Data_Sheet_1_Rescue subthalamic stimulation after unsatisfactory outcome of pallidal stimulation in Parkinson's disease: a case series and review.PDF

BackgroundSubthalamic nucleus (STN) and globus pallidus interna (GPi) are two main structures primarily targeted by deep brain stimulation (DBS) to treat advanced Parkinson's disease (PD). A subset of cases with unsatisfactory outcomes may benefit from rescue DBS surgery targeting another structure, while these patients' characteristics have not been well described and this phenomenon has not been well reviewed.MethodsThis monocentric retrospective study included patients with PD, who underwent rescue STN DBS following an unsatisfactory outcome of the initial bilateral GPi DBS in a retrospective manner. A short review of the current literature was conducted to report the clinical outcome of rescue DBS surgeries.ResultsEight patients were identified, and six of them were included in this study. The rescue STN DBS was performed 19.8 months after the initial GPi DBS. After 8.8 months from the rescue STN DBS, patients showed a significant off-medication improvement by 29.2% in motor symptoms compared to initial GPi DBS. Non-motor symptoms and the health-related quality of life were also significantly improved.ConclusionOur findings suggest that the rescue STN DBS may improve off-medication motor and non-motor symptoms and quality of life in patients with failure of initial GPi DBS. The short review of the current literature showed that the target switching from GPi to STN was mainly due to poor initial outcomes and was performed by target substitution, whereas the switching from STN to GPi was mainly due to a gradual waning of benefits, long-term axial symptoms, dyskinesia, and dystonia and was performed by target addition.</p

GSK621 activates AMPK to inhibit mTOR and downregulate Tspan8 in human glioma cells.

<p>U87MG cells were either left untreated (“C”) or stimulated with GSK621 (25 μM) for applied periods of time, expressions of listed proteins were tested by Western blots (<b>A</b> and <b>B</b>). Stable U87MG cells with scramble control shRNA (“scr shRNA”), AMPKα shRNA (“-a”) or dominant negative AMPKα (T172A, “DN-AMPK”) were treated with GSK621 (25 μM) for indicated periods of time, expressions of listed proteins were tested by Western blots (<b>C</b> and <b>D</b>). Indicated protein expression was quantified. Experiments in this figure were repeated three times, and similar results were obtained.</p

GSK621 inhibits human glioma cell survival.

<p>Human glioma U87MG cells (A-C) and U251MG cells (D), as well as HCN-1a neuronal cells (D) or primary human astrocytes (“Astrocytes”, D) were either left untreated (“C”) or treated with applied concentrations of GSK621 for indicated periods of time, cell survival was tested by MTT assay (A and D) and clonogenicity assay (B); Cell death was also tested by the trypan blue staining assay (C). Experiments in this figure were repeated four times, and similar results were obtained. Data were presented as mean ± SD. * p <0.05 vs. “C”.</p

GSK621 provokes apoptosis in human glioma cells.

<p>Human glioma U87MG cells (A-E) and U251MG cells (F), as well as primary human astrocytes (“Astrocytes”, F) were either left untreated (“C”) or treated with applied concentrations of GSK621 for indicated periods of time, cell apoptosis was tested by listed assays (A-D, F); For D and E, cells were also pre-treated for 1 hour with the caspase-3 inhibitor z-DEVD-cho (50 μM) or the pan caspase inhibitor zVAD-cho (50 μM), and cell viability (E) was tested as well. Experiments in this figure were repeated three times, and similar results were obtained. Data were presented as mean ± SD. * p <0.05 vs. “C”. ^<b>#</b> p <0.05 vs. “GSK621” (D and E).</p

GSK621 sensitizes temozolomide-induced anti-glioma cell activity.

<p>U87MG cells (A-C) and U251MG cells (D), as well as primary human astrocytes (E, “Astrocytes”) were treated with temozolomide (“TMZ”, 100 μM) or plus GSK621 (“GSK”, 10 μM) for indicated periods of time, cell survival (A, D and E), cell death (B) and apoptosis (C) were tested by listed assays. Experiments in this figure were repeated three times, and similar results were obtained. Data were presented as mean ± SD. * p <0.05 vs. “C”. ^<b>#</b> p <0.05 vs. “TMZ” only.</p

AMPK activation is required for GSK621-induced cytotoxicity in human glioma cells.

<p>U87MG cells were either left untreated (“C”) or treated with applied concentrations of GSK621 for 2 hours, phospho- (p-) and regular ACC expressions were tested by Western blots (A). Scramble control shRNA (“scr shRNA”) or AMPKα shRNA (“no.1 or no.2”) expressing stable U87MG cells were treated with GSK621 (25 μM) for applied periods of time, AMPKα and ACC expressions were tested by Western blots (B); Cell survival (C, MTT assay) and apoptosis (D, Histone DNA ELISA assay) were also tested. Stable U87MG cells expressing a dominant negative AMPKα (T172A, “DN-AMPK”) or the empty vector (“Vector”) were treated with GSK621 (25 μM) for applied periods of time, AMPKα and ACC expressions were tested by Western blots (E); Cell survival (F, MTT assay) was also tested. U87MG cells were treated with AICAR (1 mM) or plus GSK621 (25 μM), cell viability (G, MTT assay, 72 hours) and apoptosis (H, Histone DNA ELISA assay, 36 hours) were tested. “Trans” stands for transfection reagents control (C and D). “C cells” stands for “non-transfected control cells” (F). Experiments in this figure were repeated three times, and similar results were obtained. Data were presented as mean ± SD. * p <0.05 vs. “C”. p-ACC (vs. Total ACC) was quantified. ^<b>#</b> p <0.05 vs. “scr shRNA” (C and D) or “Vector” (F).</p