高压氧预处理对兔脊髓缺血再灌注损伤的保护机制探讨

目的:探讨高压氧预处理对免脊髓缺血再灌注损伤的保护机制.方法:20只雄性新西兰大白兔,随机分为2组(每组n=10):对照组为常压空气组;HBO组为高压氧预处理组.采用肾下腹主动脉阻断法造成脊髓缺血再灌注损伤,观察两组再灌注后4h、12h、24h、48h时的神经功能评分;再灌注48 h时取出腰段脊髓组织(L5-7)测定脊髓抗氧化酶活性(SOD、CAT及GSH-px)及MAD含量.结果:再灌注4h、12h、24h、48h时,HBO组神经功能学评分均明显优于对照组(P<0.05).再灌注48h时,HBO组脊髓匀浆SOD、CAT及GSH-px活性明显高于对照组(P<0.05),脊髓匀浆MDA含量明显低于对照组(P<0.05).相关性分析发现,再灌注48 h时后肢运动神经功能学评分与脊髓SOD、CAT及GSH-px活性呈正相关(r=0.82,0.65,0.54,P<0.05),与脊髓MDA含量呈负相关(r=-0.69,P<0.05).结论:高压氧预处理对脊髓缺血再灌注损伤的保护机制可能与上调内源性抗氧化酶活性和清除自由基有关.     

高压氧对大鼠脊髓损伤后局部炎症因子的影响

目的:观测高压氧对脊髓损伤大鼠运动功能恢复的作用及机制研究。方法:采用改良Allen’S法制作大鼠不完全脊髓损伤模型。45只SD大鼠,随机分为3组(n=15):假手术组,脊髓损伤对照组和高压氧治疗组。分别于治疗后1、2、3及4周,利用BBB评分法对大鼠进行运动功能评分。应用ELISA法测定手术后14 d大鼠损伤脊髓组织中肿瘤坏死因子(TNF-α)、白介素-6(IL-6)、γ干扰素(IFN-γ)的含量。结果:成功建立大鼠不完全性脊髓损伤模型,运动功能评分显示高压氧治疗组和模型组差异显著。ELISA结果显示脊髓损伤后脊髓组织中炎症因子含量显著升高,而高压氧处理后,炎症因子含量明显降低。结论:高压氧可通过降低损伤脊髓局部的炎症反应,达到改善脊髓损伤的作用。     

Pregnancy following spinal cord injury.

Each year about 2,000 women of childbearing age in the United States have a spinal cord injury. Only a few mostly anecdotal reports describe pregnancy after such an injury. In a retrospective study of 16 women with a spinal cord injury, half of whom have a complete injury and about half quadriplegia, 25 pregnancies occurred, with 21 carried to full term. The women delayed pregnancy an average of 6.5 years after their injury, with an average age at first pregnancy of 26.8 years. Cesarean section was necessary in 4 patients because of inadequate progress of labor. In 5 deliveries an episiotomy and local anesthesia were required, 7 required epidural anesthesia, including all cesarean sections, and 10 did not require anesthesia. Several complications have been identified in the antepartum, intrapartum, and postpartum periods including autonomic hyperreflexia, premature labor, pressure sores, urinary tract infections, abnormal presentation, and failure to progress. Ultrasonography and amniocentesis were used selectively. Women with spinal cord injuries can have healthy children, although there are significant risks and these women have special needs.     

Regulation of clusterin expression following spinal cord injury

We have investigated the localization and regulation of a putative extracellular chaperone, clusterin, in the rat spinal cord after lesion. In control animals, clusterin is expressed in motoneurons, in meningeal and ependymal cells, and in astrocytes mainly located beneath the pial surface. Beginning at day 2 after hemisection at segmental level C6, clusterin levels increase in GFAP-positive astrocytes within the lesioned segment. Three weeks after trauma, clusterin mRNA and protein are elevated in neurons close to the lesion site and in glial elements within scar tissue and within degenerating fiber tracts rostral and caudal to the lesion. This study provides evidence for a role of clusterin in the subacute and late phase of spinal cord injury.     

Glial and axonal regeneration following spinal cord injury

Spinal cord injury (SCI) has been regarded clinically as an irreversible damage caused by tissue contusion due to a blunt external force. Past research had focused on the analysis of the pathogenesis of secondary injury that extends from the injury epicenter to the periphery, as well as tissue damage and neural cell death associated with secondary injury. Recent studies, however, have proven that neural stem (progenitor) cells are also present in the brain and spinal cord of adult mammals including humans. Analyses using spinal cord injury models have also demonstrated active dynamics of cells expressing several stem cell markers, and methods aiming at functional reconstruction by promoting the potential self-regeneration capacity of the spinal cord are being explored. Furthermore, reconstruction of the neural circuit requires not only replenishment or regeneration of neural cells but also regeneration of axons. Analysis of the tissue microenvironment after spinal cord injury and research aiming to remove axonal regeneration inhibitors have also made progress. SCI is one of the simplest central nervous injuries, but its pathogenesis is associated with diverse factors, and further studies are required to elucidate these complex interactions in order to achieve spinal cord regeneration and functional reconstruction.Key words: glia, regeneration, spinal cord, injury, axon     

Glial and axonal regeneration following spinal cord injury

Spinal cord injury (SCI) has been regarded clinically as an irreversible damage caused by tissue contusion due to a blunt external force. Past research had focused on the analysis of the pathogenesis of secondary injury that extends from the injury epicenter to the periphery, as well as tissue damage and neural cell death associated with secondary injury. Recent studies, however, have proven that neural stem (progenitor) cells are also present in the brain and spinal cord of adult mammals including humans. Analyses using spinal cord injury models have also demonstrated active dynamics of cells expressing several stem cell markers, and methods aiming at functional reconstruction by promoting the potential self-regeneration capacity of the spinal cord are being explored. Furthermore, reconstruction of the neural circuit requires not only replenishment or regeneration of neural cells but also regeneration of axons. Analysis of the tissue microenvironment after spinal cord injury and research aiming to remove axonal regeneration inhibitors have also made progress. SCI is one of the simplest central nervous injuries, but its pathogenesis is associated with diverse factors, and further studies are required to elucidate these complex interactions in order to achieve spinal cord regeneration and functional reconstruction.     

The influence of the adrenal glands upon acute spinal cord injury

The contribution of the adrenal glands to the pressor and nerve tissue necrotic responses that follow acute paralyzing spinal cord injury was determined in cats by total adrenal gland removal. The study suggests that either epinephrine or endogenous steroids may exert posttraumatic protective influences on the cord since after adrenalectomy, both the systematic pressor response and local hemorrhagic necrosis are significantly increased.     

The effect of hyperbaric oxygen treatment on oxidative stress in experimental acute necrotizing pancreatitis

Various protocols may be used for acute pancreatitis treatment. Recently, the benefit of hyperbaric oxygen (HBO) has been demonstrated. To clarify the mechanism of HBO on the process of the acute pancreatitis, we determined the levels of antioxidant enzymes in an acute pancreatitis model. Forty-five Sprague-Dawley rats were randomly divided into three groups: Group I: sham group (n=15), Group II: pancreatitis group (n=15), Group III: pancreatitis group undergoing HBO therapy (n=15). HBO was applied postoperatively for 5 days, two sessions per day at 2.5 fold absolute atmospheric pressure (ATA) for 90 min. Superoxide dismutase (Cu/Zn-SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH Px) activity were measured in pancreatic tissue and erythrocyte lysate. MDA and GSH Px were also determined in plasma. In addition, amylase levels were measured in the serum. While serum amylase levels and MDA values in erythrocyte, plasma and pancreatic tissue were decreased, the levels of GSH Px and SOD were found to be significantly increased in the Group III as compared to those of the Group II. The findings of our study suggest that HBO has beneficial effects on the course of acute pancreatitis and this effect may occur through the antioxidant systems.     

Effect of Nrf2 signaling pathway on the improvement of intestinal epithelial barrier dysfunction by hyperbaric oxygen treatment after spinal cord injury

Disruption of the intestinal epithelial barrier following spinal cord injury (SCI) seriously affect long-term quality of life. Oxidative stress-induced epithelial cells’ injury contributes to the epithelial barrier dysfunction. Hyperbaric oxygen (HBO) treatment has been proved to alleviate SCI. However, it is unclear whether or not HBO treatment affects intestinal barrier function following SCI. In this study, our purpose was to explore the impact of HBO treatment on intestinal epithelial barrier function and underlying mechanisms following SCI. An SCI model was established in rats, and the rats received HBO treatment. Intestinal injury, mucosal permeability, intercellular junction proteins, and oxidative stress indicators were evaluated in our study. We found that HBO treatment significantly alleviated intestinal histological damage, reduced mucosal permeability, and markedly prevented bacterial translocation. Furthermore, HBO treatment significantly increased the expression of Claudin-1 and E-cadherin, inhibited intestinal tissue oxidative stress as demonstrated by upregulation of superoxide dismutase and glutathione, and HBO downregulated malondialdehyde. Mechanically, we demonstrated that HBO treatment ameliorated intestinal oxidative stress possibly through upregulating nuclear factor E2-related factor 2 (Nrf2) and its downstream targets, Heme oxygenase-1(HO-1), NADH-quinone oxidoreductase-1(NQO-1), and glutamate cysteine ligase catalytic subunit (GCLC). These results suggested that HBO treatment triggered antioxidative effects against intestinal epithelial barrier dysfunction by promoting Nrf2 signaling pathway after SCI.     

The effect of hyperbaric oxygen treatment on aspiration pneumonia

We have studied whether hyperbaric oxygen (HBO) prevents different pulmonary aspiration materials-induced lung injury in rats. The experiments were designed in 60 Sprague-Dawley rats, ranging in weight from 250 to 300 g, randomly allotted into one of six groups (n = 10): saline control, Biosorb Energy Plus (BIO), hydrochloric acid (HCl), saline + HBO treated, BIO + HBO treated, and HCl + HBO treated. Saline, BIO, HCl were injected into the lungs in a volume of 2 ml/kg. A total of seven HBO sessions were performed at 2,4 atm 100% oxygen for 90 min at 6-h intervals. Seven days later, rats were sacrificed, and both lungs in all groups were examined biochemically and histopathologically. Our findings show that HBO inhibits the inflammatory response reducing significantly (P < 0.05) peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar edema, alveolar exudate, alveolar histiocytes, interstitial fibrosis, granuloma, and necrosis formation in different pulmonary aspiration models. Pulmonar aspiration significantly increased the tissue HP content, malondialdehyde (MDA) levels and decreased (P < 0.05) the antioxidant enzyme (SOD, GSH-Px) activities. HBO treatment significantly (P < 0.05) decreased the elevated tissue HP content, and MDA levels and prevented inhibition of SOD, and GSH-Px (P < 0.05) enzymes in the tissues. Furthermore, there is a significant reduction in the activity of inducible nitric oxide synthase, TUNEL and arise in the expression of surfactant protein D in lung tissue of different pulmonary aspiration models with HBO therapy. It was concluded that HBO treatment might be beneficial in lung injury, therefore, shows potential for clinical use.     

Impacts of epidural electrical stimulation on Wnt signaling,FAAH, and BDNF following thoracic spinal cord injury in rat

Electrical stimulation (ES) has been shown to improve some of impairments after spinal cord injury (SCI), but the underlying mechanisms remain unclear. The Wnt signaling pathways and the endocannabinoid system appear to be modulated in response to SCI. This study aimed to investigate the effect of ES therapy on the activity of canonical/noncanonical Wnt signaling pathways, brain-derived neurotrophic factor (BDNF), and fatty-acid amide hydrolase (FAAH), which regulate endocannabinoids levels. Forty male Wistar rats were randomly divided into four groups: (a) Sham, (b) laminectomy + epidural subthreshold ES, (c) SCI, and (d) SCI + epidural subthreshold ES. A moderate contusion SCI was performed at the thoracic level (T10). Epidural subthreshold ES was delivered to upper the level of T10 segment every day (1 hr/rat) for 2 weeks. Then, animals were killed and immunoblotting was used to assess spinal cord parameters. Results revealed that ES intervention for 14 days could significantly increase wingless-type3 (Wnt3), Wnt7, β-catenin, Nestin, and cyclin D1 levels, as well as phosphorylation of glycogen synthase kinase 3β and Jun N-terminal kinase. Additionally, SCI reduced BDNF and FAAH levels, and ES increased BDNF and FAAH levels in the injury site. We propose that ES therapy may improve some of impairments after SCI through Wnt signaling pathways. Outcomes also suggest that BDNF and FAAH are important players in the beneficial impacts of ES therapy. However, the precise mechanism of BDNF, FAAH, and Wnt signaling pathways on SCI requires further investigation.     

Effects of magnesium sulphate following spinal cord injury in rats

Neutrophil infiltration has been implicated in the secondary destructive pathomechanisms after initial mechanical injury to the spinal cord. Tissue myeloperoxidase (MPO) activity has been shown to be an exclusive indicator of the extent of post-traumatic neutrophil infiltration. We have studied the effect of magnesium sulphate on MPO activity after spinal cord injury in rats. Rats were randomly allocated into 5 groups. Group 1 was control and normal spinal cord samples were obtained after clinical examination. Forty g-cm contusion injury was introduced to Group 2. Group 3 was vehicle, 1 ml of physiological saline was injected post-trauma. Group 4 was given 30 mg/kg methylprednisolone sodium succinate (MPSS) immediately after trauma. Group 5 was given 600 mg/kg magnesium sulphate immediately after trauma. Animals were examined by inclined plane technique of Rivlin and Tator 24 h after trauma. Spinal cord samples obtained following clinical evaluations. Magnesium sulphate treatment improved early functional scores and decreased MPO activity. These findings revealed that magnesium sulphate treatment possesses neuroprotection on early clinical results and on neutrophil infiltration after acute contusion injury to the rat spinal cord.     

Cellular-scale transport in deformed skeletal muscle following spinal cord injury

Deep tissue injury (DTI) is a severe pressure ulcer initiating in weight-bearing skeletal muscles. Being common in spinal cord injury (SCI) patients, DTI is associated with mechanical cell damage and ischaemia. Muscle microanatomy in SCI patients is characterised by reduced myofibre sizes and smaller, fewer capillaries. We hypothesise that these changes influence mass transport in SCI muscles, making DTI more probable. Using multiphysics models of microscopic cross-sections through normal and SCI muscles, we studied effects of the following factors on transport of glucose and myoglobin (potential biomarker for early DTI detection): (i) abnormal SCI muscle microanatomy, (ii) large tissue deformations and (iii) ischaemia. We found that the build-up of concentrations of glucose and myoglobin is slower for SCI muscles, which could be explained by the pathological SCI microanatomy. These findings overall suggest that microanatomical changes in muscles post-SCI play an important role in the vulnerability of the SCI patients to DTI.