic deep brain stimulation for Parkinson’s disease

doi: 10.3171/2021.12.JNS211729

Figure Lengend Snippet: Distinct stimulation sites for dysarthria and motor improvement. Average volumes of tissue activation for maximal MDS-UPDRS motor improvement (green) and dysarthria worsening (red). DBS electrode shown with the STN (yellow), substantia nigra (purple), and internal capsule (blue fibers). A = anterior; D = dorsal; L = lateral. Figure is available in color online only.

Article Snippet: Stage I surgery involved bilateral implantation of STN DBS electrodes (model 3389, Medtronic Inc.) with microelectrode recording.

Techniques: Activation Assay

Journal: Movement Disorders

Article Title: BDNF provides many routes toward STN DBS‐mediated disease modification

doi: 10.1002/mds.27535

Figure Lengend Snippet: Timing of nigrostriatal degeneration (adapted from Kordower et al [2013] . Average time course for degeneration since diagnosis of PD ( x axis) is plotted for both putaminal TH immunoreactivity (left y axis, red line) and number of melanized neurons in the substantia nigra (right y axis, black line) compared with the average from age‐matched controls (dashed line). The gray box brackets the window during which the majority of trials examining STN DBS have occurred (compare with Table ). For illustration, points A, B, C, D, and E correspond to the studies conducted by Charles et al, Schuepbach et al, Tagliati et al, Hilker et al, and Pal et al, , respectively.

Article Snippet: Rocha et al (2014) , 60 (8) , 14 (range, 5‐48) , None , N/A , Survival of 99% and 94% at 3 and 5 years, respectively, with DBS (mixed GPi and STN)..

Techniques: Biomarker Discovery

Journal: Movement Disorders

Article Title: BDNF provides many routes toward STN DBS‐mediated disease modification

doi: 10.1002/mds.27535

Figure Lengend Snippet: Clinical trials assessing STN DBS

Article Snippet: Rocha et al (2014) , 60 (8) , 14 (range, 5‐48) , None , N/A , Survival of 99% and 94% at 3 and 5 years, respectively, with DBS (mixed GPi and STN)..

Techniques: Clinical Proteomics, Control, Binding Assay

Journal: Movement Disorders

Article Title: BDNF provides many routes toward STN DBS‐mediated disease modification

doi: 10.1002/mds.27535

Figure Lengend Snippet: Predictive validity of preclinical models for STN DBS‐mediated neuroprotection (adapted from Spieles‐Engemann et al [2010] 136

Article Snippet: Rocha et al (2014) , 60 (8) , 14 (range, 5‐48) , None , N/A , Survival of 99% and 94% at 3 and 5 years, respectively, with DBS (mixed GPi and STN)..

Techniques: Phospho-proteomics, Over Expression

Journal: Movement Disorders

Article Title: BDNF provides many routes toward STN DBS‐mediated disease modification

doi: 10.1002/mds.27535

Figure Lengend Snippet: STN DBS increases BDNF in the basal ganglia in PD animal models. Coronal sections of select basal ganglia structures in the rat are depicted in 3 dimensions relative to one another, and an electrode stimulating the STN is illustrated. Effects of high‐frequency stimulation of the STN on BDNF levels in the rat are noted. STN DBS increases BDNF mRNA in the SN and entopeduncular nucleus (EP, rodent homologue to primate GPi). STN DBS also increases BDNF protein in the primary motor cortex (M1) and the striatum of unlesioned animals and the SN of lesioned animals. The green arrow represents dopaminergic fibers; the black arrows represent glutamatergic fibers. Data summarized from Spieles‐Engemann et al (2011).

Article Snippet: Rocha et al (2014) , 60 (8) , 14 (range, 5‐48) , None , N/A , Survival of 99% and 94% at 3 and 5 years, respectively, with DBS (mixed GPi and STN)..

Techniques:

Journal: Movement Disorders

Article Title: BDNF provides many routes toward STN DBS‐mediated disease modification

doi: 10.1002/mds.27535

Figure Lengend Snippet: Hypothetical routes for BDNF‐mediated disease modification. Preclinical studies have demonstrated STN DBS‐mediated neuroprotection in rodents and nonhuman primates. , , , , , In addition, high‐frequency stimulation increases BDNF in vitro and in vivo. , , , , In light of these preclinical studies, there are several hypothetical routes for BDNF‐mediated disease modification. The SNpc may be protected directly (A,B). , , , , , , (A) DBS increases STN activity, increases activity‐dependent release of BDNF at the SNpc and binding to TrkB for a trophic effect. (B) DBS increases STN activity, increases glutamate (Glu) release at the SNpc and binding to NMDA receptors (NMDAR). SNpc activation results in production of BDNF transcript, translation, and local release of BDNF that binds to TrkB for an autocrine/paracrine trophic effect. BDNF may maintain striatal spine density and facilitate dopamine transmission (C,D). , , , , , , (C) DBS increases STN activity, increases glutamate (Glu) release at the SNpc and binding to NMDA receptors (NMDAR). SNpc activation results in production of BDNF transcript, translation, and activity‐dependent release of BDNF that binds to TrkB on striatal medium spiny neurons (MSNs) for a trophic effect, including maintenance of spine density. (D) DBS results in antidromic activation of corticosubthalamic projections from the motor cortex (M1) and subsequent activity‐dependent release of BDNF via corticostriatal fibers to bind to TrkB on MSNs for an ultimately trophic effect. BDNF may enhance M1 plasticity (E,F). , , (E) DBS results in antidromic activation of corticosubthalamic projections from the M1 and activity‐dependent release of BDNF by cortical neurons in an autocrine/paracrine manner, thereby enhancing plasticity. (F) DBS activates STN activity and through subthalamocortical projections found in the rat releases BDNF in the M1 and enhancing plasticity. Of importance, BDNF‐trkB signaling exerts powerful effects on intracellular signaling pathways (G). , , , , (G) Intraneuronal changes with some shown in the STN DBS paradigm specifically, where TrkB phosphorylation results in phosphorylation of Akt and ribosomal protein S6 (rpS6), as well as MAPK/Erk and PLCγ/cAMP signaling pathways that have been shown to result in changes in transcription, translation, and protein transport.

Article Snippet: Rocha et al (2014) , 60 (8) , 14 (range, 5‐48) , None , N/A , Survival of 99% and 94% at 3 and 5 years, respectively, with DBS (mixed GPi and STN)..

Techniques: Modification, In Vitro, In Vivo, Activity Assay, Binding Assay, Activation Assay, Transmission Assay, Protein-Protein interactions, Phospho-proteomics