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In many countries, 400 units (U) is the maximum dose of onabotulinumtoxinA available to treat upper limb spasticity, but few studies have demonstrated the optimal use of this dose. In the double-blind phase of this randomized, controlled trial, we compared the efficacy and safety of 400 vs. 240 U onabotulinumtoxinA in patients with post-stroke upper limb spasticity. Both groups received 240 U onabotulinumtoxinA injected in the forearm. An additional 160 U onabotulinumtoxinA (400 U group) or placebo (240 U group) was injected in the elbow flexors. Both groups showed similar muscle tone reduction in the wrist, fingers, and thumb; muscle tone reduction in the elbow flexors was greater in the group treated with onabotulinumtoxinA (400 U group) compared to placebo (240 U group). Functional disabilities improved in both groups. No substantial difference was found in safety profiles. In the subsequent open-label phase, all participants received repeat injections of 400 U onabotulinumtoxinA (target muscles and doses per muscle determined by the physician). Similar efficacy and safety outcomes, as with the 400 U group in the double-blind phase, were confirmed. This final report demonstrates that injection of onabotulinumtoxinA 400 U relieves muscle tone in a wide range of areas and improves functional disabilities; generally, it was well-tolerated, and no new safety concerns were identified. The dosing data in the open-label phase will inform optimal use of onabotulinumtoxinA in clinical practice (ClinicalTrials.gov: NCT03261167).

Objectives: This study is a retrospective investigation of the effects of repetitive botulinum toxin A therapy (BoNT-A) and intensive rehabilitation (IR) on lower limb spasticity in post-stroke patients. Methods: Thirty-five post-stroke patients was included in this study and received BoNT-A for the first time. A 12-day inpatient protocol was with 4 cycles of the treatment protocol. The severity of spasticity, motor function and brace status were evaluated. Results: The modified Ashworth Scale (MAS) score of ankle dorsiflexors, range of motion, walking speed and balancing ability were significantly improved after cycle 1. The improvement of spasticity and motor function was persistent through cycles 2–4. One-third of brace users were able to discontinue the use of a brace. All of these brace users showed a forward gait pattern prior to therapy. Conclusions: Repeated BoNT-A combined with IR improved lower limb spasticity in post-stroke patients. Our results suggest that patients who show the forward gait pattern prior to therapy may be able to discontinue the use of their brace after therapy.

Abstract Aims Chronic stress and glucocorticoid exposure are risk factors for depression. Oxytocin (OT) has been shown to have antistress and antidepressant‐like effects in male rodents. However, depression is twice as common in women than in men, and it remains unclear whether OT exerts antidepressant‐like effects in women with depression. Therefore, in this study, we investigated the therapeutic effect of chronic OT administration in a female mouse model of dexamethasone (DEX)‐induced depression. Methods Female C57BL/6J mice were administered saline (vehicle, s.c.), DEX (s.c.), or OT (i.p.) + DEX (s.c.) daily for 8 weeks, and then assessed for anxiety‐ and depression‐like behaviors. We also examined the hippocampal levels of phosphorylated cAMP response element‐binding protein (p‐CREB) and brain‐derived neurotrophic factor (BDNF), which are important mediators of the response to antidepressants. Results Simultaneous OT treatment blocked the adverse effects of DEX on emotional behaviors. Furthermore, it upregulated p‐CREB and BDNF in the hippocampus. Conclusion OT may exert antidepressant‐like effects by activating hippocampal CREB‐BDNF signaling in a female mouse model of depression.

Background: Psychosocial stress factors, such as threat and defeat, are major risk factors for the development of depression. The precise mechanisms underlying stress-induced depression are not clearly understood because the stress response in the brain varies in a stress-frequency-dependent manner. In the current research milieu on the pathogenesis of depression, the focus is on depression-like behavioral phenotype, hypothalamic-pituitary-adrenal (HPA) axis, and hippocampal neurogenesis. However, most studies have evaluated the symptomatic features of depression at certain time points after exposure to psychosocial stress. Here, we examined the frequency-dependent effects of psychosocial stress on depression-related features in rats. Methods: In the present study, different frequencies (one, two, three, or four times) of psychosocial stress were applied to 19 male Sprague-Dawley rats using a resident/intruder paradigm. Subsequently, the rats were subjected to a stress reactivity test to evaluate HPA axis activity, following which assessments of immobility behavior in the forced swimming test (FST) and adult neurogenesis were conducted. Results: One-time stressed rats showed a decrease in immobility behavior in the FST and the amount of doublecortin (DCX)-positive cells. Two-time stress caused hypoactivity of the HPA axis. In contrast, immobility behavior and HPA axis activity were increased after four-time stress exposure, but the number of DCX-positive cells was decreased. Conclusions: Our findings suggest that psychosocial stress produces a biphasic effect on the symptoms of depression in a stress-frequency-dependent manner, which could provide insights to facilitate further pathogenesis research on depression.