Comprehensive exercise reduces traumatic brain injury deficits via improving the neural network function of hippocampal CA1 and medial entorhinal cortex.

The present study aimed to investigate the alterations in functional interaction between hippocampal CA1 and medial entorhinal cortex (MEC) after moderate traumatic brain injury (TBI) in C57BL/6J mice, and the possible beneficial effects of comprehensive exercise (CE). Following TBI, two microelectrodes were implanted into CA1 and MEC for extracellular recording. We found a clear synchronization of neuronal firing in CA1 and MEC, particularly within 100 Hz and peaked at 20-30 Hz range. TBI induced a significant reduction (P < 0.001) of the coherences of firing between 20-40 Hz frequency band. The mean power spectral densities (PSD) of all group mice in MEC were steadily larger than the values in CA1 in both 20-40 Hz and 56-100 Hz ranges. TBI induced significant and consistent increases of averaged 20-40 Hz or 56-100 Hz PSD (P < 0.001 or P < 0.01) in both CA1 and MEC. Injured mice displayed more varied firing patterns, and showed increased burst frequency (BF), burst duration (BD), inter-spike intervals (ISI) and inter-burst interval (IBI). Injured mice also showed worsened neurological function, sleep, gait performance, and working memory. CE facilitated the restoration of aforementioned electrophysiological characteristics and functional deficits in TBI mice. These results suggest that the beneficial effects of CE on TBI functional deficits may be partly attributed to improved neuronal network interaction between CA1 and MEC.

Modified mouse model of repeated mild traumatic brain injury through a thinned-skull window and fluid percussion.

Mild traumatic brain injury (mTBI) is a clinically highly heterogeneous neurological disorder, none of the existing animal models can replicate the entire sequelae. This study aimed to develop a modified closed head injury (CHI) model of repeated mTBI (rmTBI) for investigating Ca2+ fluctuations of the affected neural network, the alternations of electrophysiology, and behavioral dysfunctions. The transcranial Ca2+ study protocol includes AAV-GCaMP6s infection in the right motor cortex, thinned-skull preparation, and two-photon laser scanning microscopy (TPLSM) imaging. The CHI rmTBI model is fabricated using the thinned-skull site and applying 2.0 atm fluid percussion with 48-h interval. The neurological dysfunction, minor motor performance, evident mood, spatial working, and reference deficits we found in this study mimic the clinically relevant syndromes after mTBI. Besides, our study revealed that there was a trend of transition from Ca2+ singlepeak to multipeak and plateau, and the total Ca2+ activities of multipeaks and plateaus (p < .001 vs. pre-rmTBI value) were significantly increased in ipsilateral layer 2/3 motor neurons after rm TBI. In parallel, there is a low-frequency power shift from delta to theta band (p < .01 vs. control) in the ipsilateral layer 2/3 of motor cortex of the rmTBI mice, and the overall firing rates significantly increased (p < .01 vs. control). Moreover, rmTBI causes slight cortical and hippocampal neuron damage and possibly induces neurogenesis in the dentate gyrus (DG). The alternations of Ca2+ and electrophysiological characteristics in layer 2/3 neuronal network, histopathological changes, and possible neurogenesis may play concertedly and partially contribute to the functional outcome post-rmTBI.

Neuroprotective effects of voluntary exercise and Yisaipu after traumatic brain injury in mice.

The mechanisms underlying exercise-induced neuroprotective effects after traumatic brain injury (TBI) remained elusive, and there is a lack of effective treatments for TBI. In this study, we investigated the effects of an integrative approach of exercise and Yisaipu (TNFR-IgG fusion protein, TNF inhibitor) in a mouse TBI model. Male C57BL/6J mice were randomly assigned to a sedentary group or a group that followed a voluntary exercise regimen. The effects of 6-week prophylactic preconditioning exercise (PE) alone or in combination with post-TBI Yisaipu treatment on moderate TBI associated deficits were examined. The results showed that combined treatments of PE and post-TBI Yisaipu were superior to single treatments on reducing sensorimotor and gait dysfunctions in mice. These functional improvements were accompanied by reduced systemic inflammation largely via decreased serum TNF-α, boosted autophagic flux, and mitigated lesion volume after TBI. Given these neuroprotective effects, composite approaches such as a combination of exercise and TNF inhibitor may be a promising strategy for facilitating functional recovery from TBI and are worth further investigation.

Pathophysiology of stress granules: An emerging link to diseases (Review).

Under unfavorable environmental conditions, eukaryotic cells may form stress granules (SGs) in the cytosol to protect against injury and promote cell survival. The initiation, mRNA and protein composition, distribution and degradation of SGs are subject to multiple intracellular post­translational modifications and signaling pathways to cope with stress damage. Despite accumulated comprehensive knowledge of their composition and dynamics, the function of SGs remains poorly understood. When the stress persists, aberrant and/or persistent intracellular SGs and aggregation of SGs­related proteins may lead to various diseases. In the present article, the research progress regarding the generation, modification and function of SGs was reviewed. The regulatory effects and influencing factors of SGs in the development of tumors, cardiovascular diseases, viral infections and neurodegenerative diseases were also summarized, which may provide novel insight for preventing and treating SG­related diseases.

A convenient synthesis of N-aryl benzamides by rhodium-catalyzed ortho-amidation and decarboxylation of benzoic acids.

The rhodium-catalyzed amidation of substituted benzoic acids with isocyanates by directed CH functionalization followed by decarboxylation to afford the corresponding N-aryl benzamides is demonstrated, in which the carboxylate serves as a unique, removable directing group. Notably, less common meta-substituted N-aryl benzamides are generated readily from more accessible para- or ortho-substituted groups by employing this strategy.

What should the government do regarding health policy-making to develop community health care in Shanghai?

BACKGROUND: The traditional three-stratum healthcare system, within which municipal, district and community hospitals all paid great attention to improving medical treatment service by developing medical technology, is no longer able to meet the current health needs in Shanghai. In 1997, the Chinese government called for the development of community health services to serve as a basic platform to provide public health service and basic medical cure. However, because the market-oriented economic reform was based on a fee-for-service mechanism (without a strict monitoring system), most community health centers (CHCs) still put great effort into developing medical services geared to profit, rather than to provide proper medical service for all and a "quality" public health service. To try to solve the problem, some government-controlled payment (GCP) system has been implemented in CHCs gradually in districts of Shanghai. The study intended to evaluate the impact of GCP solutions already implemented, as well as the impact of the standardized GCP system with supplementary solutions, in enabling CHCs to focus on providing quality public health services and appropriate medical treatment, rather than focusing on profit and loss, in order to meet the health needs aroused by major socioeconomic transition in Shanghai. METHOD: In order to make a systematic assessment, a standardized form of GCP was piloted for 6 months in Changning, Zhabei, and Songjiang districts, representing rich urban, poor urban and rich rural districts, respectively. We employed an evaluation index system with 26 indicators, based on a systematic review of literature and two rounds of Delphi consultation. The evaluation index system investigates four main themes of the reform: the government's role, the reform measures, the performance of CHC services and satisfaction with CHC services. We conducted an evaluation of the impact of both various types of GCP implemented in recent years and the standardized GCP system used during the more recent pilot project conducted across districts with different socioeconomic profiles. Cross-sectional comparisons between the pilot districts and control districts with similar socioeconomic context were also carried out to observe further the impact of the GCP system. RESULT: Various GCP systems were implemented in 2006 in Changning and Songjiang district and in 2007 in Zhabei district. These GCP systems were standardized in April 2009 and piloted for 6 months on this new basis in these three districts (Changning, Songjiang and Zhabei). The overall "outcome" scores based on an evaluation index applied to Changning, Zhabei, and Songjiang districts have been generally improving from 2004 to 2009. The improvements in outcome were significant after the districts had implemented various GCP solutions and increased further, albeit to a lesser extent, in the three pilot districts from April 2009 to September 2009, when the GCP systems were standardized by the implementation of some supplementary solutions. Cross-sectional comparisons between the pilot districts and control districts also indicated that CHC performance was consistently better in the pilot districts after the pilot period than in that of some other "control" districts. CONCLUSION: Although there have been other policies interacting with the impact of GCP, GCP reforms implemented in the pilot districts at different times (as well as the later, standardized GCP system) have been effective in enabling CHCs to focus on providing quality public health services and appropriate medical treatment, rather than concentrating upon profit and loss. The impact of the standardized GCP system was further confirmed by cross-sectional comparisons of some broad indicators, in terms of medical cost, quality of medical service, and coverage of public health service, between the pilot districts and control districts. However, uncertainties exit when looking at individual indicators. Some indicators (see pp. 11-13 and Table 5), such as the service contracting rate with CHCs and the proportion of residents with health records set up, were not sufficient to allow for reasonable estimation of the impact of the GCP. In part this was due to inconsistent data collections. Some indicators, on the other hand, such as the standard management rate of residents with hypertension, were usually affected by the changing government's role over the period. Meanwhile, variations among the three pilot districts with different socioeconomic profiles were observed by several individual indicators within the evaluation index. Further research is needed to investigate the impact of other solutions--such as user fee removal and "zero margin profit" of medicine in CHCs--in order to coordinate other policies with the GCP to improve CHCs more effectively. Longer term observation of impact of the standardized GCP system, as well as other influencing factors in Shanghai based on quality data collected on a standard basis, may help improve policy. Moreover, variations in residents' expectations of barriers in access to CHC services and in healthcare-seeking behavior need to be taken into consideration when designing GCP systems for areas with different socioeconomic profiles in order to meet the different health needs which are a consequence of the major socioeconomic changes in Shanghai (and China in general, it could be agreed).