Saikosaponin A improved depression-like behavior and inhibited hippocampal neuronal apoptosis after cerebral ischemia through p-CREB/BDNF pathway.

Post-stroke depression(PSD) is a common complication and associates with poor physical recovery, low quality of life and high mortality after cerebral infarction. However, the pathogenesis of PSD have not been elucidated thoroughly now, and there is a lack of effective therapy in clinic. It reported that Saikosaponin A, one of the main constituents from Chinese herb Bupleurum chinense, has pharmacological activity in anti-depression. Thus, this study aimed to elucidate the potential effects and mechanisms of Saikosaponin A on the depression-like behavior after cerebral ischemic injury in rats. The rat model of PSD was induced by middle cerebral artery occlusion(MCAO) combined with chronic unpredictable mild stress(CUMS) and isolation. Behavior tests including open field test, beam-walking test, sucrose preference and forced swimming tests were performed. Western blot and immunohistochemistry were adopted to evaluate expression of phosphorylated cAMP response element binding protein(p-CREB), brain derived neurotrophic factor(BDNF) and apoptosis-related molecules in the dentate gyrus region of rat hippocampus. The TUNEL assay was used to determine neuronal apoptosis. We found that the rats subjected to MCAO combined with CUMS and isolation experienced significant depressive-like behavior. Administration of Saikosaponin A significantly ameliorated depressive-like behavior, and inhibited neuronal apoptosis, enhanced the level of p-CREB, BDNF and Bcl-2, reduced the level of Bax, Caspase-3 in the hippocampus of PSD rats. These results revealed that Saikosaponin A improved depression-like behavior and inhibited hippocampal neuronal apoptosis after cerebral ischemia, presumably through increasing the expression of BDNF, p-CREB and Bcl-2, as well as decreasing the level of Bax, Caspase-3.

Antidepressant-like effects of paeoniflorin on post-stroke depression in a rat model.

BACKGROUND: Post-stroke depression (PSD) is one of the most prevalent emotional disorders after stroke and often results in poor outcomes. However, the underlying physiopathologic mechanism and effective treatment of PSD remain poorly elucidated. OBJECTIVE: To investigate whether paeoniflorin has antidepressant-like activity in a rat model of PSD. METHODS: Rats were randomly divided into four groups: sham-operated control (Sham), PSD, paeoniflorin (with PSD) and fluoxetine group(with PSD). PSD was developed by the right middle cerebral artery occlusion followed 21 days chronic unpredictable mild stress combined (CUMS) with raised alone. Tests of sucrose preference and open field were used to assess the depression-like behavior. Neurological function was evaluated by neurological deficit score and beam balance test. Expression of phosphorylated CREB (p-CREB) and brain-derived neurotrophic factor (BDNF) in the CA1 region of the hippocampal complex was evaluated by western blot and immunofluorescence. RESULTS: Te depressive-like behaviors markedly improved after paeoniflorin and fluoxetine treatment. Furthermore, paeoniflorin treatment significantly increased BDNF and p-CREB expression in the CA1 region. CONCLUSIONS: Observed results suggested that paeoniflorin could ameliorate the symptoms and improve the functional capability of PSD rats, similar to the effect of fluoxetine. ABBREVIATIONS: PSD: post-stroke depression; CUMS: chronic unpredictable mild stress stimulation; MCAO: middle cerebral artery occlusion; OFT: open field test; SPT: sucrose preference test, NDS: neurological deficit score, BBT: beam balance test; BDNF: brain-derived neurotrophic factor protein; p-CREB: phosphorylated Cyclic-AMP responsive element binding protein.

Fastigial nucleus electrostimulation promotes axonal regeneration after experimental stroke via cAMP/PKA pathway.

Axon regeneration after cerebral ischemia in mammals is inadequate to restore function, illustrating the need to design better strategies for improving outcomes. Improvement of axon regeneration has been achieved through fastigial nucleus electrostimulation (FNS) in animal researches. However, the mechanisms underlying this neuroprotection remain poorly understood. Increasing the levels of the second messenger cyclic AMP (cAMP) enhances axon regeneration, making it an excellent candidate molecule that has therapeutic potential. In the present study, we examined the expression of cAMP signaling in ischemic brain tissues following focal cerebral ischemia. Adult rats were subjected to ischemia induced by middle cerebral artery occlusion (MCAO). A dipolar electrode was placed into the cerebellum to stimulate the cerebellar fastigial nucleus for 1 h after ischemia. Neurological deficits and the expressions of cAMP, PKA (protein kinase A) and ROCK (Rho-kinase) were determined. Axonal regeneration was measured by upregulation of growth-associated protein 43 (GAP43). The data indicated that FNS significantly enhanced axonal regeneration and motor function recovery after cerebral ischemia. FNS also significantly increased cAMP and PKA levels after ischemic brain injury. All the beneficial effects of FNS were blocked by Rp-cAMP, an antagonist of PKA. Our research suggested that the axonal regeneration conferred by FNS was likely achieved via the regulation of cAMP/PKA pathway.

Epidemiology of esophageal cancer in Yanting - regional report of a national screening programme in China.

BACKGROUND AND OBJECTIVES: Yanting in Sichuan Province is one of the highest risk areas of esophageal cancer (EC) in the world. We here summarize the epidemiology of EC in Yanting using data from the national screening programme during 2006-2011. METHODS: Random cluster sampling was used to select a proportion of natural villages from six towns in Yanting, and residents aged 40-69 years old were invited for screening. Participants were screened using endoscopy with iodine staining and then confirmed by histological examinations. RESULTS: The overall detection rates of low-grade hyperplasia (LH), moderate hyperplasia (MH), high-grade hyperplasia (HH), carcinoma in situ (CIS), intramucosal carcinoma (IC) and invasive carcinoma (INC) were 5.33%, 1.28%, 0.68% , 0.15% , 0.06% and 0.29%, respectively. The detection rates of LH, MH, HH and INC increased with age, reaching the peak among those aged 60-65 years, and the prevalences of LH and MH were higher among men than among women. In addition, the detection rates of hyperplasia were much higher in mountainous than in hilly areas. CONCLUSIONS: Among the high risk population, there are a great number of people with early-stage EC or precancerous conditions who do not have presenting symptoms. In particular, the elderly, men, or those living in mountainous areas are the most vulnerable population. It is therefore important to reinforce health education and screening services among such high risk populations.

[Results of a screening program on high incidence area of esophageal cancer in Yanting Sichuan from 2006 to 2011].

OBJECTIVE: To study the prevalence of esophageal cancer and various lesions of esophagus in high risk areas through a screening program for early diagnosis and treatment. METHODS: Random cluster sampling method was used to select some portions of a natural village as screening object in the high risk areas of esophageal cancer, from 2006 to 2011. Endoscope iodine staining and index biopsy screening methods were used on people with high risk and followed by pathological exams for confirmation. RESULTS: The detection rates regarding mild esophageal hyperplasia, moderate and severe esophageal hyperplasia were 5.33% (803/15 065), 1.28% (193/15 065), 0.68% (102/15 065) respectively while the detection rates on carcinoma in situ, intramucosal carcinoma and invasive cancer were 0.15% (22/15 065), 0.06% (9/15 065), 0.29% (43/15 065) respectively. The detection rate in male esophageal hyperplasia was higher than in female. People younger than 65 years old, the detection rates on mild, moderate or severe esophageal hyperplasia and invasive cancer showed an increase with age, with the 60-year-olds group reaching the highest. The detection rates on the above said diseases were 7.72% (198/2565), 2.07% (53/2565), 1.29% (33/2565), 0.51% (13/2565) respectively. The detection rates on mild, moderate or severe esophageal hyperplasia varied in different years and with statistically significant differences (P < 0.001) but did not show any obvious trend of changing. Geographical distribution of mild esophageal hyperplasia, moderate esophageal hyperplasia, severe esophageal hyperplasia also significantly varied in different villages (P < 0.001). The highest detection rate in the mountainous villages was seen the highest while the detection rate of village from hilly areas was the lowest. CONCLUSION: There were considerable numbers of patients with precancerous lesions in the general population from the high risk areas. The detection rate of esophageal cancer in the mountain residents was higher than the rate in the hilly areas. Men and the elderly were the key populations calling for esophageal cancer prevention programs to be carried out.