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To investigate the correlation between the behavioral performance and the expressions of substance P (SP) and neurokinin-1 receptor (NK-1R) in the posterior horn of the L5－S2 spinal cord in rats with chronic prostatitis (CP).A CP model was made in 30 adult male SD rats by intraperitoneal injection of 0.5 ml dyphtheria pertussis tetanus (DPT) vaccine and mixed solution of 1 ml prostatein extract and complete adjuvant in a 1∶1 ratio, and another 10 rats were injected with the same volume of normal saline as controls. At 45 (n = 10), 60 (n = 10) and 90 days (n = 10) after modeling, the behavioral changes of the rats were observed by open-field and sucrose consumption tests, the prostatic indexes and levels of serum TNF-α, IL-1β, IL-2 and IL-10 were obtained, and the expressions of SP and NK1-R in the L5－S2 spinal cord were determined by immunohistochemistry.Compared with the controls, the CP model rats showed obviously decreased horizontal and vertical movement scores and sucrose consumption, particularly in the 90 d group (P0.05), significantly reduced prostatic indexes in the 45 d, 60 d and 90 d groups (all P0.05), even lower in the 90 d than in the 45 d and 60 d groups (P0.05). Edema and lymphocytes were increased in the prostatic tissue with the prolonged time of modeling. The levels of serum TNF-α, IL-1β, IL-2 and IL-10 were markedly elevated in all the CP rats as compared with those in the controls (P0.05), and so were the expressions of SP and NK-1R in the L5－S2 spinal cord (P0.05), even more significantly in the 90 d than in the 45 d and 60 d groups (P0.05).Rats with chronic prostatitis are characterized by behavioral manifestation of depression, increased levels of serum TNF-α, IL-1β, IL-2 and IL-10, and a time-dependent upregulation of the expressions of SP and NK-1R in the posterior horn of the L5-S2 spinal cord, which suggests a correlation between the behavioral performance and the expressions of SP and NK-1R in the L5－S2 spinal cord of the rats.

Electrical excitability by membrane depolarization is crucial for survival and maturation of newborn cells in the dentate gyrus of the hippocampus. However, traditional technology for membrane depolarization lacks temporal and spatial precision. Optogenetics can be used to activate channelrhodopsin-2 (ChR2), allowing cationic current to depolarize genetically targeted cells. In this study, we used ChR2-EGFP driven by doublecortin (DCX) to promote survival and maturation of newborn cells in the dentate gyrus after traumatic brain injury (TBI). C57BL/6 mice underwent lateral fluid percussion TBI. TBI mice were transfected with a lentivirus carrying the DCX-ChR2-EGFP gene. We observed that not only immature neurons but also type-2b intermediate progenitor (IPs) and neuroblasts expressed DCX-EGFP, indicating that DCX-expressing newborn cells could provide a long time window for electrical activity regulation. Quantitative results showed that the number of EGFP-expressing cells began to rise at 3 days after TBI and peaked at 9 days after TBI. By optical depolarization of DCX-EGFP-expressing cells between 3 and 12 days, we observed significantly improved cognitive deficits after TBI with enhanced survival and maturation of newborn cells in the dentate gyrus. We also investigated the role of optical depolarization in neural stem cells transfected with a lentivirus carrying the ChR2-DCX-EGFP gene in vitro. By administrating verapamil to block L-type calcium channels, we verified that the up-regulation of MAP2, NeuN, Neurog2, NeuroD1 and GluR2 in newborn cells was mediated by ChR2-elicted depolarization. By using β-catenin inhibitor Dkk1, we demonstrated that optical depolarization of DCX-EGFP-expressing cells facilitated survival and maturation probably through the Wnt/β-catenin signaling cascade.

The secretome of mesenchymal stem cell (MSC) offers a series of immunoregulatory properties and is regarded as an effective method of mitigating secondary neuroinflammation induced by traumatic brain injury (TBI). The secretome of adipose-derived MSCs (ASC-ST) was collected under hypoxia conditions. Proteomics data were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and concentrations of major components were tested. After the TBI caused by an electric cortical contusion impactor, rats were injected ASC-ST through caudal veins for 7 days. The neurological functional prognosis of TBI rats was significantly improved, and the vasogenic edema of brain tissues that was measured 14 days after TBI was relieved by ASC-ST, corresponding to brain water content levels. ASC-ST ameliorated TBI-induced neuroinflammatory environments that caused the edema, the apoptosis of the neural cells, and the nerve fiber damage by increasing the number of M2 phenotypes present while reducing the number of M1 phenotype microglia present. Furthermore, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels were reduced, whereas transforming growth factor-beta (TGF-β) and tumor necrosis factor-stimulated gene 6 protein (TSG-6) levels were increased after secretome treatment. Altogether, ASC-ST is capable of improving neural functioning by modulating TBI-induced neuroinflammation and its related secondary insults. ASC-ST may be one of the most promising candidates for regulating the secondary inflammatory reactions of central nervous systems for clinical use.

Although previous research has demonstrated that traumatic brain injury (TBI) accelerates the proliferation of neural stem cells in dentate gyrus of the hippocampus, most of these newborn cells undergo apoptosis in a traumatic microenvironment. Thus, promoting the long-term survival of newborn cells during neurogenesis is a compelling goal for the treatment of TBI. In this study, we investigated whether mild hypothermia (MHT) therapy, which mitigates the multiple secondary injury cascades of TBI, enhances the survival of newborn cells. SD rats were subjected to unilateral fluid percussion injury and received MHT therapy for 4 h (33.5 °C). Bromodeoxyuridine (BrdU) was administered to label the mitotic cells. Spatial learning and memory were evaluated with the Morris water maze test. Brain sections were immunostained with antibodies against BrdU, DCX (a neuroblast marker) or NeuN (a mature neuron marker). The apoptosis levels in the dentate gyrus were examined with antibodies against the apoptotic proteins FAS, FASL, Bcl-2 and cleaved caspase 3. The results indicated that MHT could significantly prevent TBI-induced cognitive impairments. At 1 week after injury, the density of BrdU-immunoreactive cells significantly increased in both TBI and TBI + MHT rats. At 4 weeks after injury, the density of BrdU-positive cells further increased in TBI + MHT rats, whereas the density declined in the TBI rats. The density of DCX-positive cells in SGZ of the hippocampus at 1 week after injury in the TBI + MHT rats was significantly greater than in the TBI rats. Moreover, the density of NeuN-positive cells in the subgranular zone at 4 weeks after injury and in the granule cell layer at 7 weeks after injury was significantly increased in the TBI + MHT rats. The TBI + MHT rats displayed a lower level of apoptosis in the dentate gyrus compared with the TBI rats. These data indicate that TBI could only facilitate a burst of proliferation and short-term survival of newborn cells, whereas TBI + MHT could facilitate long-term survival and maturation of newborn cells through diminishing pro-apoptotic microenvironment. These results suggest that MHT-mediated neurogenesis may have an important therapeutic potential for the endogenous repair of TBI.

Both chemical and physical microenvironments appear to be important for lineage specification of umbilical cord mesenchymal stem cells (UCMSCs). However, physical factors such as the elastic modulus in traumatic brain injury (TBI) are seldom studied. Intracranial hypertension and cerebral edema after TBI may change the brain's physical microenvironment, which inhibits neural lineage specification of transplanted UCMSCs. The purpose of this study is to investigate the potential regulatory effect of mild hypothermia on the elastic modulus of the injured brain. First, we found that more UCMSCs grown on gels mimicking the elastic modulus of the brain (0.5 kPa) differentiated into neural cells, which were verified with the formation of branched cells and the expression of neural markers. Then, UCMSCs were transplanted into TBI rats, and we observed that mild hypothermia resulted in the differentiation of more neurons and astrocytes from transplanted UCMSCs. To demonstrate that more neural specification of UCMSCs was due to the regulation of the elastic modulus, we monitored intracranial pressure and cerebral edema. The results showed that mild hypothermia significantly reduced intracranial pressure and brain water content, indicating modulation of the elastic modulus by mild hypothermia. An examination with atomic force microscopy (AFM) in a cell injury model in vitro further verified hypothermia-regulated elastic modulus. In this study, we found a novel role of mild hypothermia in modulating the elastic modulus of the injured brain, resulting in the promotion of neural lineage specification of UCMSCs, which suggested that the combination of mild hypothermia had more advantages in cell-based therapy after TBI.

Although hypothermic-targeted temperature management (HTTM) holds great potential for the treatment of traumatic brain injury (TBI), translation of the efficacy of hypothermia from animal models to TBI patientshas no entire consistency. This study aimed to find an ideal time window model in experimental rats which was more in accordance with clinical practice through the delayed HTTM intervention. Sprague-Dawley rats were subjected to unilateral cortical contusion injury and received therapeutic hypothermia at 15mins, 2 h, 4 h respectively after TBI. The neurological function was evaluated with the modified neurological severity score and Morris water maze test. The brain edema and morphological changes were measured with the water content and H&E staining. Brain sections were immunostained with antibodies against DCX (a neuroblast marker) and GFAP (an astrocyte marker). The apoptosis levels in the ipsilateral hippocampi and cortex were examined with antibodies against the apoptotic proteins Bcl-2, Bax, and cleaved caspase-3 by the immunofluorescence and western blotting. The results indicated that each hypothermia therapy group could improve neurobehavioral and cognitive function, alleviate brain edema and reduce inflammation. Furthermore, we observed that therapeutic hypothermia increased DCX expression, decreased GFAP expression, upregulated Bcl-2 expression and downregulated Bax and cleaved Caspase-3 expression. The above results suggested that HTTM at 2h or even at 4h post-injury revealed beneficial brain protection similarly, despite the best effect at 15min post-injury. These findings may provide relatively ideal time window models, further making the following experimental results more credible and persuasive.

Baicalin is one bioactive flavone with anti-inflammatory and neuroprotective activities. The neuroprotective effects of baicalin on pathological changes and behavioral deficits were explored in a mouse model of amyloid β (Aβ)(1-42) protein-induced Alzheimer's disease (AD). Mice received a bilateral injection of Aβ(1-42) protein into the hippocampus, then they were treated with baicalin (30, 50 and 100 mg/kg body weight, orally) or Tween 80. The therapeutic effects of baicalin were monitored by Morris water maze trial and probe test. Then mice were sacrificed for immunohistochemistry and western blot analysis. After a relatively short-term treatment of 14 days, 100 mg/kg of baicalin significantly ameliorated memory impairment in the Morris water maze test and probe test, and also attenuated glial cell activations and increase of TNF-α and IL-6 expressions induced by Aβ(1-42) protein. These results suggest that baicalin ameliorated Aβ(1-42) protein-related pathology and cognitive dysfunction via its anti-neuroinflammatory activity, and may be a potential candidate for the treatment of AD.

To evaluate the efficacy and safety of linezolid in the treatment of post-neurosurgical intracranial methicillin-resistant Staphylococcus (MRS) infection.The data from 14 patients, admitted to neurological intensive care unit (ICU) of Medical College of Chinese People's Armed Police Forces between March 2009 and November 2011, were retrospectively analyzed. All these cases suffered from post-neurosurgical intracranial infection by MRS and received linezolid treatment. Blood and cerebrospinal fluid (CSF) were collected before and 7 days and 14 days after treatment for routine and bacteriological examinations to assess clinical efficacy and adverse reactions of linezolid.After 14-day treatment with linezolid, the clinical and laboratory parameters showed significant improvement: glucose (mmol/L) in CSF rose from 1.00 (0.65) to 3.15 (1.60), protein (mg/L) in CSF dropped from 2238.50 (2072.50) to 606.50 (217.30), white blood cell count [×10⁶/L] in CSF fell from 920.00 (1587.50) to 30.00 (40.00), and the number of patients with CSF neutrophil ratio0.20 was reduced from 14 to 1 (all P0.01). In addition, serum procalcitonin level (μg/L) was significantly reduced from 0.65 (1.16) to 0.08 (0.09) after linezolid therapy (P0.01). Total effective rate was 85.7% (12/14), and CSF bacterial clearance rate reached 100%. No adverse events were found during the treatment.Linezolid could effectively control post--neurosurgical intracranial MRS infection and alleviate the inflammatory responses with safety.

To study the underlying mechanism of acupuncture of "Zusanli" (ST 36) in clinical treatment of spleen deficiency syndrome (SDS).Twenty-six adult male Wistar rats were randomized into normal control group (n=6), model group (n=8), saline + model (saline) group (n=6) and acupuncture + model (acupuncture) group (n=6). The spleen deficiency syndrome model was duplicated by intragastric perfusion of 50% alcohol (1 mL/100 g, once) and vinegar (pH 3, 1 mL/100 g, once daily for 10 d). Bilateral "Zusanli" (ST 36) was punctured with filiform needles which were manipulated for 1 min after insertion and retained for 20 min. The treatment was conducted once daily for 10 days. The contents of serum testosterone(T) and estradiol(E2)were detected by radioimmunoassay. The rats' physical strength was detected by exhausted swimming test in cool water.In comparison with the normal group, the duration of exhausted swimming, serum T and E2 contents and T/E, were decreased significantly in the model group (P0.05). Compared with the model group, the duration of exhausted swimming, serum T and E2 contents and T/E2 in the acupuncture group were upregulated significantly (P0.05). No significant differences were found between the saline and control groups (P0.05).Acupuncture of "Zusanli" (ST 36) is able to reverse SDS-induced decrease of sexual hormones in spleen deficiency syndrome rats, which may contribute to its effect in improving physical strength.