Previous studies have shown that vagus nerve stimulation can improve the prognosis of trau-matic brain injury. The aim of this study was to elucidate the mechanism of the neuroprotective effects of vagus nerve stimulation in rabbits with brain explosive injury. Rabbits with brain ex-plosive injury received continuous stimulation (10 V, 5 Hz, 5 ms, 20 minutes) of the right cervical vagus nerve. Tumor necrosis factor-α, interleukin-1βand interleukin-10 concentrations were detected in serum and brain tissues, and water content in brain tissues was measured. Results showed that vagus nerve stimulation could reduce the degree of brain edema, decrease tumor necrosis factor-αand interleukin-1βconcentrations, and increase interleukin-10 concentration after brain explosive injury in rabbits. These data suggest that vagus nerve stimulation may exert neuroprotective effects against explosive injury via regulating the expression of tumor necrosis factor-α, interleukin-1βand interleukin-10 in the serum and brain tissue.

The present study aims to evaluate the effect of bone marrow mesenchymal stem cells on cold stress induced neuronal changes in hippocampal CA1 region of Wistar rats. Bone marrow mes-enchymal stem cells were isolated from a 6-week-old Wistar rat. Bone marrow from adult femora and tibia was collected and mesenchymal stem cells were cultured in minimal essential medium containing 10% heat-inactivated fetal bovine serum and were sub-cultured. Passage 3 cells were analyzed by lfow cytometry for positive expression of CD44 and CD90 and negative expression of CD45. Once CD44 and CD90 positive expression was achieved, the cells were cultured again to 90% conlfuence for later experiments. Twenty-four rats aged 8 weeks old were randomly and evenly divided into normal control, cold water swim stress (cold stress), cold stress + PBS (intra-venous infusion), and cold stress + bone marrow mesenchymal stem cells (1 × 106; intravenous infusion) groups. The total period of study was 60 days which included 1 month stress period followed by 1 month treatment. Behavioral functional test was performed during the entire study period. After treatment, rats were sacriifced for histological studies. Treatment with bone marrow mesenchymal stem cells signiifcantly increased the number of neuronal cells in hippocampal CA1 region. Adult bone marrow mesenchymal stem cells injected by intravenous administration show potential therapeutic effects in cognitive decline associated with stress-related lesions.

This study established an aged rat model of cognitive dysfunction using anesthesia with 2%iso-lfurane and 80%oxygen for 2 hours. Twenty-four hours later, Y-maze test results showed that isoflurane significantly impaired cognitive function in aged rats. Gas chromatography-mass spectrometry results showed that isolfurane also signiifcantly increased the levels of N,N-diethy-lacetamide, n-ethylacetamide, aspartic acid, malic acid and arabinonic acid in the hippocampus of isolfurane-treated rats. Moreover, aspartic acid, N,N-diethylacetamide, n-ethylacetamide and malic acid concentration was positively correlated with the degree of cognitive dysfunction in the isolfurane-treated rats. It is evident that hippocampal metabolite changes are involved in the formation of cognitive dysfunction after isoflurane anesthesia. To further verify these results, this study cultured hippocampal neurons in vitro, which were then treated with aspartic acid (100 μmol/L). Results suggested that aspartic acid concentration in the hippocampus may be a biomarker for predicting the occurrence and disease progress of cognitive dysfunction.

Claudin 14 has been shown to promote nerve repair and regeneration in the early stages of Wallerian degeneration (0–4 days) in rats with sciatic nerve injury, but the mechanism under-lying this process remains poorly understood. This study reported the effects of claudin 14 on nerve degeneration and regeneration during early Wallerian degeneration. Claudin 14 expression was up-regulated in sciatic nerve 4 days after Wallerian degeneration. The altered expression of claudin 14 in Schwann cells resulted in expression changes of cytokines in vitro. Expression of claudin 14 affected c-Jun, but not Akt and ERK1/2 pathways. Further studies revealed that enhanced expression of claudin 14 could promote Schwann cell proliferation and migration. Silencing of claudin 14 expression resulted in Schwann cell apoptosis and reduction in Schwann cell proliferation. Our data revealed the role of claudin 14 in early Wallerian degeneration, which may provide new insights into the molecular mechanisms of Wallerian degeneration.

Acupuncture at Baihui (GV20) and Dazhui (GV14) reduces neuronal loss and attenuates ultra-structural damage in cerebral ischemic rats. However, whether acupuncture can treat addiction and prevent readdiction through changes to brain cell ultrastructure remains unknown. In this study, cell apoptosis was observed in the hippocampus and frontal lobe of heroin readdicted rats by electron microscopy. Immunohistochemical staining displayed a reduction in Bcl-2 ex-pression and an increase in Bax expression in the hippocampus and frontal lobe. After rats were given acupuncture at Baihui and Dazhui, the pathological damage in the hippocampus and frontal lobe was signiifcantly reduced, Bcl-2 expression was upregulated and Bax expression was downregulated. Acupuncture exerted a similar effect with methadone, a commonly used drug for clinical treatment of drug addiction. Experimental ifndings suggest that acupuncture at Dazhui and Baihui can prevent brain cell apoptosis in heroin readdicted rats.

A chemically extracted acellular allogeneic nerve graft can reduce postoperative immune re-jection, similar to an autologous nerve graft, and can guide neural regeneration. However, it remains poorly understood whether a chemically extracted acellular allogeneic nerve graft combined with neurotrophic factors provides a good local environment for neural regenera-tion. This study investigated the repair of injured rat sciatic nerve using a chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor. An autologous nerve anastomosis group and a chemical acellular allogeneic nerve bridging group were prepared as controls. At 8 weeks after repair, sciatic functional index, evoked potential amplitude of the soleus muscle, triceps wet weight recovery rate, total number of myelinated nerve fibers and myelin sheath thickness were measured. For these indices, values in the three groups showed the autologous nerve anastomosis group > chemically extracted acellular nerve graft + ciliary neurotrophic factor group > chemical acellular allogeneic nerve bridging group. These results suggest that chemically extracted acellular nerve grafts combined with ciliary neurotrophic factor can repair sciatic nerve defects, and that this repair is inferior to autologous nerve anasto-mosis, but superior to chemically extracted acellular allogeneic nerve bridging alone.

Neural stem cell transplantation is a useful treatment for ischemic stroke, but apoptosis often occurs in the hypoxic-ischemic environment of the brain after cell transplantation. In this study, we determined if mild hypothermia (27-28°C) can increase the survival rate of neural stem cells (1.0 × 105 /μL) transplanted into neonatal mice with hypoxic-ischemic encephalopathy. Long-term effects on neurological functioning of the mice were also examined. After mild hy-pothermia combined with neural stem cell transplantation, we observed decreased expression levels of inflammatory factor nuclear factor-kappa B and apoptotic factor caspase-3, reduced cerebral infarct volumes, increased survival rate of transplanted cells, and marked improvements in neurological function. Thus, the neuroprotective effects of mild hypothermia combined with neural stem cell transplantation are superior to those of monotherapy. Moreover, our ifndings suggest that the neuroprotective effects of mild hypothermia combined with neural stem cell transplantation on hypoxic-ischemic encephalopathy are achieved by anti-inlfammatory and an-ti-apoptotic mechanisms.

In this study, we developed a novel artiifcial nerve graft termed self-assembling peptide nanoifber scaffold (SAPNS)-containing poly(lactic-co-glycolic acid) (PLGA) conduit (SPC) and used it to bridge a 10-mm-long sciatic nerve defect in the rat. Retrograde tracing, behavioral testing and histomorphometric analyses showed that compared with the empty PLGA conduit implanta-tion group, the SPC implantation group had a larger number of growing and extending axons, a markedly increased diameter of regenerated axons and a greater thickness of the myelin sheath in the conduit. Furthermore, there was an increase in the size of the neuromuscular junction and myoifber diameter in the target muscle. These ifndings suggest that the novel artiifcial SPC nerve graft can promote axonal regeneration and remyelination in the transected peripheral nerve and can be used for repairing peripheral nerve injury.

Compound Formula Rehmannia has been shown to be clinically effective in treating Parkin-son’s disease and levodopa-induced dyskinesia;however, the mechanisms remain unclear. In this study, we established a model of Parkinson’s disease dyskinesia in rats, and treated these animals with Compound Formula Rehmannia. Compound Formula Rehmannia inhibited the increase in mRNA expression of N-methyl-D-aspartate receptor subunits 1 and 2 and excitatory amino acid neurotransmitter genes, and it inhibited the reduction in expression of γ-aminobutyric acid receptor B1, an inhibitory amino acid neurotransmitter gene, in the corpus striatum. In addition, Compound Formula Rehmannia alleviated dyskinesia symptoms in the Parkinson’s disease rats. These experimental findings indicate that Compound Formula Rehmannia alleviates levodo-pa-induced dyskinesia in Parkinson’s disease by modulating neurotransmitter signaling in the corpus striatum.

There are currently no federally approved neuroprotective agents to treat traumatic brain injury. Progesterone, a hydrophobic steroid hormone, has been shown in recent studies to exhibit neu-roprotective effects in controlled cortical impact rat models. Akt is a protein kinase known to play a role in cell signaling pathways that reduce edema, inlfammation, apoptosis, and promote cell growth in the brain. This study aims to determine if progesterone modulates the phosphor-ylation of Aktvia its threonine 308 phosphorylation site. Phosphorylation at the threonine 308 site is one of several sites responsible for activating Akt and enabling the protein kinase to carry out its neuroprotective effects. To assess the effects of progesterone on Akt phosphorylation, C57BL/6 mice were treated with progesterone (8 mg/kg) at 1 (intraperitonally), 6, 24, and 48 hours (subcutaneously) post closed-skull traumatic brain injury. The hippocampus was harvest-ed at 72 hours post injury and prepared for western blot analysis. Traumatic brain injury caused a signiifcant decrease in Akt phosphorylation compared to sham operation. However, mice treat-ed with progesterone following traumatic brain injury had an increase in phosphorylation of Akt compared to traumatic brain injury vehicle. Our ifndings suggest that progesterone is a viable treatment option for activating neuroprotective pathways after traumatic brain injury.

Ginsenoside Rd has a clear neuroprotective effect against ischemic stroke. We aimed to verify the neuroprotective effect of ginsenoside Rd in spinal cord ischemia/reperfusion injury and explore its anti-apoptotic mechanisms. We established a spinal cord ischemia/reperfusion injury model in rats through the occlusion of the abdominal aorta below the level of the renal artery for 1 hour. Successfully established models were injected intraperitoneally with 6.25, 12.5, 25 or 50 mg/kg per day ginsenoside Rd. Spinal cord morphology was observed at 1, 3, 5 and 7 days after spinal cord ischemia/reperfusion injury. Intraperitoneal injection of ginsenoside Rd in ischemia/reperfusion injury rats not only improved hindlimb motor function and the morphology of motor neurons in the anterior horn of the spinal cord, but it also reduced neuronal apoptosis. The optimal dose of ginsenoside Rd was 25 mg/kg per day and the optimal time point was 5 days after ischemia/reperfusion. Immunohistochemistry and western blot analysis showed ginsenoside Rd dose-de-pendently inhibited expression of pro-apoptotic Caspase 3 and down-regulated the expression of the apoptotic proteins ASK1 and JNK in the spinal cord of rats with spinal cord ischemia/reper-fusion injury. These ifndings indicate that ginsenoside Rd exerts neuroprotective effects against spinal cord ischemia/reperfusion injury and the underlying mechanisms are achieved through the inhibition of ASK1-JNK pathway and the down-regulation of Caspase 3 expression.

In this study, we established cell models for Parkinson’s disease using rotenone. An RNA interfer-ence vector targeting Parkin-associated endothelin receptor-like receptor (Pael-R) was transfected into the model cells. The results of reverse-transcription polymerase chain reaction and western blot analysis showed that Pael-R expression was decreased after RNA interference compared with the control group (no treatment) and the model group (rotenone treatment), while the rate of apoptosis and survival of dopaminergic cells did not differ signiifcantly between groups, as de-tected by lfow cytometry and an MTT assay. These experimental ifndings indicate that the Pael-R gene has no role in the changes in rotenone-induced Parkinson’s disease model cells.

Tongxinluo has been widely used in China for the treatment of acute stroke and for neu-roprotection. However, there are few positron emission tomography (PET) studies on the neuroprotective effect ofTongxinluo on cerebral ischemia/reperfusion in small animals. In the present study,Tongxinluosuperfine powder suspension or its vehicle was administered intragastrically to rats for 5 successive days before middle cerebral artery occlusion.18F-lfuo-rodeoxyglucose (FDG) small animal PET imaging showed that at 1 and 2 weeks after cerebral ischemia/reperfusion, glucose metabolism in the ischemic area was greater in rats that had receivedTongxinluo than in those that had received the vehicle. Nissl staining showed that 2 weeks after cerebral ischemia/reperfusion, there was less neuronal loss in the prefrontal cortex in Tongxinluo-treated rats than in controls. In addition,Tongxinluo-treated animals showed better neurologic function and lower cerebral infarct volume than rats that received the vehicle. These findings suggest thatTongxinluo exhibits neuroprotective effects in cerebral ischemia/reper-fusion injury and demonstrates that18F-FDG small animal PET imaging is a useful tool with which to study the molecular pharmacology of traditional Chinese medicine.

To investigate the effect of early rehabilitation on neurofunctional outcome after surgery in chil-dren with spinal tumors, this study reviewed the medical charts and radiographic records of 70 pediatric patients (1-17 years old) who received spinal tumor surgical removal. The peddiatric patients received rahabilitation treatment at 4 (range, 2-7) days after surgery for 10 (range, 7-23) days. Results from the Modiifed McCormick Scale, Functional Independence Measure for Chil-dren, American Spinal Injury Association Impairment Scale and Karnofsky Performance Status Scale demonstrated that the sensory function, motor function and activity of daily living of pedi-atric children who received early rehabilitation were signiifcantly improved. Results also showed that tumor setting and level localization as well as patients’s clinical symptoms have no inlfuences on neurofunctional outcomes.

Previous studies have conifrmed that heat shock protein 90 overexpression can lead to dopami-nergic neuronal death. This study was designed to further investigate what effects are produced by heat shock protein 90 after endurance exercise training. Immunohistochemistry results showed that exercise training signiifcantly inhibited heat shock protein 90 overexpression in the soleus and gastrocnemius in Parkinson’s disease rats, which is a potential therapeutic target for ameliorating skeletal muscle abnormalities in Parkinson’s disease.

Shuganjieyu capsule has been approved for clinical treatment by the State Food and Drug Ad-ministration of China since 2008. In the clinic, Shuganjieyu capsule is often used to treat mild to moderate depression. In the rat model of depression established in this study, Shuganjieyu capsule was administered intragastrically daily before stress. Behavioral results conifrmed that depressive symptoms lessened after treatment with high-dose (150 mg/kg) Shuganjieyu capsule. Immunohistochemistry results showed that high-dose Shuganjieyu capsule signiifcantly increased phosphorylation levels of phosphorylation cyclic adenosine monophosphate response element binding protein and brain-derived neurotrophic factor expression in the medial prefrontal cortex and hippocampal CA3 area. Overall, our results suggest that in rats, Shuganjieyu capsule effec-tively reverses depressive-like behaviors by increasing expression levels of neurotrophic factors in the brain.

We have previously shown that Achyranthes bidentata polypeptides (ABPP), isolated from Achy-ranthes bidentata Blume (a medicinal herb), exhibit neurotrophic and neuroprotective effects on the nervous system. To identify the major active component of ABPP, and thus optimize the use of ABPP, we used reverse-phase high performance liquid chromatography to separate ABPP. We ob-tained 12 fractions, among which the fraction of ABPPk demonstrated the strongest neuroactivity. Immunocytochemistry and western blot analysis showed that ABPPk promoted neurite growth in cultured dorsal root ganglion explant and dorsal root ganglion neurons, which might be associated with activation of Erk1/2. A combination of behavioral tests, electrophysiological assessment, and histomorphometric analysis indicated that ABPPk enhanced nerve regeneration and function res-toration in a mouse model of crushed sciatic nerve. All the results suggest that ABPPk, as the key component of ABPP, can be used for peripheral nerve repair to yield better outcomes than ABPP.

This study investigated the possible involvement of microRNAs in the regulation of genes that participate in peripheral neural regeneration. A microRNA microarray analysis was conducted and 23 microRNAs were identiifed whose expression was signiifcantly changed in rat dorsal root ganglia after sciatic nerve transection. The expression of one of the downregulated microRNAs, microRNA-214, was validated using quantitative reverse transcriptase-PCR. MicroRNA-214 was predicted to target the 3′-untranslated region of Slit-Robo GTPase-activating protein 3. In situ hybridization veriifed that microRNA-214 was located in the cytoplasm of dorsal root ganglia primary neurons and was downregulated following sciatic nerve transection. Moreover, a com-bination of in situ hybridization and immunohistochemistry revealed that microRNA-214 and Slit-Robo GTPase-activating protein 3 were co-localized in dorsal root ganglion primary neu-rons. Western blot analysis suggested that Slit-Robo GTPase-activating protein 3 was upregulated in dorsal root ganglion neurons after sciatic nerve transection. These data demonstrate that mi-croRNA-214 is located and differentially expressed in dorsal root ganglion primary neurons and may participate in regulating the gene expression of Slit-Robo GTPase-activating protein 3 after sciatic nerve transection.

Previous studies have shown that proliferation of endogenous neural precursor cells cannot alone compensate for the damage to neurons and axons. From the perspective of neural plastici-ty, we observed the effects of functional electrical stimulation treatment on endogenous neural precursor cell proliferation and expression of basic fibroblast growth factor and epidermal growth factor in the rat brain on the infarct side. Functional electrical stimulation was performed in rat models of acute middle cerebral artery occlusion. Simultaneously, we set up a placebo stimulation group and a sham-operated group. Immunohistochemical staining showed that, at 7 and 14 days, compared with the placebo group, the numbers of nestin (a neural precursor cell marker)-positive cells in the subgranular zone and subventricular zone were increased in the functional electrical stimulation treatment group. Western blot assays and reverse-transcription PCR showed that total protein levels and gene expression of epidermal growth factor and basic ifbroblast growth factor were also upregulated on the infarct side. Prehensile traction test results showed that, at 14 days, prehension function of rats in the functional electrical stimulation group was signiifcantly better than in the placebo group. These results suggest that functional electrical stimulation can promote endogenous neural precursor cell proliferation in the brains of acute cerebral infarction rats, enhance expression of basic fibroblast growth factor and epidermal growth factor, and improve the motor function of rats.

Motor reinnervation after repair of tibial nerve defects using autologous vein grafts in rats has previously been reported, but sensory reinnervation after the same repair has not been fully investigated. In this study, partial sensory reinnervation of muscle spindles was observed after repair of 10-mm left tibial nerve defects using autologous vein grafts with end-to-end anasto-mosis in rats, and functional recovery was conifrmed by electrophysiological studies. There were no signiifcant differences in the number, size, or electrophysiological function of reinnervated muscle spindles between the two experimental groups. These ifndings suggest that repair of short nerve defects with autologous vein grafts provides comparable results to immediate end-to-end anastomosis in terms of sensory reinnervation of muscle spindles.