Transplanted neural stem cells modulate regulatory T, γδ T cells and corresponding cytokines after intracerebral hemorrhage in rats.

The immune system, particularly T lymphocytes and cytokines, has been implicated in the progression of brain injury after intracerebral hemorrhage (ICH). Although studies have shown that transplanted neural stem cells (NSCs) protect the central nervous system (CNS) from inflammatory damage, their effects on subpopulations of T lymphocytes and their corresponding cytokines are largely unexplored. Here, rats were subjected to ICH and NSCs were intracerebrally injected at 3 h after ICH. The profiles of subpopulations of T cells in the brain and peripheral blood were analyzed by flow cytometry. We found that regulatory T (Treg) cells in the brain and peripheral blood were increased, but γδT cells (gamma delta T cells) were decreased, along with increased anti-inflammatory cytokines (IL-4, IL-10 and TGF-ß) and decreased pro-inflammatory cytokines (IL-6, and IFN-γ), compared to the vehicle-treated control. Our data suggest that transplanted NSCs protect brain injury after ICH via modulation of Treg and γδT cell infiltration and anti- and pro-inflammatory cytokine release.

Timing and dose regimens of marrow mesenchymal stem cell transplantation affect the outcomes and neuroinflammatory response after ischemic stroke.

AIMS: Intravenous transplantation of bone marrow mesenchymal stem cells (BMSCs) had been documented to improve functional outcome after ischemic stroke. However, the timing and appropriate cell number of transplantation to achieve better outcome after an episode of stroke remain further to be optimized. METHODS: To determine the optimal conditions, we transplanted different concentrations of BMSCs at different time points in a rat model of ischemic stroke. Infarction volume and neurological behavioral tests were performed after ischemia. RESULTS: We found that transplantation of BMSCs at 3 and 24 h, but not 7 days after focal ischemia, significantly reduced the lesion volume and improved motor deficits. We also found that transplanted cells at 1 × 10(6) to 10(7) , but not at 1 × 10(4) to 10(5) , significantly improved functional outcome after stroke. In addition to inhibiting macrophages/microglia activation in the ischemic brain, BMSC transplantation profoundly reduced infiltration of gamma delta T (γδT) cells, which are detrimental to the ischemic brain, and significantly increased regulatory T cells (Tregs), along with altered Treg-associated cytokines in the ischemic brain. CONCLUSIONS: Our data suggest that timing and cell dose of transplantation determine the therapeutic effects after focal ischemia by modulating poststroke neuroinflammation.

Overexpression of adiponectin improves neurobehavioral outcomes after focal cerebral ischemia in aged mice.

AIMS: To study whether adiponectin (APN) could improve neurological outcomes in aged mice after ischemic stroke. METHODS: Adeno-associated virus carrying APN gene was injected into aged and young adult mice 7 days before transient middle cerebral artery occlusion (tMCAO). Atrophic volumes and neurobehavioral deficiencies were determined up to 28 days after tMCAO. Focal angiogenesis was determined based on blood vessel number in the ischemic regions. RESULTS: Increased atrophic volume and more sever neurobehavioral deficits were found in the aged mice compared with young adult mice (P < 0.05). AAV-APN gene transfer attenuated atrophic volume and improved neurobehavioral outcomes, along with increased focal angiogenesis in both aged and young adult mice, compared with control animals (P < 0.05). In addition, the attenuation of atrophic volume and the improvement in neurobehavioral outcomes were much more significant in aged mice than in young adult mice after AAV-APN administration (P < 0.05). The number of microvessels in aged AAV-APN mouse ischemic brain was higher than in young adult AAV-APN treated mouse brain (P < 0.05). CONCLUSIONS: Our results demonstrate that APN overexpression reduces ischemic brain injury and improves neurobehavioral function recovery in aged mice than in young mice, suggesting APN is more beneficial in aged animals after ischemic stroke.

Relationship between symptom response and esophageal pH level on standard dose of esomeprazole treatment for gastroesophageal reflux disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The relationship between symptom elimination and normalization of esophageal acid level of gastroesophageal reflux disease (GERD) on proton-pump inhibitor (PPI) therapy has been questioned. This study aimed to evaluate the relationship between symptom response and gastro-esophageal acidity control in Chinese patients with GERD on esomeprazole therapy, and to assess the role of 24-hour esophageal pH-metry after therapy in GERD patients.</p><p><b>METHODS</b>GERD patients with typical reflux symptoms were enrolled and received esomeprazole 40 mg once daily for 4 weeks. Patients with positive baseline 24-hour esophageal pH-metry were divided into two groups depending on an additional dual-channel 24-hour pH-metry after treatment. The pH- group achieved normalization of esophageal pH level whereas the pH+ group did not.</p><p><b>RESULTS</b>Of the 80 patients studied, 76 had abnormal baseline esophageal pH levels. Of these, 90% (52/58) of symptom-free patients and 67% (12/18) of symptom-persistent patients achieved esophageal pH normalization after therapy (P = 0.030). The mean post-therapy gastric nocturnal percent time of pH < 4.0 was significantly higher in pH+ group than that in pH- group (P < 0.001) after therapy. The multivariate regression analysis identified hiatus hernia (P < 0.001) and persistent reflux symptom (P = 0.004) were two independent factors predicting the low post-therapy esophageal pH level.</p><p><b>CONCLUSIONS</b>Symptom elimination is not always accompanied by esophageal pH normalization, and vice verse. Esophageal pH-metry is recommended for GERD patients with hiatus hernia or with persistent reflux symptoms after PPI therapy.</p>

Impact of risk factors on the severity of esophageal mucosal injury in patients with gastroesophageal reflux disease / 中华消化内镜杂志

Objective To assess the risk factors that could influence the severity of esophageal inju- ry in patients with gastroesophageal reflux disease(GERD).Methods GERD patients diagnosed on the ba- sis of endoscopic reflux esophagitis or pathological results of 24 hour esophageal pH monitoring were divided into three groups as non-erosive reflux disease group(NERD)(n=83),mild esophagitis group(n=51) and severe esophagitis group(n=22).The clinic data and esophageal pH parameters were recorded in the three groups.A logistic regression was used to assess the joint influences of clinic characteristics,hiatus her- nia,and esophageal pH parameters on the severity of esophageal injury.Results Patients in severe esoph- agitis group were more likely to have advanced age and hiatus hernia.The number of supine long reflux epi- sodes measured by esophageal pH monitoring significantly increased with increasing grades of mueosal dam- age(P