RESUMEN
BACKGROUND: Treatment-refractory schizophrenia (TRS), accounting for approximately 30% of all schizophrenia cases, has poor treatment response and prognosis despite treatment with antipsychotic drugs. AIM: To analyze the therapeutic effectiveness of repetitive transcranial magnetic stimulation (rTMS) combined with olanzapine (OLZ) and amisulpride (AMI) for TRS and its influence on the patient's cognitive function. METHODS: This study enrolled 114 TRS patients who received treatment at the First Affiliated Hospital of Zhengzhou University between July 2019 and July 2022. In addition to the basic OLZ + AMI therapy, 54 cases of the control group (Con group) received modified electroconvulsive therapy, while 60 cases of the research group (Res group) received rTMS. Data on therapeutic effectiveness, safety (incidence of drowsiness, headache, nausea, vomiting, or memory impairment), Positive and Negative Symptom Scale, Montreal Cognitive Assessment Scale, and Schizophrenia Quality of Life Scale were collected from both cohorts for comparative analyses. RESULTS: The Res group elicited a higher overall response rate and better safety profile when compared with the Con group. Additionally, a significant reduction was observed in the post-treatment Positive and Negative Symptom Scale and Schizophrenia Quality of Life Scale scores of the Res group, presenting lower scores than those of the Con group. Furthermore, a significant increase in the Montreal Cognitive Assessment Scale score was reported in the Res group, with higher scores than those of the Con group. CONCLUSION: The treatment of TRS with rTMS and OLZ + AMI is effective and safe. Moreover, it can alleviate the patients' mental symptoms, improve their cognitive function and quality of life, and has a high clinical application value.
RESUMEN
BACKGROUND: Functional electrical stimulation (FES) is known to promote the recovery of motor function in rats with ischemia and to upregulate the expression of growth factors which support brain neurogenesis. In this study, we investigated whether postischemic FES could improve functional outcomes and modulate neurogenesis in the subventricular zone (SVZ) after focal cerebral ischemia. METHODS: Adult male Sprague-Dawley rats with permanent middle cerebral artery occlusion (MCAO) were randomly assigned to the control group, the placebo stimulation group, and the FES group. The rats in each group were further assigned to one of four therapeutic periods (1, 3, 7, or 14 days). FES was delivered 48 hours after the MCAO procedure and divided into two 10-minute sessions on each day of treatment with a 10-minute rest between them. Two intraperitoneal injections of bromodeoxyuridine (BrdU) were given 4 hours apart every day beginning 48 hours after the MCAO. Neurogenesis was evaluated by immunofuorescence staining. Wnt-3 which is strongly implicated in the proliferation and differentiation of neural stem cells (NSCs) was investigated by Western blotting analysis. The data were subjected to one- way analysis of variance (ANOVA), followed by a Tukey/Kramer or Dunnett post hoc test. RESULTS: FES significantly increased the number of BrdU-positive cells and BrdU/glial fibrillary acidic protein double- positive neural progenitor cells in the SVZ on days 7 and 14 of the treatment (P < 0.05). The number of BrdU/doublecortin (DCX) double-positive migrating neuroblast cells in the ipsilateral SVZ on day 14 of the FES treatment group ((522.77 ± 33.32) cells/mm(2)) was significantly increased compared with the control group ((262.58 ± 35.11) cells/mm(2), P < 0.05) and the placebo group ((266.17 ± 47.98) cells/mm(2), P < 0.05). However, only a few BrdU/neuron-specific nuclear protein-positive cells were observed by day 14 of the treatment. At day 7, Wnt-3 was upregulated in the ipsilateral SVZs of the rats receiving FES ((0.44 ± 0.05)%) compared with those of the control group rats ((0.31 ± 0.02)%, P < 0.05) or the placebo group rats ((0.31 ± 0.04)%, P < 0.05). At day 14, the corresponding values were (0.56 ± 0.05)% in the FES group compared with those of the control group rats ((0.50 ± 0.06)%, P < 0.05) or the placebo group rats ((0.48 ± 0.06)%, P < 0.05). CONCLUSION: FES augments the proliferation, differentiation, and migration of NSCs and thus promotes neurogenesis, which may be related to the improvement of neurological outcomes.