The miR-9-5p/CXCL11 pathway is a key target of hydrogen sulfide-mediated inhibition of neuroinflammation in hypoxic ischemic brain injury

We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.

Alterations in gut microbiota are related to metabolite profiles in spinal cord injury

Studies have shown that gut microbiota metabolites can enter the central nervous system via the blood-spinal cord barrier and cause neuroinflammation, thus constituting secondary injury after spinal cord injury. To investigate the correlation between gut microbiota and metabolites and the possible mechanism underlying the effects of gut microbiota on secondary injury after spinal cord injury, in this study, we established mouse models of T8–T10 traumatic spinal cord injury. We used 16 S rRNA gene amplicon sequencing and metabolomics to reveal the changes in gut microbiota and metabolites in fecal samples from the mouse model. Results showed a severe gut microbiota disturbance after spinal cord injury, which included marked increases in pro-inflammatory bacteria, such as Shigella, Bacteroides, Rikenella, Staphylococcus, and Mucispirillum and decreases in anti-inflammatory bacteria, such as Lactobacillus, Allobaculum, and Sutterella. Meanwhile, we identified 27 metabolites that decreased and 320 metabolites that increased in the injured spinal cord. Combined with pathway enrichment analysis, five markedly differential amino acids(L-leucine, L-methionine, L-phenylalanine, L-isoleucine and L-valine) were screened out, which play a pivotal role in activating oxidative stress and inflammatory responses following spinal cord injury. Integrated correlation analysis indicated that the alteration of gut microbiota was related to the differences in amino acids, which suggests that disturbances in gut microbiota might participate in the secondary injury through the accumulation of partial metabolites that activate oxidative stress and inflammatory responses. Findings from this study provide a new theoretical basis for improving the secondary injury after spinal cord injury through fecal microbial transplantation.

Potentially fatal electrolyte imbalance caused by severe hydrofluoric acid burns combined with inhalation injury: A case report

BACKGROUND Hydrofluoric acid(HF)is one of the most common causes of chemical burns.HF burns can cause wounds that deepen and progress aggressively.As a result,HF burns are often severe even if they involve a small area of the skin.Published cases of HF burns have mostly reported small HF burn areas.Few cases of HF inhalation injury have been reported to date.CASE SUMMARY A 24-year-old man suffered from extensive hydrofluoric acid burns covering 60%of the total body surface area(TBSA),including deep second degree burns on 47%and third degree burns on 13%of the TBSA,after he fell into a pickling pool containing 15%HF.Comprehensive treatments were carried out after the patient was admitted.Ventricular fibrillation occurred 9 times within the first 2 h,and the lowest serum Ca2+concentration was 0.192 mmol/L.A dose of calcium gluconate(37 g)was intravenously supplied during the first 24 h,and the total amount of calcium gluconate supplementation was 343 g.Extracorporeal membrane oxygenation(ECMO)was applied for 8 d to handle the acute respiratory distress syndrome(ARDS)induced by the HF inhalation injury.The patient was discharged after 99 d of comprehensive treatment,including skin grafting.CONCLUSION Extensive HF burns combined with an inhalation injury led to a potentially fatal electrolyte imbalance and ARDS.Adequate and timely calcium supplementation and ECMO application were the keys to successful treatment of the patient.

Pharmacological treatment of inhalation injury after nuclear or radiological incidents: The Chinese and German approach

Inhalation injury is often associated with burns and significantly increases morbidity and mortality. The main toxic components of fire smoke are carbon monoxide, hydrogen cyanide, and irritants. In the case of an incident at a nuclear power plant or recycling facility associated with fire, smoke may also contain radioactive material. Medical treatments may vary in different countries, and in this paper, we discuss the similarities and differences in the treatments between China and Germany. Carbon monoxide poisoning is treated by 100% oxygen administration and,if available, hyperbaric oxygenation in China as well as in Germany. In addition, antidotes binding the cyanide ions and relieving the respiratory chain are important. Methemoglobin-forming agents(e.g., nitrites, dimethylaminophenol)or hydroxocobalamin(Vitamin B12) are options. The metabolic elimination of cyanide may be enhanced by sodium thiosulfate. In China, sodium nitrite with sodium thiosulfate is the most common combination. The use of dimethylaminophenol instead of sodium nitrite is typical for Germany, and hydroxocobalamin is considered the antidote of choice if available in cases of cyanide intoxications by fire smoke inhalation as it does not further reduce oxygen transport capacity. Systematic prophylactic use of corticosteroids to prevent toxic pulmonary edema is not recommended in China or Germany. Stable iodine is indicated in the case of radioiodine exposure and must be administered within several hours to be effective. The decorporation of metal radionuclides is possible with Ca(DTPA)or Prussian blue that should be given as soon as possible. These medications are used in both countries, but it seems that Ca(DTPA) is administered at lower dosages in China. Although the details of the treatment of inhalation injury and radionuclide(s) decorporation may vary, the general therapeutic strategy is very similar in China and Germany.

The therapeutic mechanism of dexamethasone in lung injury induced by hydrogen sulfide

The lung is one of the primary target organs of hydrogen sulfide(H2S),as exposure to H2S can cause acute lung injury(ALI)and pulmonary edema.Dexamethasone(Dex)exerts a protective effect on ALI caused by exposure to toxic gases and is commonly used in the clinic;however,the underlying mechanisms remain elusive,and the dose is unclear.Methods:In vivo experiments:divided C57BL6 mice into 6 groups at random,12 in each group.The mice were exposed to H2S for 3 h and 5 or 50 mg/kg Dex pretreated before exposure,sacrificed 12 h later.The morphological changes of HE staining and the ultrastructural changes of lungs under transmission electron microscopy were evaluated.The wet/dry ratio of lung tissue was measured.Bronchial alveolar lavage fluid(BALF)protein content and lung permeability index were detected.The expression of AQP5 protein was measured by immunohistochemistry and Western Blot(WB).In vitro experiments:divided human lung adenocarcinoma cell line A549 into 4 groups.1μmol/L dexamethasone was added to pre-incubation.The WB analyzed the protein of p-ERK1/2,p-JNK,and p-p38 in MAPK pathway after 1 h of NaHS exposure;six hours after NaHS exposure,the AQP5 protein was measured by WB.Results:Dex treatment could significantly attenuate the H2S-induced destruction to the alveolar wall,increase the wet-to-dry weight ratio and decrease pulmonary permeability index,with high-dose dexamethasone seemingly functioning better.Additionally,our previous studies showed that aquaporin 5(AQP 5),a critical protein that regulates water flux,decreased both in a mouse and cell model following the exposure to H2S.This study indicates that tThe decrease in AQP 5 can be alleviated by Dex treatment.Additionally,the mitogen activated protein kinase(MAPK)pathway may be involved in the protective effects of Dex in ALI caused by exposure to H2S since H2Sinduced MAPK activation could be inhibited by Dex.Conclusion:The present results indicate that AQP 5 may be considered a therapeutic target for Dex in H2S or other hazardous gases-induced ALI.

Effects of tetrandrine on the changes of free calcium level in neutrophils after smoke inhalation injury in the rabbit

The changes of the cytoplasmic free calcium level in the neutrophils after smoke in-halation injury were observed in rabbits and then the effects of tetrandrine,a calcium antago-nist,on the changes of free calcium level were studied.It was found that the number of neu-trophils increased significantly preceded by a transient decrease in the blood and also increasedin the bronehoalveolar lavage fluid after smoke inhalation.and the level of cytoplasmic free calci-um in the blood neutrophil increased likewise.Administration of tetrandrine resulted in a reduc-tion of the neutrophils number in the lungs and the free calcium level in the blood neutrophils toalleviate the pulmonary injury due to smoke inhalation.It is believed that there is a close rela-tionship between the activation of neutrophils and the pathophysiological changes of the lungs,and tetrandrine can exert its therapeutic effects on the injury by decreasing the free calcium levelin the neutrophils to modulate their functions.

Effects of Ginsenosides and Ketoprofen on Smoke Inhalation Injury in Rabbits and Rats

Six hours after smoke inhalation injury in rabbits, the permeability of pulmonary vesselsand the aggregation of circulating platelets increased markedly accompanied with apparent patholog-ical changes in the trachea and lungs. Fifteen minutes after smoke inhalation injury in rabbits, an intravenous dose of ginsenosides or ketoprofenwas given to the animals respectively. 6 hours after medication, it was found that both the drugscould significantly alleviate the platelet aggregation, but only ginsenosides could alleviate theaugmentation of pulmonary vascular permeability and the pathological lesions in the trachea andlungs. In those rats injured by smoke inhalation, l hour after an intravenous dose of ginsenosides, theplasma PGI2 level was elevated and TXA2/PGI2 ratio decreased significantly.

The Effects of Ginsenosides on Smoke Inhalation Injury in Rats

A rat model was used to explore the therapeutic effects of ginsenosides (GS)on smoke inhalation long injury.It was found that GS could markedly alleviate the in-crease of pulmonary microvascular permeability (PMVP),reduction of protein and leu-cocyte content in the bronchoalveolar lavage fluid (BALF) of the smoke inhalation injur-ed rats.Histopathological studies of the lungs revealed that GS could distinctly reduceleucocyte accumulation in the vessels,interstitial infiltration of leucocytes,interstitial andintra-alveolar edema,hemorrhage and vascular congestion.Meanwhile,GS could inhibitthe elevation of malondialdehyde (MDA) in the lungs and serum and reverse the decrea-sed activity of superoxide dismutase (SOD) in the lungs after smoke inhalation.In addi-tion experiments in vitro also showed the inhibition of lipid peroxidation in lung homo-genate and elimination of superoxide anions hydroxyl radicals effectively by GS in properdoses.These results imply that there is close interrelationship between the therapeuticefficiency of GS on smoke inhalation lung injury and its capability of antioxidation.

The Protective Effects of Preventive Atomisation Inhalation of Edaravone on the Lung Tissues of Rats with Smoke Inhalation Injury

Objective: To investigate the protective effects of the atomisation inhalation of edaravone on the lung tissues of rats with smoke inhalation injury. Methods: Forty male Sprague-Dawley (SD) rats were randomly divided into four groups of ten rats each: normal control group (group A), normal saline atomisation group (group B), edaravone aerosol group (group C) and edaravone atomisation prevention group (group D). Barring group A, the groups were used to create a model of severe smoke inhalation injury. However, before developing the model, group D rats were made to inhale edaravone (3.6 mg/mL) for 10 min. Six hours following smoke inhalation injury, abdominal artery blood samples were centrifuged, the lung tissue homogenate was prepared and carotid artery blood samples were used for blood gas analysis and oxygenation index (PaO2/FiO2) calculation. The levels of tumour necrosis factor alpha (TNF-α), interleukin (IL) 6 and IL-10 in serum and the levels of cysteine protease 3 (caspase-3), malondialdehyde (MDA), myeloperoxidase (MPO) and superoxide dismutase (SOD) in lung tissues were examined. The wet-dry ratio (W/D) and water content of the lung tissue were calculated, and the TUNEL method was used to determine the rate of lung tissue apoptosis in each group. Tissue specimens were obtained from the partial lung for histopathological examination. Results: Compared with those in group A, the water content of the lung tissue, the rate of lung tissue apoptosis, W/D and the caspase-3, TNF-α, IL-6, IL-10, MDA and MPO levels were significantly greater in other groups (PP< 0.05). Compared with those in group B, the levels of W/D, the water content of the lung tissue, the rate of lung tissue apoptosis and the levels of caspase-3, TNF-α, IL-6, MDA and MPO were significantly low (P and the levels of IL-10, SOD and PaO2/FiO2 were significantly high in groups C and D (P The expression of the aforementioned factors was more evident in Group D (P < 0.05). Histopathological examination revealed that groups C and D had greater levels of inflammatory granulocytes than group B. This was more evident in group D. Conclusions: The inhalation of edaravone can reduce smoke inhalation-induced lung injury. This may be related to the inhibition of apoptosis, the reduction of peroxidation injury and the production/release of inflammatory mediators/free radicals. It exerts a remarkable preventive effect.

The Association of Pneumonia with Clinical Outcome in Patients with Inhalation Injury

Introduction: Inhalation injury is a particularly lethal form of thermal burn injury, and is associated with increased morbidity and mortality. Pneumonia is a common complication of inhalation injury, due to the increased susceptibility of lungs that have been stripped of their biologic defense mechanisms, as well as the general susceptibility of the burn population to infections. While older series suggest that pneumonia is associated with worse mortality and morbidity, recent reports suggest that this may not be the case in all populations. Methods: We attempted to clarify the impact of pneumonia in terms of mortality, length of mechanical ventilation, need for tracheostomy, and discharge disposition, in patients admitted with inhalation injury by performing a retrospective review of patients admitted to a regional burn center 2002-2009. Burn registry and electronic chart review were used to obtain demographic, clinical and outcome data. Univariate and multivariate analysis was used to compare outcomes in patients who developed pneumonia versus those who did not. Results: The study cohort comprised 166 patients, of whom 21 (13%) were diagnosed with pneumonia. Development of pneumonia was not predicted by age, surface area burned or other complications such as acute respiratory distress syndrome. Surprisingly, pneumonia was associated with reduced inpatient mortality (p = 0.006). However, patients who developed pneumonia were also more likely to have prolonged ventilator dependence (19 vs 5 days,

黄芪甲苷对高剂量S-氯胺酮诱导PC12细胞损伤的保护作用

以高剂量S-氯胺酮(S-ketamine, SK)诱导PC12细胞构建体外神经损伤模型,探究黄芪甲苷(astragaloside IV,ASⅣ)对高剂量SK诱导PC12细胞损伤的保护作用及其机制。采用CCK-8法测定细胞活力,并以此确定SK的最佳造模浓度和ASⅣ的最佳治疗浓度;流式细胞术测定细胞凋亡率;DCFH-DA荧光探针法检测细胞内活性氧(ROS)的含量;qPCR法检测目的基因的表达;Western blot技术检测目的蛋白的表达。结果显示,SK的最佳造模浓度为450μg/mL,ASⅣ的最佳治疗浓度为25μmol/L;与对照组相比,SK组细胞凋亡率、ROS含量、Caspase-9和Cytochrome C mRNA表达水平均显著升高(P<0.05),Bax、Pro-Caspase-9、Cleaved-Caspase-9和Cytochrome C蛋白表达量同样显著上升(P<0.05),而Bcl-2/Bax mRNA表达水平比值、Bcl-2蛋白表达量显著下降(P<0.05);ASⅣ治疗后,明显逆转了高剂量SK诱导引起的各项指标变化(P<0.05)。这说明黄芪甲苷可以减轻高剂量S-氯胺酮所致PC12细胞损伤,其机制可能与抑制线粒体凋亡途径有关。

Effects of early bronchoalveolar lavage fluid collected from dogs with smoke inhalation injury on the lungs of rats

Objective: Whether early massive bronchoalveolar lavage can remove the harmful substances from the lungs injured with smoke inhalation remains uncertain. This study was designed to observe the effects of early massive bronchoalveolar lavage fluid (BALF) on the healthy lungs in rats. Methods: Mongrel dogs were inflicted with severe smoke inhalation injury. The injured lungs were lavaged with large amount of normal saline in the first hour after injury and the BALF was collected. The BALF was injected into the healthy lungs of 30 rats (group C) in the dosage of 5 ml/kg. The functions and pathological changes of the lungs were observed 24 h after perfusion with the BALF. The data were compared with those of 23 rats (group B) whose lungs were perfused with the BALF collected from normal dogs and those of 21 rats (group A) whose lungs were perfused with normal saline. Results: The mortality rate 24 h after lung perfusion was higher in group C than in groups A and B. The survivors of group C exhibited fluctuation of respiratory rate (RR), remarkable decrease of PaO 2, significantly higher content of lung water, decrease of total static pulmonary compliance and pulmonary expansion index, and increasse of inflammatory cytokines in the tissues of lungs. Only slight mechanic obstructive effect on the airway was observed in rats of group A and B. The pathological changes of the lungs of the rats in group C were similar to those of the dogs with actual smoke inhalation injury. Conclusion: Our findings indicate that the BALF collected from dogs with acute severe smoke inhalation injury in the early stage after injury injured the normal lungs of rats with the bioactive substances in the BALF. These findings show us that it is a valuable therapeutic procedure to apply massive bronchoalveolar fluid lavage in the early stage after inhalation injury.

高热惊厥患儿外周血NLR和H_(2)S水平变化及与脑损伤的相关性

目的探讨高热惊厥患儿外周血中性粒细胞/淋巴细胞比值(NLR)和硫化氢(H_(2)S)水平变化及与脑损伤的相关性。方法选取2021年1月至2023年1月期间本院收治的高热惊厥患儿共220例,其中单纯性153例纳入单纯性组,复杂性67例纳入复杂性组,同期选取高热无惊厥患儿109例纳入对照组。所有患儿均检测外周血NLR和H_(2)S水平,采用受试者工作特征(ROC)曲线鉴别单纯性及复杂性高热惊厥患儿。根据高热惊厥患儿有无脑损伤发生情况分为脑损伤组及无脑损伤组,收集两组高热惊厥患儿临床资料,采用多因素Logistic回归模型分析影响高热惊厥患儿脑损伤的独立危险因素。结果与对照组比较,单纯性组及复杂性组外周血NLR水平升高,H_(2)S水平降低(P<0.05),与单纯性组比较,复杂性组外周血NLR水平升高,H_(2)S水平降低(P<0.05)。ROC分析结果显示,外周血NLR、H_(2)S单独检测及二者联合检测鉴别单纯性及复杂性高热惊厥患儿的AUC值(95%CI)分别为0.615(0.547~0.680)、0.731(0.667~0.788)、0.827(0.771~0.875),NLR、H_(2)S联合检测的预测效能高于单独检测(Z=4.488、2.161,P<0.05)。脑损伤组惊厥时体温≥40℃、复杂性高热惊厥、惊厥发作次数≥2次、惊厥持续时间≥15 min例数占比、外周血NLR水平均高于无脑损伤组,H_(2)S水平低于无脑损伤组(P<0.05)。多因素Logistic回归模型分析结果显示,复杂性高热惊厥、惊厥发作次数≥2次,惊厥持续时间≥15 min、外周血NLR高水平及H_(2)S低水平是影响高热惊厥患儿发生脑损伤的独立危险因素(P<0.05)。结论高热惊厥患儿外周血NLR水平升高,H_(2)S水平降低,外周血NLR、H_(2)S水平对于高热惊厥患儿分型具有重要的鉴别价值,且与高热惊厥患儿脑损伤的发生密切相关。

Post electrical or lightning injury syndrome: a proposal for an American Psychiatric Association's Diagnostic and Statistical Manual formulation with implications for treatment

In the past, victims of electrical and lightning injuries have been assessed in a manner lacking a system- atic formulation, and against ad hoc criteria, particularly in the area of neuropsychological disability. In this manner patients have, for example, only been partially treated, been poorly or incorrectly diagnosed, and have been denied the full benefit of compensation for their injuries. This paper contains a proposal for diagnostic criteria particularly for the neuropsychological aspects of the post injury syndrome. It pays attention to widely published consistent descriptions of the syndrome, and a new cluster analysis of post electrical injury patients. It formulates a proposal which could be incorporated into future editions of the American Psychiatric Association＇s Diagnostic and Statistical Manual （DSM）. The major neuropsycholog- ical consequences include neurocognitive dysfunction, and memory subgroup dysfunction, with ongoing consequences, and sometimes including progressive or delayed psychiatric, cognitive, and/or neurological symptoms. The proposed diagnostic criteria insist on a demonstrated context for the injury, both specifying the shock circumstance, and also physical consequences. It allows for a certain delay in onset of symptoms. It recognizes exclusory conditions. The outcome is a proposal for a DSM classification for the post electrical or lightning injury syndrome. This proposal is considered important for grounding patient treatment, and for further treatment trials. Options for treatment in electrical or lightning injury are summarised, and future trials are foreshadowed.

S100B protein in serum is elevated after global cerebral ischemic injury

BACKGROUND:S100B protein in patients with cardiac arrest,hemorrhagic shock and other causes of global cerebral ischemic injury will be dramatically increased.Ischemic brain injury may elevate the level of serum S100 B protein and the severity of brain damage.METHODS:This article is a critical and descriptive review on S100 B protein in serum after ischemic brain injury.We searched Pubmed database with key words or terms such as "S100B protein", "cardiac arrest", "hemorrhagic shock" and "ischemia reperfusion injury" appeared in the last five years.RESULTS:S100B protein in patients with cardiac arrest,hemorrhagic shock and other causes of ischemic brain injury will be dramatically increased.Ischemic brain injury elevated the level of serum S100 B protein,and the severity of brain damage.CONCLUSION:The level of S100 B protein in serum is elevated after ischemic brain injury,but its mechanism is unclear.

Early electrical field stimulation prevents the loss of spinal cord anterior horn motoneurons and muscle atrophy following spinal cord injury

Our previous study revealed that early application of electrical field stimulation（EFS） with the anode at the lesion and the cathode distal to the lesion reduced injury potential, inhibited secondary injury and was neuroprotective in the dorsal corticospinal tract after spinal cord injury（SCI）. The objective of this study was to further evaluate the effect of EFS on protection of anterior horn motoneurons and their target musculature after SCI and its mechanism. Rats were randomized into three equal groups. The EFS group received EFS for 30 minutes immediately after injury at T_（10）. SCI group rats were only subjected to SCI and sham group rats were only subjected to laminectomy. Luxol fast blue staining demonstrated that spinal cord tissue in the injury center was better protected; cross-sectional area and perimeter of injured tissue were significantly smaller in the EFS group than in the SCI group. Immunofluorescence and transmission electron microscopy showed that the number of spinal cord anterior horn motoneurons was greater and the number of abnormal neurons reduced in the EFS group compared with the SCI group. Wet weight and cross-sectional area of vastus lateralis muscles were smaller in the SCI group to in the sham group. However, EFS improved muscle atrophy and behavioral examination showed that EFS significantly increased the angle in the inclined plane test and Tarlov＇s motor grading score. The above results confirm that early EFS can effectively impede spinal cord anterior horn motoneuron loss, promote motor function recovery and reduce muscle atrophy in rats after SCI.

Amyloid beta-peptide worsens cognitive impairment following cerebral ischemia-reperfusion injury

Amyloid 13-peptide, a major component of senile plaques in Alzheimer＇s disease, has been implicated in neuronal cell death and cognitive impairment. Recently, studies have shown that the pathogenesis of cerebral ischemia is closely linked with Alzheimer＇s disease. In this study, a rat model of global cerebral ischemia-reperfusion injury was established via occlusion of four arteries; meanwhile, fibrillar amyloid [3-peptide was injected into the rat lateral ventricle. The Morris water maze test and histological staining revealed that administration of amyloid 13-peptide could further aggravate impairments to learning and memory and neuronal cell death in the hippocampus of rats subjected to cerebral ischemia-reperfusion injury. Western blot showed that phosphorylation of tau protein and the activity of glycogen synthase kinase 313 were significantly stronger in cerebral ischemia-reperfusion injury rats subjected to amyloid [3-peptide administration than those undergo- ing cerebral ischemia-repetfusion or amyloid 13-peptide administration alone. Conversely, the activ- ity of protein phosphatase 2A was remarkably reduced in rats with cerebral ischemia-reperfusion injury following amyloid 13-peptide administration. These findings suggest that amyloid 13-peptide can potentiate tau phosphorylation induced by cerebral ischemia-reperfusion and thereby aggravate cognitive impairment.

Glial fibrillary acidic protein levels are associated with global histone H4 acetylation after spinal cord injury in rats

Emerging evidence has suggested global histone H4 acetylation status plays an important role in neural plasticity. For instance, the imbalance of this epigenetic marker has been hypothesized as a key factor for the development and progression of several neurological diseases. Likewise, astrocytic reactivity-a wellknown process that markedly influences the tissue remodeling after a central nervous system injury-is crucial for tissue remodeling after spinal cord injury（SCI）. However, the linkage between the above-mentioned mechanisms after SCI remains poorly understood. We sought to investigate the relation between both glial fibrillary acidic protein（GFAP） and S100 calcium-binding protein B（S100B）（astrocytic reactivity classical markers） and global histone H4 acetylation levels. Sixty-one male Wistar rats（aged ~3 months） were divided into the following groups： sham; 6 hours post-SCI; 24 hours post-SCI; 48 hours post-SCI; 72 hours post-SCI; and 7 days post-SCI. The results suggested that GFAP, but not S100B was associated with global histone H4 acetylation levels. Moreover, global histone H4 acetylation levels exhibited a complex pattern after SCI, encompassing at least three clearly defined phases（first phase： no changes in the 6, 24 and 48 hours post-SCI groups; second phase： increased levels in the 72 hours post-SCI group; and a third phase： return to levels similar to control in the 7 days post-SCI group）. Overall, these findings suggest global H4 acetylation levels exhibit distinct patterns of expression during the first week post-SCI, which may be associated with GFAP levels in the perilesional tissue. Current data encourage studies using H4 acetylation as a possible biomarker for tissue remodeling after spinal cord injury.

Ursolic acid induces neural regeneration after sciatic nerve injury

In this study, we aimed to explore the role of ursolic acid in the neural regeneration of the injured sciatic nerve. BALB/c mice were used to establish models of sciatic nerve injury through unilateral sciatic nerve complete transection and microscopic anastomosis at 0.5 cm below the ischial tuber-osity. The successful y generated model mice were treated with 10, 5, or 2.5 mg/kg ursolic acid via intraperitoneal injection. Enzyme-linked immunosorbent assay results showed that serum S100 protein expression level gradual y increased at 1-4 weeks after sciatic nerve injury, and significantly decreased at 8 weeks. As such, ursolic acid has the capacity to significantly increase S100 protein expression levels. Real-time quantitative PCR showed that S100 mRNA expression in the L 4-6 segments on the injury side was increased after ursolic acid treatment. In addition, the muscular mass index in the soleus muscle was also increased in mice treated with ursolic acid. Toluidine blue staining revealed that the quantity and average diameter of myelinated nerve fibers in the injured sciatic nerve were significantly increased after treatment with ursolic acid. 10 and 5 mg/kg of ursolic acid produced stronger effects than 2.5 mg/kg of ursolic acid. Our findings indicate that ursolic acid can dose-dependently increase S100 expression and promote neural regeneration in BALB/c mice fol owing sciatic nerve injury.