Alzheimer’s disease (AD) is the most common type of dementia but lacks effective treatment at present. Gastrodin (GAS) is a phenolic glycoside extracted from the traditional Chinese herb—Gastrodia elata—and has been reported as a potential therapeutic agent for AD. However, its efficiency is reduced for AD patients due to its limited BBB permeability. Studies have demonstrated the feasibility of opening the blood-brain barrier (BBB) via focused ultrasound (FUS) to overcome the obstacles preventing medicines from blood flow into the brain tissue. We explored the therapeutic potential of FUS-mediated BBB opening combined with GAS in an AD-like mouse model induced by unilateral intracerebroventricular (ICV) injection of Aβ1-42. Mice were divided into 5 groups: control, untreated, GAS, FUS and FUS+GAS. Combined treatment (FUS+GAS) rather than single intervention (GAS or FUS) alleviated memory deficit and neuropathology of AD-like mice. The time that mice spent in the novel arm was prolonged in the Y-maze test after 15-day intervention, and the waste-cleaning effect was remarkably increased. Contents of Aβ, tau, and P-tau in the observed (also the targeted) hippocampus were reduced. BDNF, synaptophysin (SYN), and PSD-95 were upregulated in the combined group. Overall, our results demonstrate that FUS-mediated BBB opening combined with GAS injection exerts the potential to alleviate memory deficit and neuropathology in the AD-like experimental mouse model, which may be a novel strategy for AD treatment.

Effective treatment remains lacking for neuropathic pain (NP), a type of intractable pain. Low-intensity focused ultrasound (LIFU), a noninvasive, cutting-edge neuromodulation technique, can effectively enhance inhibition of the central nervous system (CNS) and reduce neuronal excitability. We investigated the effect of LIFU on NP and on the expression of potassium chloride cotransporter 2 (KCC2) in the spinal cords of rats with peripheral nerve injury (PNI) in the lumbar 4–lumbar 5 (L4–L5) section. In this study, rats received PNI surgery on their right lower legs followed by LIFU stimulation of the L4–L5 section of the spinal cord for 4 weeks, starting 3 days after surgery. We used the 50% paw withdraw threshold (PWT50) to evaluate mechanical allodynia. Western blotting (WB) and immunofluorescence (IF) were used to calculate the expression of phosphorylated extracellular signal–regulated kinase 1/2 (p-ERK1/2), calcium/calmodulin-dependent protein kinase type IV (CaMKIV), phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB), and KCC2 in the L4–L5 portion of the spinal cord after the last behavioral tests. We found that PWT50 decreased ( P < 0.05 ) 3 days post-PNI surgery in the LIFU− and LIFU+ groups and increased ( P < 0.05 ) after 4 weeks of LIFU stimulation. The expression of p-CREB and CaMKIV decreased ( P < 0.05 ) and that of KCC2 increased ( P < 0.05 ) after 4 weeks of LIFU stimulation, but that of p-ERK1/2 ( P > 0.05 ) was unaffected. Our study showed that LIFU could effectively alleviate NP behavior in rats with PNI by increasing the expression of KCC2 on spinal dorsal corner neurons. A possible explanation is that LIFU could inhibit the activation of the CaMKIV–KCC2 pathway.

Low-intensity focused ultrasound (LIFU) is a potential noninvasive method to alleviate allodynia by modulating the central nervous system. However, the underlying analgesic mechanisms remain unexplored. Here, we assessed how LIFU at the anterior cingulate cortex (ACC) affects behavior response and central plasticity resulting from chronic constrictive injury (CCI). The safety of LIFU stimulation was assessed by hematoxylin and eosin (H&E) and Fluoro-Jade C (FJC) staining. A 21-day ultrasound exposure therapy was conducted from day 91 after CCI surgery in mice. We assessed the 50% mechanical withdrawal threshold (MWT50) using Von Frey filaments (VFFs). The expression levels of microtubule-associated protein 2 (MAP2), growth-associated protein 43 (GAP43), and tau were determined via western blotting (WB) and immunofluorescence (IF) staining to evaluate the central plasticity in ACC. The regions of ACC were activated effectively and safely by LIFU stimulation, which significantly increased the number of c-fos-positive cells ( P < 0.05 ) with no bleeding, coagulative necrosis, and neuronal loss. Under chronic neuropathic pain- (CNP-) induced allodynia, MWT50 decreased significantly ( P < 0.05 ), and overexpression of MAP2, GAP43, and tau was also observed. After 3 weeks of treatment, significant increases in MWT50 were found in the CCI+LIFU group compared with the CCI group ( P < 0.05 ). WB and IF staining both demonstrated a significant reduction in the expression levels of MAP2, GAP43, and tau ( P < 0.05 ). LIFU treatment on ACC can effectively attenuate CNP-evoked mechanical sensitivity to pain and reverse aberrant central plasticity.

Background The International Scientific Society on Scoliosis Orthopedic and Rehabilitation Treatment (SOSORT) proposes that the effect of brace treatment combined with physiotherapeutic scoliosis-specific exercises is significantly better than that of either alone. Wearing full-time rigid braces 23 h a day can effectively control the progression of scoliosis. However, long-term wearing of braces can cause psychological disorders, dyskinesia, lung function disorders, and other issues. Nevertheless, exercise can increase muscle function, correct the physical line, and compensate for the side effects of orthotic treatment. Objective To explore the clinical effects of wearing a full-time rigid brace for 20–24 h/day compared to a part-time rigid brace for 14–18 h/day combined with Schroth three-dimensional exercises on scoliosis correction and quality of life in patients with adolescent idiopathic scoliosis (AIS). Methods Sixty AIS patients were randomly assigned to the full-time brace group and the part-time brace combined with Schroth exercise group, with 30 patients in each group. Patients in the full-time brace group were treated with a rigid thoracolumbar orthosis and were required to wear it for 20–23 h/d. Patients in the part-time brace combined with Schroth exercise group were treated with Schroth three-dimensional exercise, with home and outpatient training together at least 5 times per week. The weekly training time was at least 4–5 hours, and the orthotic device was worn for 14–18 h/d. The two groups of patients were evaluated for Cobb angles and the angle of trunk rotation (ATR), thoracic expansion, and scoliosis research society 22-item (SRS-22) patient questionnaire before enrollment and after 6 months of treatment. Results In the intragroup comparison, Cobb angles, ATR, and thoracic expansion were significantly improved in the combined treatment group after 6 months of treatment compared to before treatment (p < 0.01), and the four indices of SRS-22 were improved before and after treatment, but there was no significant difference (p > 0.05). In the full-time brace group, there was a significant reduction in the Cobb angles (P < 0.01), but there was no statistically significant difference in the ATR, thoracic expansion, or SRS-22 before and after treatment. Comparing between groups, the combined treatment group showed greater improvement in Cobb angles, ATR, thoracic expansion, and the items of pain and psychology in the SRS-22 compared to the full-time brace group (p < 0.05). There were no differences between the two groups in self-image and function on the SRS-22 (P > 0.05). The satisfaction survey in the SRS-22 of the combined treatment group was better than that of the brace group, but there was no significant difference (P > 0.05). Conclusion The full-time brace and the Schroth 3D motion combined with a part-time brace both decreased the Cobb angle in AIS patients after 6 months of treatment. In addition, the brace combined with Schroth exercise showed significant improvement in the ATR, thoracic expansion, and psychological status and relieved pain. Adequate Schroth exercise can appropriately reduce the time of brace wear without affecting clinical outcomes and support brace treatment. Therefore, conservative treatment of idiopathic scoliosis with bracing combined with Schroth 3D exercise is recommended.