Transcutaneous auricular vagus nerve stimulation for post-stroke depression: A double-blind, randomized, placebo-controlled trial.

BACKGROUND: It is a well-established fact that post-stroke depression (PSD) is a prevalent condition that affects a significant proportion of individuals who have suffered a stroke. Hence, our research endeavors to explore the safety, efficacy and the potential molecular mechanism of transcutaneous auricular vagus nerve stimulation (ta-VNS) for the treatment of depression in PSD patients by conducting a double-blind, sham-controlled, randomized trial. METHODS: Patients who had experienced strokes and exhibited depressive symptoms, with a Hamilton Depression Scale (HAMD-17) score of ≥8 and met the DSM-IV criteria, were diagnosed with PSD. A volunteer sample of participants (N = 80) were randomly divided into either the ta-VNS group (which received ta-VNS in addition to conventional treatment) or the control group (which received conventional treatment only), in a 1:1 ratio. The effectiveness of the interventions was evaluated using the 17-item Hamilton Rating Scale for Depression (HAMD-17), Zung Self-Rating Depression Scale (SDS), and Barthel Index (BI) scores. Furthermore, Plasma BDNF, CREB1, and 5-HT levels were measured before and after treatment. RESULTS: The concomitant application of ta-VNS demonstrated a remarkable reduction in HAMD-17 and SDS scores, leading to noteworthy enhancements in patients' daily functioning, as evidenced by improved activities of daily living, at all assessed time points, in contrast to the control group (p < 0.0001). Notably, the ta-VNS group exhibited superior effects in modulating the measured neurotrophic biomarkers when compared to the control group (p < 0.05). CONCLUSIONS: The synergistic approach of combining ta-VNS with conventional treatment has demonstrated remarkable efficacy and tolerability in managing depression following a stroke.

Tryptophan metabolism as bridge between gut microbiota and brain in chronic social defeat stress-induced depression mice.

Backgrounds: Gut microbiota plays a critical role in the onset and development of depression, but the underlying molecular mechanisms are unclear. This study was conducted to explore the relationships between gut microbiota and host's metabolism in depression. Methods: Chronic social defeat stress (CSDS) model of depression was established using C57BL/6 male mice. Fecal samples were collected from CSDS group and control group to measure gut microbiota and microbial metabolites. Meanwhile, tryptophan metabolism-related metabolites in hippocampus were also analyzed. Results: CSDS successfully induced depressive-like behaviors in CSDS group. The 24 differential bacterial taxa between the two groups were identified, and 14 (60.87%) differential bacterial taxa belonged to phylum Firmicutes. Functional analysis showed that tryptophan metabolism was significantly affected in CSDS mice. Meanwhile, 120 differential microbial metabolites were identified, and two key tryptophan metabolism-related metabolites (tryptophan and 5-hydroxytryptophan (5-HTP)) were significantly decreased in feces of CSDS mice. The correlation analysis found the significant relationships between tryptophan and differential bacterial taxa under Firmicutes, especially genus Lactobacillus (r=0.801, p=0.0002). In addition, the significantly decreased 5-hydroxytryptamine (5-HT) in hippocampus of depressed mice was also observed. Conclusions: Our results showed that tryptophan metabolism might have an important role in the crosstalk between gut microbioa and brain in depression, and phylum Firmicutes, especially genus Lactobacillus, might be involved in the onset of depression through regulating tryptophan metabolism.

Long-term intermittent fasting improves neurological function by promoting angiogenesis after cerebral ischemia via growth differentiation factor 11 signaling activation.

Intermittent fasting (IF), an alternative to caloric restriction, is a form of time restricted eating. IF conditioning has been suggested to have neuroprotective effects and potential long-term brain health benefits. But the mechanism underlying remains unclear. The present study focused on the cerebral angiogenesis effect of IF on ischemic rats. Using a rat middle cerebral artery occlusion model, we assessed neurological outcomes and various vascular parameters such as microvessel density (MVD), regional cerebral blood flow (rCBF), proliferation of endothelial cells (ECs), and functional vessels in the peri-infarct area. IF conditioning ameliorated the modified neurological severity score and adhesive removal test, increased MVD, and activated growth differentiation factor 11 (GDF11)/activin-like kinase 5 (ALK5) pathways in a time-dependent manner. In addition, long-term IF conditioning stimulated proliferation of ECs, promoted rCBF, and upregulated the total vessel surface area as well as the number of microvessel branch points through GDF11/ALK5 pathways. These data suggest that long-term IF conditioning improves neurological outcomes after cerebral ischemia, and that this positive effect is mediated partly by angiogenesis in the peri-infarct area and improvement of functional perfusion microvessels in part by activating the GDF11/ALK5 signaling pathway.

Effect of transcutaneous auricular vagus nerve stimulation on post-stroke dysphagia.

BACKGROUND AND PURPOSE: It has been proved that electrical vagus nerve stimulation can promote the recovery of motor function after stroke. There were no trials on the use of transcutaneous auricular electrical vagus nerve stimulation (ta-VNS) in patients with dysphagia after acute stroke. Our aim was to confirm whether ta-VNS can promote the recovery of swallowing function in these acute stroke patients with dysphagia. METHODS: We conducted a sham-controlled, double-blinded, parallel pilot study in 40 acute stroke patients randomly assigned to receive ta-VNS or sham ta-VNS combined with conventional rehabilitation training. The intensity of ta-VNS treatment was adjusted according to the patient's tolerance, 30 min each time, twice a day, five times a week, with a total course of 3 weeks. In the sham group, the parameters were the same except energy output. Swallowing function was assessed with Modified Mann assessment of swallowing ability (MASA), functional communication measure swallowing test (FCM), and the Rosenbek leakage/aspiration scale (RAS) according to swallowing video fluoroscopic (SVF) before the intervention (baseline, T0), immediately after the intervention (T1) and 4 weeks after the intervention (T2). RESULTS: After treatment, ta-VNS group statistically and clinically had larger change of MASA, FCM, and RAS scores compared with control group (P < 0.05) and this improvement continued at least 4 weeks after the end of treatment. There were no serious adverse events occurred during the whole intervention. CONCLUSION: The transcutaneous auricular electrical vagus nerve stimulation is effective as a novel and noninvasive treatment strategy for patients with dysphagia after acute stroke. TRIAL REGISTRATION: No: kelunshen No. 63 in 2020.

Effect of Repetitive Transcranial Magnetic Stimulation on Post-stroke Dysphagia in Acute Stage.

Repetitive transcranial magnetic stimulation (rTMS) play a important role for rehabilitation in stroke. But therapeutic schedule of rTMS in dysphagia after acute stroke is still controversial. The purpose of this study was to investigate the therapeutic effect of rTMS with different frequencies on dysphagia after acute stroke. From August 2019 to December 2020, 45 patients with post-stroke dysphagia were selected as research subjects, and randomly divided into 3 groups: the high frequency stimulation on bilateral hemisphere group (High group), bilateral high frequency stimulation on the affected hemisphere and low frequency stimulation on the unaffected hemisphere group (High-low group), and sham stimulation group (Sham group). On the basis of routine swallowing training (30 min) for all patients, the high group received 5 Hz rTMS in both hemispheres, the high- low group received 5 Hz rTMS in the unaffected hemisphere, 1 Hz rTMS in the affected hemisphere, and the sham stimulation group received sham stimulation in bilateral hemisphere. All participants were assessed with dysphagia handicap index (DHI), functional oral intake scale (FOIS) and videofluoroscopic swallowing study (VFSS) before the intervention (T1), immediately after intervention (T2) and 1 month after the intervention (T3). Meanwhile, according to the results of VFSS, Rosenbek penetration aspiration scale (PAS), the moving distance of hyoid bone towards the superior side (H), and pharyngeal response time (T) were analyzed and evaluated. After intervention, all three groups showed significant improvement in post-treatment scores from baseline (P = 0.000). The results of DHI, PAS and H showed that the improvement in high group and high-low group was significantly greater than sham group (P = 0.000). The results of FOIS and T showed that the improvement of bilateral high-frequency group was significantly greater than that of high-low group and sham group (P = 0.000), and the difference lasted until 1 month after the end of treatment. Therefore, bilateral pharyngeal cortex high frequency rTMS and affected side high frequency/unaffected side low frequency rTMS can effectively improve swallowing disorder after acute stroke. However, the effect of bilateral high frequency rTMS is significantly higher than high-low in improving oral feeding function and pharyngeal response time.

The effect of corticosteroid injection in the treatment of greater trochanter pain syndrome: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: corticosteroid injection (CSI) has been used to treat greater trochanter pain syndrome (GTPS) for many years. However, so far, the efficacy of CSI in the treatment of GTPS is still controversial. Therefore, the aim of this review is to evaluate the effectiveness of CSI in comparison with sham intervention, nature history, usual care, platelet-rich plasma (PRP), physiotherapy/exercise therapy, dry needling, or other nonsurgical treatment for improvements in pain and function in GTPS. METHODS: PubMed (Medline), Embase, Cochrane Library were searched from their inception until April 2021. Randomized controlled trails (RCTs) comparing CSI to nonsurgical treatment were included. Data on the effect of CSI on pain and function were extracted and checked by two review authors independently. The treatment effect was analyzed in the short term, medium term, and long term. RESULTS: Eight RCTs (764 patients) were included. This review suggests CSI may be superior to usual care and 'wait and see,' ESWT, but may not be superior to exercise, PRP, dry needling, and sham intervention in short-term pain or function improvement. In terms of medium-term pain or function improvement, CSI may be superior to usual care and 'wait and see,' but may not be superior to PRP. In terms of long-term pain or function improvement, CSI may be inferior to PRP and ESWT, but it may be superior to usual care and 'wait and see' at 12 months. CONCLUSIONS: Due to the small sample size and lack of sufficient clinical studies, current evidence is equivocal regarding the efficacy of CSI in the treatment of GTPS. Considering the limitations, more large-sample and high-quality RCTs are needed to prove the therapeutic effect of CSI on GTPS. TRIAL REGISTRATION: PROSPERO registration number: CRD42021247991. Registered 09 May 2021.

Vagus nerve stimulation alleviated cerebral ischemia and reperfusion injury in rats by inhibiting pyroptosis via α7 nicotinic acetylcholine receptor.

Cumulative evidence suggests that pyroptosis, a new sort of programmed cell death, is closely related to cerebral ischemia/reperfusion (I/R) injury. Our previous studies have testified that vagus nerve stimulation (VNS) was involved in many different neuroprotective and neuroplasticity pathways via α7 nicotinic acetylcholine receptor (α7nAchR), a vital node of the cholinergic anti-inflammatory pathway during cerebral I/R injury. We aimed to determine the neuroprotective effects of VNS through α7nAchR-mediated inhibition of pyroptosis. Focal cerebral ischemic stroke rat models were obtained by middle cerebral artery occlusion for 120 min. Expression of the NLRP3 inflammasome was evaluated using western blotting and immunofluorescence (IF) staining. The neurological deficit score, infarct volume, TUNEL staining findings, transmission electron microscopy findings, and expression of inflammatory cytokines were assessed 3 days after I/R injury. Our findings suggested that the protein expression levels of NLRP3, GSDMD-N, cleaved caspase-1, and ASC gradually increased until they peaked on day 3 after I/R injury. VNS inhibited the expression of pyroptosis-related molecules and decreased the number of pyroptotic cells and membrane pores. Administration of α7nAchR-antagonist and agonist helped in further assessment of the role of α7nAchR in pyroptosis. α7nAchR-agonist mimicked VNS's neuroprotective effects on the improvement of neurological deficits, the reduction of infarct volumes, and the inhibition of neuronal pyroptosis after cerebral I/R injury. Conversely, the neuroprotection provided by VNS could be reversed by the administration of α7nAchR-antagonist. In conclusion, VNS-induced neuroprotection via inhibition of neuronal pyroptosis was α7nAchR-dependent, highlighting the pivotal role of α7nAChR in suppressing cellular pyroptosis and neuroinflammation. These findings may allow a better understanding of treatment principles for cerebral I/R injury.

Efficacy and safety of transcutaneous auricular vagus nerve stimulation combined with conventional rehabilitation training in acute stroke patients: a randomized controlled trial conducted for 1 year involving 60 patients.

Transcutaneous auricular vagus nerve stimulation (ta-VNS) is a novel noninvasive treat-ment for stroke that directly stimulates the peripheral auricular branch of the vagus nerve. There have been recent reports that ta-VNS combined with conventional rehabilitation training promotes the recovery of neurological function of patients with acute stroke. However, these were small-sample-sized studies on the recovery of neurological function in patients after percutaneous vagus nerve stimulation in the subacute and chronic phases after stroke. This double-blinded randomized controlled trial involved 60 acute ischemic or hemorrhagic stroke patients aged 18-80 years who received treatment in the Second Affiliated Hospital of Chongqing Medical University. The subjects were randomly assigned to receive ta-VNS or sham ta-VNS combined with conventional rehabilitation training. The follow-up results over 1 year revealed that ta-VNS combined with conventional rehabilitation training greatly improved the recovery of motor and sensory functions and emotional responses compared with sham ta-VNS combined with conventional rehabilitation training. There were no obvious side effects. These findings suggest that ta-VNS combined with conventional rehabilitation training for the treatment of acute ischemic or hemorrhagic stroke patients is safe and effective.

High Level of the Fibrin Degradation Products at Admission Predicts Parenchymal Hematoma and Unfavorable Outcome of Ischemic Stroke After Intravenous Thrombolysis.

BACKGROUND AND PURPOSE: We aim to investigate whether the higher admission fibrin degradation products (FDPs) levels are associated with parenchymal hematomas (PHs) and unfavorable outcome after intravenous thrombolysis (IVT). METHODS: Consecutive patients with acute ischemic stroke treated with IVT were studied. The FDP level was obtained on admission. PH was evaluated 24 h after treatment. The unfavorable outcome was defined as a 90-day modified Rankin Scale >2. The multivariable linear stepwise regression was used to assess independent factors associated with the log-transformed FDP (lgFDP). The receiver operating characteristics (ROCs) curve analysis was used to determine the predictive value of the FDP level for PH and unfavorable outcome. The logistic regression was used to identify independent predictors for PH and unfavorable outcome. The mediation analyses were performed to investigate associations among the FDP level, PH, and outcome. RESULTS: A total of 181 patients were included in the final analyses [median age, 73 (63-79) years; 102 (56.4%) males; and the median baseline National Institutes of Health Stroke Scale (NIHSS) score, 8 (5-15)]. The lgFDP was independently associated with age (B = 0.011, 95% CI 0.006-0.015, p < 0.001) and the baseline NIHSS score (B = 0.016, 95% CI 0.008-0.025, p < 0.001). The FDP was positively associated with PH [odds ratio (OR) 1.034, 95% CI 1.000-1.069; p = 0.047]. According to the ROC analysis, the best discriminating factor for unfavorable outcome was the FDP ≥3.085 µg/ml. The FDP ≥3.085 µg/ml was an independent predictor of unfavorable outcome (OR 7.086, 95% CI 2.818-17.822; p < 0.001). Mediation analysis revealed that the association of the FDP ≥3.085 µg/ml with unfavorable outcome was not mediated by PH (p = 0.161). CONCLUSION: The admission FDP levels can predict PH and unfavorable outcome in patients with acute ischemic stroke after IVT. PH does not mediate the effect of the FDP level on the outcome.

PPAR-γ Mediates Ta-VNS-Induced Angiogenesis and Subsequent Functional Recovery after Experimental Stroke in Rats.

BACKGROUND: Neoangiogenesis after cerebral ischemia in mammals is insufficient to restore neurological function, illustrating the need to design better strategies for improving outcomes. Our previous study has suggested that transcutaneous auricular vagus nerve stimulation (ta-VNS) induced angiogenesis and improved neurological functions in a rat model of cerebral ischemia/reperfusion (I/R) injury. However, the mechanisms involved need further exploration. Peroxisome proliferator-activated receptor-γ (PPAR-γ), well known as a ligand-modulated nuclear transcription factor, plays a crucial role in the regulation of cerebrovascular structure and function. Hence, the present study was designed to explore the role of PPAR-γ in ta-VNS-mediated angiogenesis and uncover the possible molecular mechanisms against ischemic stroke. METHODS: Adult male Sprague-Dawley rats were transfected with either PPAR-γ small interfering RNA (siRNA) or lentiviral vector without siRNA prior to surgery and subsequently received ta-VNS treatment. The expression and localization of PPAR-γ in the ischemic boundary after ta-VNS treatment were examined. Subsequently, neurological deficit scores, neuronal damage, and infarct volume were all evaluated. Additionally, microvessel density, endothelial cell proliferation condition, and the expression of angiogenesis-related molecules in the peri-infarct cortex were measured. RESULTS: We found that the expression of PPAR-γ in the peri-infarct cortex increased at 14 d and reached normal levels at 28 d after reperfusion. Ta-VNS treatment further upregulated PPAR-γ expression in the ischemic cortex. PPAR-γ was mainly expressed in neurons and astrocytes. Furthermore, ta-VNS-treated I/R rats showed better neurobehavioral recovery, alleviated neuronal injury, reduced infarct volume, and increased angiogenesis, as indicated by the elevated levels of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and phosphorylated endothelial nitric oxide synthase (P-eNOS). Surprisingly, the beneficial effects of ta-VNS were weakened after PPAR-γ silencing. CONCLUSIONS: Our results suggest that PPAR-γ is a potential mediator of ta-VNS-induced angiogenesis and neuroprotection against cerebral I/R injury.

α7nAchR mediates transcutaneous auricular vagus nerve stimulation-induced neuroprotection in a rat model of ischemic stroke by enhancing axonal plasticity.

Axonal plasticity is important for neurofunctional recovery after stroke. This study aimed to explore the role of transcutaneous auricular vagus nerve stimulation (ta-VNS) on axonal plasticity and its underlying association with the α7 nicotinic acetylcholine receptor(α7nAchR) after cerebral ischemia/reperfusion (I/R) injury. Adult male Sprague-Dawley rats were pretreated by intraperitoneal injection with either phosphate-buffered saline (PBS) or an α7nAchR antagonist and then subjected to middle cerebral artery occlusion and ta-VNS treatment. α7nAchR expression and localization in the peri-infarct cortex were examined after ta-VNS treatment. Subsequently, neurologic scores were assessed with a battery of tests. Axonal regeneration, indicated by upregulation of growth-associated protein 43 (GAP-43) and neurofilament protein 200 (NF-200), was assessed. Axonal reorganization was examined on the basis of anterograde movement of the neuronal molecular probe biotin dextran amine. Additionally, brain-derived neurotrophic factor (BDNF)-associated signaling was measured 28d after I/R. Our findings showed that ta-VNS treatment enhanced α7nAchR expression in the ischemic cortex. α7nAchR colocalized with DCX and Nestin after reperfusion. Furthermore, ta-VNS-treated I/R rats displayed enhanced neurobehavioral performance and increased axonal plasticity (axonal regeneration and axonal reorganization), as indicated by elevated levels of BDNF/cyclic AMP (cAMP)/protein kinase A (PKA)/phosphorylated cAMP response element-binding protein pathway (p-CREB) pathway members. Strikingly, the beneficial effects of ta-VNS were diminished after α7nAchR blockade. In conclusion, our study is the first to show that α7nAchR is a potential mediator of ta-VNS-induced neuroprotection in the chronic phase of stroke and that its effects may be related to enhanced axonal plasticity through activation of the BDNF/cAMP/PKA/p-CREB pathway.

Environmental Enrichment Improves Spatial Learning and Memory in Vascular Dementia Rats with Activation of Wnt/ß-Catenin Signal Pathway.

BACKGROUND Environmental enrichment (EE) has a beneficial effect on some neuropsychiatric disorders. In this study, we aimed to investigate whether environmental enrichment could improve the spatial learning and memory in rats with vascular dementia (VaD) and the mechanism underpinning it. MATERIAL AND METHODS Bilateral common carotid occlusion (2-vessel occlusion [2VO]) was used to develop the animal model of vascular dementia. Adult male Sprague-Dawley (SD) rats were used in the experiment and were randomly divided into 4 groups: sham group, 2VO group, sham+EE group, and 2VO+EE group (n=19/group). The 2VO group and 2VO+EE group underwent bilateral common carotid occlusion. Two different housing conditions were used in this experiment: standard environment (SE) and enriched environment (EE). Rats in the sham group and 2VO group were put into SE cages for 4 weeks, while rats in the sham+EE group and 2VO+EE group were put in EE cages for 4 weeks. The Morris water maze and Y-maze were used to assess spatial learning and memory. Apoptosis was detected by TUNEL. The damage of neurons in the hippocampus was assessed by Nissl staining. The level of wnt pathway proteins were detected by Western blot. RESULTS Compared with the 2VO group, the rats in the 2VO+EE group had better behavioral performance, fewer apoptotic neurons, and more surviving neurons. Western blot analysis showed that the levels of wnt pathway proteins were higher in 2VO+EE rats than in the 2VO group. CONCLUSIONS Environmental enrichment can improve the spatial learning and memory in rats with vascular dementia, and the mechanism may be related to activation of the wnt/ß-catenin signal pathway.

Erratum to: Feasibility of focal cerebral ischemia and reperfusion surgery combined with chronic unpredictable mild stress to simulate the post-stroke depressive state in rats.

Erratum to: Behav Brain Funct (2015) 11:39, DOI 10.1186/s12993­015­0085­5. Unfortunately the original version of this article contained an error. After publication it was brought to our attention that one of the authors' names was incorrectly spelt. The original spelling reads as "LiXinhao Jin", however the correct spelling should be Xinhao Jin. This has now been updated on the website.

Feasibility of focal cerebral ischemia and reperfusion surgery combined with chronic unpredictable mild stress to simulate the post-stroke depressive state in rats.

OBJECTIVE: To evaluate the feasibility of focal cerebral ischemia and reperfusion (FCIR) surgery combined chronic unpredictable mild stress (CUMS) to simulate the post-stroke depression (PSD) state in rats. METHODS: Sprague-Dawley male rats were divided randomly into five groups: the normal, sham, FCIR, CUMS, and FCIR + CUMS (F/C) groups. Rats in the FCIR and F/C groups underwent an FCIR operation. Rats in CUMS and F/C groups were single-housed and exposed to CUMS for 4 weeks. Rats in the F/C group underwent CUMS for 4 weeks after FCIR surgery. The gain in bodyweight, the sugar consumption ratio in a sucrose preference test (SPT), and behavior, including spontaneous moves (SM), the duration of time spent in the center arena (duration), and the number of rearings (rearing) in an open field test (OFT), were evaluated. RESULTS: Rats in the CUMS and F/C groups had a smaller gain in bodyweight (P < 0.05). The sugar consumption ratio was reduced significantly in the CUMS and F/C groups compared with the normal and FCIR groups (P < 0.05). The number of SM was significantly lower in the FCIR group compared with the normal group. SM, duration, and rearing were reduced significantly in the CUMS and F/C groups relative to the normal group. Furthermore, the number of rearings was lower in the F/C group compared with the CUMS group. CONCLUSION: Anhedonia, a lack of curiosity, and inactivity were observed in the F/C rats, which exhibited depression-like symptoms after FCIR surgery.

Endovascular versus Non-Interventional Therapy for Cervicocranial Artery Dissection in East Asian and Non-East Asian Patients: a Systematic Review and Meta-analysis.

Endovascular methods have been increasingly applied in treating cervicocranial artery dissection (CCAD). Anti-thrombotic therapy, which is used in non-interventional care of CCAD patients, has differential effects in East Asian patients. Therefore, we aimed to compare the clinical outcomes of endovascular versus non-interventional therapy for CCAD in East Asians and non-East Asians. A search was performed for studies comparing endovascular and non-interventional approaches to CCAD patients. Rates of recovery, disability, and mortality were used to assess these approaches in East Asian and non-East Asian patients. Subgroup analyses were conducted for CCAD patients with ruptured dissections. Eleven East Asian studies and five non-East Asian studies were included. The subgroup analyses for CCAD patients with ruptured dissections on mortality (East Asian odds ratio [OR] [95% confidence interval [CI]]: 0.24 [0.08-0.71], P = 0.01; I(2) = 34%) and good recovery (East Asian OR [95% CI]: 3.79 [1.14-12.60], P = 0.03; I(2) = 54%) revealed that endovascular therapy is significantly superior to non-interventional therapy for East Asians. No differences in treatment effect upon mortality, disability, or good recovery outcomes were found for the CCAD populations-at-large nor for non-East Asian CCAD patients with ruptured dissections. Endovascular therapy appears to be superior to non-interventional therapy for East Asian CCAD patients with ruptured dissections.

Pathological changes on human breast cancer specimens ablated in vitro with high-intensity focused ultrasound.

The purpose of this study was to evaluate the pathologic changes of human breast cancer specimens ablated with high-intensity focused ultrasound (HIFU) in vitro. Twenty specimens of pathologically confirmed breast cancer tissue were ablated with ultrasound-guided HIFU. The evaluation methods include histopathologic observation using hematoxylin-eosin staining, electron microscopic imaging, enzyme histochemical and immunohistochemical examination on tumor antigens. Vacuole-like structures in cytoplasm were observed by histopathologic observation but there were no significant changes in cell morphology and nucleus karyotype. Typical phenomena related to coagulation necrosis were observed in electron microscopic studies; the contour of cell structure was still preserved but the structures of cell (all kinds of organelles and nucleus) were damaged or disappeared. Acid phosphatase and succinate dehydrogenase staining showed that tumor cells were inactivated. In immunohistochemical evaluations, estrogen receptor, progesterone receptor, cerbB-2 and P53 expression changed from 85%, 82%, 75% and 80% in nonablation tissue to no expression in ablated tumor tissue, respectively. We, therefore, conclude that breast cancer cells appear normal contour immediately after ablation with HIFU under light microscopic but they were evaluated to be dead by electron microscopic imaging, enzyme histochemical and immunohistochemical examinations.

db-Cyclic adenosine monophosphate promotes axon regeneration and motor function recovery in cerebral ischemia-reperfusion rats.

BACKGROUND: There is no effective axon regeneration in adult mammalians. OBJECTIVE: To investigate the effects of dual-acid cyclic adenosine monophosphate (db-cAMP) on the axon regeneration, motor function recovery and RhoA signal pathway in cerebral ischemia-reperfusion rats, and to explore the possible clinical application and mechanism. MATERIALS AND METHODS: Middle cerebral artery ischemia-reperfusion model was established by nylon monofilament occlusion method in 105 Sprague-Dawley (SD) rats. Semi-quantitative Western blot analysis was used to assess protein expression level of growth-associated protein-43 (GAP-43) and RhoA. Montoya staircase test score was used to test the motor function of affected forelimb. RESULTS: Compared to the ischemia group, the staircase test score in the db-cAMP group was increased significantly at 30-day (P < 0.05), and GAP-43 protein expression in the db-cAMP group was enhanced significantly at 7-day and 14-day (P < 0.05), and RhoA protein expression in the db-cAMP group was decreased significantly between 24 h to 14-day (P < 0.01). CONCLUSION: These results show that db-cAMP can promote axon regeneration and the recovery of motor function by inhibiting RhoA signal pathway.