Cortical neurogenesis in adult rats after ischemic brain injury: most new neurons fail to mature

The present study examines the hypothesis that endogenous neural progenitor cells isolated from the neocortex of ischemic brain can differentiate into neurons or glial cells and contribute to neural regeneration. We performed middle cerebral artery occlusion to establish a model of cerebral ischemia/reperfusion injury in adult rats. Immunohistochemical staining of the cortex 1, 3, 7, 14 or 28 days after injury revealed that neural progenitor cells double-positive for nestin and sox-2 appeared in the injured cortex 1 and 3 days post-injury, and were also positive for glial ifbrillary acidic protein. New neurons were labeled using bromodeoxyuridine and different stages of maturity were identiifed using doublecortin, microtubule-associated protein 2 and neuronal nuclei antigen immunohistochemistry. Immature new neurons coexpressing doublecortin and bromodeoxyuridine were observed in the cortex at 3 and 7 days post-injury, and semi-mature and mature new neurons double-positive for microtubule-associated protein 2 and bromode-oxyuridine were found at 14 days post-injury. A few mature new neurons coexpressing neuronal nuclei antigen and bromodeoxyuridine were observed in the injured cortex 28 days post-injury. Glial ifbrillary acidic protein/bromodeoxyuridine double-positive astrocytes were also found in the injured cortex. Our ifndings suggest that neural progenitor cells are present in the damaged cortex of adult rats with cerebral ischemic brain injury, and that they differentiate into astrocytes and immature neurons, but most neurons fail to reach the mature stage.

Involvement of nitrergic neurons in colonic motility in a rat model of ulcerative colitis

BACKGROUND The mechanisms underlying gastrointestinal(GI)dysmotility with ulcerative colitis(UC)have not been fully elucidated.The enteric nervous system(ENS)plays an essential role in the GI motility.As a vital neurotransmitter in the ENS,the gas neurotransmitter nitric oxide(NO)may impact the colonic motility.In this study,dextran sulfate sodium(DSS)-induced UC rat model was used for investigating the effects of NO by examining the effects of rate-limiting enzyme nitric oxide synthase(NOS)changes on the colonic motility as well as the role of the ENS in the colonic motility during UC.AIM To reveal the relationship between the effects of NOS expression changes in NOS-containing nitrergic neurons and the colonic motility in a rat UC model.METHODS Male rats(n=8/each group)were randomly divided into a control(CG),a UC group(EG1),a UC+thrombin derived polypeptide 508 trifluoroacetic acid(TP508TFA;an NOS agonist)group(EG2),and a UC+NG-monomethyl-L-arginine monoacetate(L-NMMA;an NOS inhibitor)group(EG3).UC was induced by administering 5.5%DSS in drinking water without any other treatment(EG1),while the EG2 and EG3 were gavaged with TP508 TFA and L-NMMA,respectively.The disease activity index(DAI)and histological assessment were recorded for each group,whereas the changes in the proportion of colonic nitrergic neurons were counted using immunofluorescence histochemical staining,Western blot,and enzyme linked immunosorbent assay,respectively.In addition,the contractile tension changes in the circular and longitudinal muscles of the rat colon were investigated in vitro using an organ bath system.RESULTS The proportion of NOS-positive neurons within the colonic myenteric plexus(MP),the relative expression of NOS,and the NOS concentration in serum and colonic tissues were significantly elevated in EG1,EG2,and EG3 compared with CG rats.In UC rats,stimulation with agonists and inhibitors led to variable degrees of increase or decrease for each indicator in the EG2 and EG3.When the rats in EGs developed UC,the mean contraction tension of the colonic smooth muscle detected in vitro was higher in the EG1,EG2,and EG3 than in the CG group.Compared with the EG1,the contraction amplitude and mean contraction tension of the circular and longitudinal muscles of the colon in the EG2 and EG3 were enhanced and attenuated,respectively.Thus,during UC,regulation of the expression of NOS within the MP improved the intestinal motility,thereby favoring the recovery of intestinal functions.CONCLUSION In UC rats,an increased number of nitrergic neurons in the colonic MP leads to the attenuation of colonic motor function.To intervene NOS activity might modulate the function of nitrergic neurons in the colonic MP and prevent colonic motor dysfunction.These results might provide clues for a novel approach to alleviate diarrhea symptoms of UC patients.

Potentiation of the lateral habenula-ventral tegmental area pathway underlines the susceptibility to depression in mice with chronic pain

Chronic pain often develops severe mood changes such as depression.However,how chronic pain leads to depression remains elusive and the mechanisms determining individuals’responses to depression are largely unexplored.Here we found that depression-like behaviors could only be observed in 67.9%of mice with chronic neuropathic pain,leaving 32.1%of mice with depression resilience.We determined that the spike discharges of the ventral tegmental area(VTA)-projecting lateral habenula(LHb)glutamatergic(Glu)neurons were sequentially increased in sham,resilient and susceptible mice,which consequently inhibited VTA dopaminergic(DA)neurons through a LHbGlu-VTAGABA-VTADA circuit.Furthermore,the LHbGlu-VTADA excitatory inputs were dampened via GABAB receptors in a pre-synaptic manner.Regulation of LHb-VTA pathway largely affected the development of depressive symptoms caused by chronic pain.Our study thus identifies a pivotal role of the LHb-VTA pathway in coupling chronic pain with depression and highlights the activity-dependent contribution of LHbGlu-to-VTADA inhibition in depressive behavioral regulation.

Retrospective Examination of Q Fever Endocarditis： An Underdiagnosed Disease in the Mainland of China

Background： Q fever endocarditis, a chronic illness caused by Coxiella burnetii, can be fatal ifmisdiagnosed or left untreated. Despite a relatively high positive rate of Q fever serology in healthy individuals in the mainland of China, very few cases of Q fever endocarditis have been reported. This study summarized cases of Q fever endocarditis among blood culture negative endocarditis （BCNE） patients and discussed factors attributing to the low diagnostic rate. Methods： We identified confirmed cases of Q fever endocarditis among 637 consecutive patients with infective endocarditis （IE） in the Peking Union Medical College Hospital between 2006 and 2016. The clinical findings for each confirmed case were recorded. BCNE patients were also examined and each BCNE patient＇s Q fever risk factors were identified. The risk factors and presence of Q fever serologic testing between BCNE patients suspected and unsuspected of Q fever were compared using the Chi-squared or Chi-squared with Yates＇ correction for continuity. Results： Among the IE patients examined, there were 147 BCNE patients, of whom only 11 patients （7.5%） were suspected of Q fever and undergone serological testing for C. burnetii. Six out of 11 suspected cases were diagnosed as Q fever endocarditis. For the remaining 136 BCNE patients, none of them was suspected of Q fever nor underwent relevant testing. Risk factors for Q fever endocarditis were comparable between suspected and unsuspected patients, with the most common risk factors being valvulopathy in both groups. However, significantly more patients had consulted the Infectious Diseases Division and undergone comprehensive diagnostic tests in the suspected group than the unsuspected group （100% vs. 63%, P = 0.03）. Conclusions： Q fever endocarditis is a serious yet treatable condition. Lacking awareness of the disease may prevent BCNE patients from being identified, despite having Q fever risk factors. Increasing awareness and guideline adherence are crucial in avoiding misdiagnosing and missed diagnosing of the disease.

Brain Abscess Caused by Bacillus megaterium in an Adult Patient

Bacillus megaterium, a Gram-positive, aerobic, spore-forming, rod-shaped bacterium, has been found in widely diverse habitats and has been widely used as a source of recombinant protein in the industry. With a cell length of up to 4 lain and a diameter of 1.5 μm, B. megaterium belongs to one of the largest known bacteria.

A practical community-based response strategy to interrupt Ebola transmission in sierra Leone, 2014–2015

Background:The Ebola virus disease spread rapidly in West Africa in 2014,leading to the loss of thousands of lives.Community engagement was one of the key strategies to interrupt Ebola transmission,and practical community level measures needed to be explored in the field and tailored to the specific context of communities.Methods:First,community-level education on Ebola virus disease(EVD)prevention was launched for the community’s social mobilizers in six districts in Sierra Leone beginning in November 2014.Then,from January to May of 2015,in three pilot communities,local trained community members were organized to engage in implementation of EVD prevention and transmission interruption measures,by involving them in alert case report,contact tracing,and social mobilization.The epidemiological indicators of transmission interruption in three study communities were evaluated.Results:A total of 6016 community social mobilizers from 185 wards were trained by holding 279 workshops in the six districts,and EVD message reached an estimated 631680 residents.In three pilot communities,72 EVD alert cases were reported,with 70.8%of them detected by trained local community members,and 14 EVD cases were finally identified.Contact tracing detected 64.3%of EVD cases.The median duration of community infectivity for the cases was 1 day.The secondary attack rate was 4.2%,and no third generation of infection was triggered.No health worker was infected,and no unsafe burial and noncompliance to EVD control measures were recorded.The community-based measures were modeled to reduce 77 EVD cases,and the EVD-free goal was achieved four months earlier in study communities than whole country of Sierra Leone.Conclusions: The community-based strategy of social mobilization and community engagement was effective in casedetection and reducing the extent of Ebola transmission in a country with weak health system. The successfullypractical experience to reduce the risk of Ebola transmission in the community with poor resources would potentiallybe helpful for the global community to fight against the EVD and the other diseases in the future.