Background Chronic cerebral hypoperfusion (CCH) underlies secondary brain injury following certain metabolic disorders and central nervous system (CNS) diseases. Dysregulation of the microbiota-gut-brain axis can exacerbate various CNS disorders through aberrantly expressed metabolites such as short-chain fatty acids (SCFAs). Yet, its relationship with CCH remains to be demonstrated. And if so, it is of interest to explore whether restoring gut microbiota to maintain SCFA metabolism could protect against CCH. Results Rats subjected to bilateral common carotid artery occlusion (BCCAO) as a model of CCH exhibited cognitive impairment, depressive-like behaviors, decreased gut motility, and compromised gut barrier functions. The 16S ribosomal RNA gene sequencing revealed an abnormal gut microbiota profile and decreased relative abundance of some representative SCFA producers, with the decreased hippocampal SCFAs as the further evidence. Using fecal microbiota transplantation (FMT), rats recolonized with a balanced gut microbiome acquired a higher level of hippocampal SCFAs, as well as decreased neuroinflammation when exposed to lipopolysaccharide. Healthy FMT promoted gut motility and gut barrier functions, and improved cognitive decline and depressive-like behaviors by inhibiting hippocampal neuronal apoptosis in BCCAO rats. Long-term SCFA supplementation further confirmed its neuroprotective effect in terms of relieving inflammatory response and hippocampal neuronal apoptosis following BCCAO. Conclusion Our results demonstrate that modulating the gut microbiome via FMT can ameliorate BCCAO-induced gut dysbiosis, cognitive decline, and depressive-like behaviors, possibly by enhancing the relative abundance of SCFA-producing floras and subsequently increasing SCFA levels.

Background Jingshu Keli (or Jingshu granules), a traditional Chinese medicine, are widely used for treating cervical spondylotic radiculopathy in China; however, no randomized, double-blind, controlled study has verified their effectiveness. Purpose To evaluate the efficacy and safety of Jingshu Keli for the treatment of cervical spondylotic radiculopathy in a randomized controlled trial. Design From August 2015 to July 2017, a multicenter, randomized, double-blind, placebo-controlled trial was conducted at 13 large- and medium-sized hospitals in China. Patient sample A total of 360 and 120 patients were initially enrolled in the Jingshu and control groups, respectively; 386 patients completed the study, with 299 in the Jingshu group and 87 in the control group. Outcome measures The main index for evaluating the curative effect was the pain score on a visual analogue scale (VAS; 0–100 points). Methods All patients were administered a bag of Jingshu Keli or placebo 3 times a day for 4 weeks, and were interviewed at the second and fourth weeks. The decrease in pain scores and rate of change in pain scores after treatment were calculated, related laboratory indices were reviewed, and adverse reactions were recorded. Results In the Per Protocol Set (PPS) analysis, the baseline pain VAS scores in the control and Jingshu groups were 49.31 ​± ​6.97 and 50.06 ​± ​7.33, respectively, with no significant difference between the groups (P ​> ​0.05). While there were no differences at 2 weeks between groups, at four weeks the pain VAS scores in the control and Jingshu groups decreased by 12.86 ​± ​13.45 and 22.72 ​± ​15.08, respectively relative to the values at baseline, with significant group differences (P ​< ​0.0001). While there were similar significant differences between the groups (P ​< ​0.0001) in the Full Analysis Set (FAS) analyses neither group achieved the minimal clinically important difference at any time point. Conclusions Jingshu Keli are effective for the treatment of cervical spondylotic radiculopathy. Translational potential statement This is the first prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial that confirmed the clinical efficacy and safety of Jingshu Keli for treating cervical spondylotic radiculopathy, which can provide evidence for clinical treatment.

To observe the changes of Nogo/NgR and Rho/ROCK signaling pathway-related gene and protein expression in rats with spinal cord injury (SCI) treated with electroacupuncture (EA) and to further investigate the possible mechanism of EA for treating SCI. Methods: Allen's method was used to create the SCI rat model. Sixty-four model rats were further subdivided into four subgroups, namely, the SCI model group (SCI), EA treatment group (EA), blocking agent Y27632 treatment group (Y27632) and EA+blocking agent Y27632 treatment group (EA+Y), according to the treatment received. The rats were subjected to EA and/or blocking agent Y27632 treatment. After 14 days, injured spinal cord tissue was extracted for analysis. The mRNA and protein expression levels were determined by real-time fluorescence quantitative PCR and Western blotting, respectively. Cell apoptosis changes in the spinal cord were evaluated by in situ hybridization. Hindlimb motor function in the rats was evaluated by Basso-Beattie-Bresnahan assessment methods. Results: Except for RhoA protein expression, compared with the SCI model group, EA, blocking agent Y27632 and EA+blocking agent Y27632 treatment groups had significantly reduced mRNA and protein expression of Nogo-A, NgR, LINGO-1, RhoA and ROCK II in spinal cord tissues, increased mRNA and protein expression of MLCP, decreased p-MYPT1 protein expression and p-MYPT1/MYPT1 ratio, and caspase3 expression, and improved lower limb movement function after treatment for 14 days (P<0.01 or <0.05). The combination of EA and the blocking agent Y27632 was superior to EA or blocking agent Y27632 treatment alone (P < 0.01 or <0.05). Conclusion: EA may have an obvious inhibitory effect on the Nogo/NgR and Rho/ROCK signaling pathway after SCI, thereby reducing the inhibition of axonal growth, which may be a key mechanism of EA treatment for SCI.

Microvascular imaging based on indocyanine green is an important tool for surgeons who carry out extracranial–intracranial arterial bypass surgery. In terms of blood perfusion, indocyanine green images contain abundant information, which cannot be effectively interpreted by humans or currently available commercial software. In this paper, an automatic processing framework for perfusion assessments based on indocyanine green videos is proposed and consists of three stages, namely, vessel segmentation based on the UNet deep neural network, preoperative and postoperative image registrations based on scale-invariant transform features, and blood flow evaluation based on the Horn–Schunck optical flow method. This automatic processing flow can reveal the blood flow direction and intensity curve of any vessel, as well as the blood perfusion changes before and after an operation. Commercial software embedded in a microscope is used as a reference to evaluate the effectiveness of the algorithm in this study. A total of 120 patients from multiple centers were sampled for the study. For blood vessel segmentation, a Dice coefficient of 0.80 and a Jaccard coefficient of 0.73 were obtained. For image registration, the success rate was 81%. In preoperative and postoperative video processing, the coincidence rates between the automatic processing method and commercial software were 89 and 87%, respectively. The proposed framework not only achieves blood perfusion analysis similar to that of commercial software but also automatically detects and matches blood vessels before and after an operation, thus quantifying the flow direction and enabling surgeons to intuitively evaluate the perfusion changes caused by bypass surgery.