Effect of Functional Electrical Stimulation in Convalescent Stroke Patients: A Multicenter, Randomized Controlled Trial.

BACKGROUND: We evaluated whether the Walkaide® device could effectively improve walking ability and lower extremity function in post-stroke patients with foot drop. Patients aged 20-85 years with an initial stroke within ≤6 months and a functional ambulation classification score of 3 or 4 were eligible. MATERIALS AND METHODS: Patients were randomly allocated to the functional electrical stimulation (FES) or control group at a 1:1 ratio. A 40 min training program using Walkaide was additionally performed by the FES group five times per week for 8 weeks. The control group received the 40 min training program without FES. RESULTS: A total of 203 patients were allocated to the FES (n = 102) or control (n = 101) groups. Patients who did not receive the intervention or whose data were unavailable were excluded. Finally, the primary outcome data of 184 patients (n = 92 in each group) were analyzed. The mean change in the maximum distance during the 6-MWT (primary outcome) was 68.37 ± 62.42 m and 57.50 ± 68.17 m in the FES and control groups (difference: 10.86 m; 95% confidence interval: -8.26 to 29.98, p = 0.26), respectively. CONCLUSIONS: In Japanese post-stroke patients with foot drop, FES did not significantly improve the 6 min walk distance during the convalescent phase. The trial was registered at UMIN000020604.

Quantitative imaging of spontaneous neuromagnetic activity for assessing cerebral ischemia using sLORETA-qm.

To image cerebral neural activity in ischemic areas, we proposed a novel technique to analyze spontaneous neuromagnetic fields based on standardized low-resolution brain electromagnetic tomography modified for a quantifiable method (sLORETA-qm). Using a 160-channel whole-head-type magnetoencephalographic system, cerebral magnetic fields were obtained pre- and postoperatively from 5 patients with unilateral internal carotid artery occlusive disease and 16 age-matched healthy volunteers. For quantitative imaging, voxel-based time-averaged intensities of slow waves in 4 frequency bands (0.3-2 Hz, 2-4 Hz, 4-6 Hz and 6-8 Hz) were obtained by the proposed technique based on sLORETA-qm. Positron emission tomography with (15)O gas inhalation ((15)O-PET) was also performed in these patients to evaluate cerebral blood flow and metabolism. In all 5 patients, slow waves in every frequency band were distributed in the area of cerebrovascular insufficiency, as confirmed by (15)O-PET preoperatively. In 4 patients, slow-wave intensities in theta bands (4-6 Hz, 6-8 Hz) decreased postoperatively along with improvements in cerebral blood flow and metabolism, whereas delta bands (0.3-2 Hz, 2-4 Hz) showed no significant differences between pre- and postoperatively. One patient with deterioration of cerebral infarction after surgery showed marked increases in slow-wave intensities in delta bands (0.3-2 Hz, 2-4 Hz) postoperatively, with distribution close to the infarct region. The proposed quantitative imaging of spontaneous neuromagnetic fields enabled clear visualization and alternations of cerebral neural conditions in the ischemic area. This technique may offer a novel, non-invasive method for identifying cerebral ischemia, although further studies in a larger number of patients are warranted.

Histone deacetylase inhibitor, FK228, induces apoptosis and suppresses cell proliferation of human glioblastoma cells in vitro and in vivo.

We investigated the effects of FK228 on cell proliferation and apoptosis against human glioblastoma (GM) T98G, U251MG, and U87MG cells. Upon exposure to FK228, cell proliferation was inhibited, and apoptosis detected by the cleavage of CPP32 was induced. FK228 increased the expression levels of p21 (WAF-1) and of pro-apoptotic Bad protein in all GM cells. Furthermore, FK228 treatment also reduced the anti-apoptotic protein Bcl-xL in all GM cells and anti-apoptotic Bcl-2 in U87MG cells, thereby shifting the cellular equilibrium from life to death. An increased accumulation of histone H4 was detected in the p21 (WAF-1) promoter and the structural gene (exon 2) and the Bad structural gene (exon 2 and 3) upon treatment with FK228, as assessed by chromatin immunoprecipitation (ChIP) assay. Thus, the results indicated that an increased expression of p21 (WAF1) and Bad due to FK228 is regulated, at least in part, by the degree of acetylation of the gene-associated histone. We also found that FK228 inhibits cellular invasiveness and decreases MMP-2 activity. In addition, the growth of transplanted human GM m-3 cells into the subcutaneous tissue of hereditary athymic mice was significantly inhibited, and apoptosis was induced with FK228 treatment. The results suggested that FK228 might be useful in the treatment of human GM, although further studies will be needed.

Histone deacetylase inhibitors such as sodium butyrate and trichostatin A inhibit vascular endothelial growth factor (VEGF) secretion from human glioblastoma cells.

We investigated the effects of histone deacetylase (HDAC) inhibitors such as sodium butyrate (SB) and trichostatin A (TSA) on the expression of vascular endothelial growth factor (VEGF) by human glioblastoma T98G, U251MG, and U87MG cells. The glioblastoma cells secreted three VEGF isoforms, VEGF (189), (165), and (121), although the expression levels of VEGF differed between the cell types. Treatment with either 5mM SB or 100 ng/ml TSA reduced VEGF secretion in conditioned media and reduced VEGF mRNA expression. We also studied the expression of VEGF-B, -C, and -D mRNA in human glioblastoma cells and their modulation by HDAC inhibitors. The PCR products of VEGF-B (357bp), VEGF-C (501bp), and VEGF-D (484bp) were amplified in all glioblastoma cells examined. Treatment with SB reduced the expression of VEGF-D mRNA in U251MG cells and the expression of VEGF-B mRNA in U87MG cells. TSA treatment reduced the expression of VEGF-D in U251MG cells. These results suggest that HDAC inhibitors reduce VEGF secretion and modulate the expression of the other VEGF family members, and therefore may inhibit angiogenesis in glioblastoma tissues.