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Chinese Neurosurgical Journal 2021年第2期7卷 131-136页

作者： Hui Ma Lian Xu Cui Ping Kuen Lam Cindy S.W.Tong Kin K.Y.Lo George K.C.Wong Wai Sang Poon Division of Neurosurgery Chow Tai Fook-Cheng Yu Tung Surgical Stem Cell Research CenterDepartment of SurgeryThe Chinese University of Hong KongShatinHong KongSARChina Division of Neurosurgery Department of SurgeryFo Shan First People’s HospitalFoshanGuangdongChina

Background:Our previous studies showed that topical application of mesenchymal stem cells(MSCs)improved functional recovery in rat traumatic brain injury(TBI)model,and hypoxic precondition further enhanced the therapeutic effects of MSCs.There was no previous study on the attenuation of Cerebral edema by MSCs.We investigated whether topical application of normoxic and hypoxic MSCs could reduce Cerebral edema in an experimental TBI model.Methods:Two million normoxic(N=24)and hypoxic(N=24)MSCs were applied topically to exposed the cerebral cortex in a controlled cortical impact(CCI)model.The MSCs were fixed in position with fibrin glue.No treatment was given to control animals(TBI only:n=24).After surgery,four animals in each group were sacrificed daily(day 1 to day 6)for edema evaluation.Normal animals without TBI were used as reference(n=4).The expressions of GFAP,AQP4,and MMP9 were also investigated by immunofluorescence staining and RT-PCR at day 3.Results:The edema peaked within 3 days after TBI.Compared with the control,hypoxic MSCs reduced brain water content significantly(pedema formation.

关键词： Topical MSCs Cerebral edema TBI

Telmisartan Reduced Cerebral edema by Inhibiting NLRP_3 Inflammasome in Mice with Cold Brain Injury

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2016年第4期36卷 576-583页

作者：魏欣胡晨晨张亚丽姚尚龙毛卫克 Department of Anesthesiology Union Hospital Tongji Medical College Huazhong University of Science and Technology

The aim of this study was to investigate the possible beneficial role of telmisartan in Cerebral edema after traumatic brain injury（TBI） and the potential mechanisms related to the nucleotide-binding oligomerization domain（NOD）-like receptor（NLR） pyrin domain-containing 3（NLRP3） inflammasome activation. TBI model was established by cold-induced brain injury. Male C57BL/6 mice were randomly assigned into 3, 6, 12, 24, 48 and 72 h survival groups to investigate Cerebral edema development with time and received 0, 5, 10, 20 and 40 mg/kg telmisartan by oral gavage, 1 h prior to TBI to determine the efficient anti-edemic dose. The therapeutic window was identified by post-treating 30 min, 1 h, 2 h and 4 h after TBI. Blood-brain barrier（BBB） integrity, the neurological function and histological injury were assessed, at the same time, the m RNA and protein expression levels of NLRP3 inflammasome, IL-1β and IL-18 concentrations in peri-contused brain tissue were measured 24 h post TBI. The results showed that the traumatic Cerebral edema occurred from 6 h, reached the peak at 24 h and recovered to the baseline 72 h after TBI. A single oral dose of 5, 10 and 20 mg/kg telmisartan could reduce Cerebral edema. Post-treatment up to 2 h effectively limited the edema development. Furthermore, prophylactic administration of telmisartan markedly inhibited BBB impairment, NLRP3, apoptotic speck-containing protein（ASC） and Caspase-1 activation, as well as IL-1β and IL-18 maturation, subsequently improved the neurological outcomes. In conclusion, telmisartan can reduce traumatic Cerebral edema by inhibiting the NLRP3 inflammasome-regulated IL-1β and IL-18 accumulation.

关键词： telmisartan traumatic brain injury Cerebral edema NLRP3 inflammasome inflammation

Risk factors and predictive model of Cerebral edema after road traffic accidents-related traumatic brain injury

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Chinese Journal of Traumatology - English Edition 2024年第3期27卷 153-162页

作者： Chen D.-Y. Wu P.-F. Zhu X.-Y. Zhao W.-B. Shao S.-F. Xie J.-R. Yuan D.-F. Zhang L. Li K. Wang S.-N. Zhao H. Institute for Traffic Medicine Daping Hospital Army Medical University Chongqing 400042 China Department of Radiology Daping Hospital Army Medical University Chongqing 400042 China Chongqing Key Laboratory of Traffic Injury and Vehicle Ergonomics Chongqing 400042 China Wound Trauma Medical Center State Key Laboratory of Trauma Burns and Combined Injury Institute of Surgery Research Daping Hospital Army Medical University Chongqing 400042 China

Purpose: Cerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries. Methods: This case-control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median (Q1, Q3). Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve. Results: According to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% confidence interval (CI): 2.08 − 25.42, p = 0.002), 2.85 (95% CI: 1.11 − 7.31, p = 0.030), 2.62 (95% CI: 1.12 − 6.13, p = 0.027), 2.44 (95% CI: 1.25 − 4.76, p = 0.009), and 1.5 (95% CI: 1.10 − 2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ2 = 13.82, adjusted R2 = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ2 = 18.48, adjusted R2 = 0.54). Finally, we conducted a receiver operator characteristic curve analys

关键词： Cerebral edema Risk factors Road traffic accident Time window Traumatic brain injury

Effects of low-dose dexamethasone on Cerebral edema in rats with traumatic brain injury complicated by seawater drowning

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Chinese Journal of Nautical Medicine and Hyperbaric Medicine 2024年第2期31卷 159-162and168页

作者： Zeng Z. Zhang H. Wang S. Wei L. Department of Neurosurgery Fuzong Clinical Medical College of Fujian Medical University No. 900 Hospital of PLA Fuzhou 350025 China

Objective To observe the effects of dexamethasone（DX）on Cerebral edema in rats with traumatic brain injury（TBI）complicated by seawater drowning（SWD）. Methods SD rats were randomly divided into sham group，TBI+SWD group，and DX treatment group，according to the random number table method.. TBI+SWD composite model was used. The rats in the DX treatment group were intraperitoneally injected with 1 mL DX（1 mg/kg）. The modified neurological severity score（mNSS）and brain water content were detected. The pathological changes of hippocampus were observed by HE staining，and the expression of aquaporin 4（AQP4）in hippocampus was observed by immunohistochemical staining.Results Compared with the sham group，the mNSS scores and brain water content of the TBI+SWD group and the DX treatment group were significantly increased （P0.05）. Compared with the TBI+SWD group，the DX treatment group had significant improvements in neuronal nuclear pyknosis，cell swelling，and tissue matrix laxity after injury. AQP4 positive expression was observed in the hippocampus of rats in the TBI+SWD group and the DX treatment group at each time point after injury.Conclusion Low-dose DX can improve the brain edema of the rats with trauma brain injury complicated by seawater drowning，but the brain protection effect may be limited. © 2024 Chinese Medical Journals Publishing House Co.Ltd. All rights reserved.

关键词： Aquaporin Cerebral edema Dexamethasone Seawater drowning Traumatic brain injury

Aquaporin-4 in the formation of Cerebral edema following severe burns What role do arginine vasopressin levels play?

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Neural Regeneration Research 2010年第7期5卷 531-537页

作者： Shifang Luo Department of Anatomy Chongqing Medical University Chongqing 400016 China Research Center of Neuroscience Chongqing Medical University Chongqing 400016 China

BACKGROUND： Aquaporin-4 （AQP-4）, which is able to rapidly transport water within the brain, is highly expressed in brain tissue. It also plays an important role in the formation of Cerebral edema following brain injury. However, the role of AQP-4 in the formation of Cerebral edema following severe bums remains unknown. OBJECTIVE： To study changes in AQP-4 protein and mRNA expression during formation of Cerebral edema following severe burns, and to explore the correlation between AQP-4 protein and mRNA expression with plasma levels of arginine vasopressin （AVP）. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Research Center of Neuroscience, Chongqing Medical University from 2007 to 2008. MATERIALS： Biotin-labeled goat anti-rabbit antibody was provided by Beijing Zhongshan Biotechnology, China; in situ hybridization kit was provided by Wuhan Boster Biotechnology, China; rabbit anti-AQP-4 polyclonal antibody and horseradish peroxidase-labeled goat anti-rabbit IgG were provided by Chemicon, USA; AVP radioimmunoassay kit was provided by the Research Department of Neurobiology, the Second Military Medical University of Shanghai, China. METHODS： A total of 180 adult, healthy, Wistar rats were randomly assigned to control and burn groups with 30 rats in each group. The burn group was observed at five different time points： 2, 6, 12, 24, and 48 hours after burn. Hair on the mouse back was removed to expose skin on the back. After 1 day, skin with the hair removed was dipped into 100℃ water for 15 seconds to induce grade III bum injury that measures 30% of total bum surface area. MAIN OUTCOME MEASURES： Brain water content was measured using the dry-wet weight method. AQP-4 protein and mRNA expressions were detected using immunohistochemistry, in situ hybridization, Western blot, and reverse transcription-polymerase chain reaction; dynamic changes in plasma AVP were detected using radioimmunoassay. RESULTS： Brain water content gradually increased following severe burn injury. AQP-

关键词： burn injury Cerebral edema aquaporin-4 aquaporin-4 mRNA arginine vasopressin brain injury

Effect of ischemic postconditioning on Cerebral edema and the AQP4 expression following hypoxic-eschemic brain damage in neonatal rats

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World Journal of Pediatrics 2015年第2期11卷 165-170页

作者： Ling Yu Shu-Juan Fan Li Liu Mi Xiao Xiao-Jie Lin Yong Liu Hai-Xia Lv Xin-Lin Chen Jian-Xin Liu Department of Neonatology First Affiliated HospitalXi'an Jiaotong University School of MedicineXi'anChina Department of Nephrology Children's HospitalZhejiang University School of MedicineChina Institute of Neurobiology of Xi'an Jiaotong University School of Medicine Xi'anChina

Background:A rat model for neonatal hypoxic-ischemic brain damage(HIBD)was established to observe the effect of ischemic postconditioning(IPostC)on Cerebral edema and the AQP4 expression following HIBD and to verily the neuroprotection of IPostC and the relationship between changes of AQP4 expression and Cerebral edema.Methods:Water content was measured with dry-wet method,and AQP4 transcription and the protein expression of the lesions were detected with real-time PCR and immunohistochemistry staining,respectively.Results:Within 6-48 hours,the degree of ipsilateral Cerebral edema was significantly lower in IPostC-15 s/15 s group than in HIBD group.Similar to the HIBD group,the AQP4 transcription and expression in the IPostC group showed a downward and then upward trend.But the expression was still more evident in the HIBD group than in the IPostC-15 s/15 s group.From 24 to 48 hours,IPostC-15 s/15 s decreased the slowing down expression of AQP4.Conclusion:IPostC has neuroprotective effect on neonatal rats with HIBD and it may relieve Cerebral edema by regulating the expression of AQP4.

关键词： AQP4 Cerebral edema hypoxic-ischemic brain injury ischemic postconditioning neonate

The ameliorative effect of bloodletting puncture at hand twelve Jing-Well points on Cerebral edema induced by permanent middle cerebral ischemia via protecting the tight junctions of the blood-brain barrier

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The ameliorative effect of bloodletting puncture at hand twe...

Over hydration in diabetic ketoacidosis may increase the risk of Cerebral edema in children

中国神经科学学会第十二届全国学术会议

作者： Qiu-Mei ZHU Nan-Nan YU Zhen-Guo WANG Jun-Tao YANG Yi GUO Ze-Lin CHEN Zhi-Fang XU Acupuncture Research Center Tianjin University of Traditional Chinese Medicine Department of Traditional Chinese Medicine Xijing Hospital The Fourth Military Medical University Xi'an Encephalopathy Hospital of Traditional Chinese Medicine Acu-moxibustion and Tuina Department Tianjin University of Traditional Chinese Medicine

Objective: A major and severe complication of ischemic stroke is Cerebral edema, which exacerbates the brain injury and promotes clinical deterioration. Our previous studies have demonstrated that bloodletting puncture at hand twelve Jing-well points（HTWP） could improve the conscious disturbance and reduce Cerebral edema in ischemic stroke patients and rats. The present study was designed to examine whether bloodletting puncture at HTWP protects against blood-brain barrier（BBB） disruption and the underlying mechanism by using permanent middle cerebral artery occlusion（pMCAO） rat model. Methods: Rats were subjected to pMCAO and treated with bloodletting puncture at HTWP once daily. Brain edema was measured according to the wet and dry weight method, and the Evans blue extravasation and electron microscopy were used to evaluate the integrity of the BBB. RT-qPCR was carried out to analyze the expression of occludin, claudin-5, ICAM-1, VEGF. Results: The results revealed that bloodletting puncture treatment reduced the water content and the BBB permeability following ischemic stroke. The ameliorated tight junctions were observed under electron microscopy in bloodletting puncture group. Further study demonstrated that the expression of occludin and claudin-5 were up-regulated, while ICAM-1 and VEGF were down-regulated by bloodletting puncture compared with those in pMCAO group. Conclusion: Bloodletting puncture at HTWP alleviated ischemic stroke-induced Cerebral edema via protecting the tight junctions of BBB, offering a novel medication for acute ischemic stroke.

关键词： Cerebral edema blood-brain barrier bloodletting puncture at hand twelve Jing-well points tight junction permanent middle cerebral artery occlusion

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新疆医科大学学报 2013年第6期36卷 839-844页

作者： Zakaullh Khan Dulikun Muzhapaer Department of Pediatric The First Affiliated Hospital of Xinjiang Medical University

Objectives Over-hydration in diabetic ketoacidosis(DKA) may increase the risk of Cerebral edema in children.Methods We have organized a prospective descriptive cohort study of 38pediatric patients aged 1month to 14years,who were diagnosed with DKA with 41episodes of diabetic ketoacidosis,presented to the pediatric emergency department at the First Affiliated Hospital of Xinjiang Medical University from January 2010to February 2012.This study was approved by the Ethics Committee of The First Affiliated Hospital of Xinjiang Medical University.Results The magnitude presentation of the percentile 25%-70% was in the ratio of 5.6%(3.4%-8.2%)(6.1±4).So there was no clinical and biochemical assessment variation needed.These both of the variations,all of the diabetic ketoacidosis patient approached.Further all the patient variations were not correlated with the amplitude of variation and magnitude presentation and did not affect the fluid concentration and the quantity of the fluid was 47.8mL / kg(36.556.3) in the first 12hours.Conclusion For the conclusion of the exact parameters and the magnitude variations of the fluid in the patients of diabetic ketoacidosis,all of the conformations need study on the larger scale.

关键词： diabetic ketoacidosis(DKA) Cerebral edema pediatric patients

Effect of Glycerol Fructose Combined with Mannitol on Patients with cerebral Hemorrhage and Cerebral edema

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Journal of Clinical and Nursing Research 2022年第1期6卷 1-3页

作者： Xuexinyu Ma Jianbo Wang Shaanxi University of Chinese Medicine Xianyang 712046China Sichuan Academy of Chinese Medical Sciences Chengdu 610041China

Objective:To observe the effect of glycerol fructose combined with mannitol in the treatment of patients with clinical intracerebral hemorrhage complicated by Cerebral edema and increased intracranial pressure,and to evaluate the clinical application value of this treatment.Methods:Seventy patients with cerebral hemorrhage complicated by brain edema were randomly divided into observation and control groups.Both groups had exactly the same number of study participants.There were some differences in specific treatment methods.The specific process is as follows:The control group was treated with mannitol,while the observation group was treated with dual-purpose glycerol fructose.Several important indicators after treatment in the two groups were scored,the effects between different groups were compared,and the effect of clinical treatment was evaluated.Results:The final effect was compared and analyzed.After data analysis,we found that the intracranial pressure of the observation group was lower,the volume of brain edema was significantly reduced(Pedema.

关键词： cerebral hemorrhage Cerebral edema Clinical treatment Glycerol fructose Mannitol Combination medication

Mannitol inhibits the proliferation of neural stem cell by a p38 mitogen-activated protein kinase-dependent signaling pathway

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Chinese Journal of Traumatology 2024年第1期27卷 42-52页

作者： Hai-Zhen Duan Xin Zhou Quan Hu Meng-Long Liu Shu-Hong Wang Ji Zhang Xu-Heng Jiang Tian-Xi Zhang An-Yong Yu Department of Emergency Affiliated Hospital of Zunyi Medical UniversityZunyi563000Guizhou provinceChina Dazhou Vocational College of Chinese Medicine Dazhou635000Sichuan provinceChina Dachuan District Traditional Chinese Medicine Hospital Dazhou635000Sichuan provinceChina

Purpose:Mannitol is one of the first-line drugs for reducing Cerebral edema through increasing the extracellular osmotic pressure.However,long-term administration of mannitol in the treatment of Cerebral edema triggers damage to neurons and astrocytes.Given that neural stem cell(NSC)is a subpopulation of main regenerative cells in the central nervous system after injury,the effect of mannitol on NSC is still elusive.The present study aims to elucidate the role of mannitol in NSC proliferation.Methods:C57 mice were derived from the animal house of Zunyi Medical University.A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation.Initially,mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining.In order to investigate the impact of mannitol on NSC proliferation,both cell counting kit-8 assays and neurospheres formation assays were conducted.Thein vitro effects of mannitol were examined at various doses and time points.In order to elucidate the role of Aquaporin 4(AQP4)in the suppressive effect of mannitol on NSC proliferation,various assays including reverse transcription polymerase chain reaction,western blotting,and immunocytochemistry were conducted on control and mannitol-treated groups.Additionally,the phosphorylated p38(p-p38)was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation.Finally,to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent(MAPK)signaling pathway in the observed inhibition of NSC proliferation by mannitol,SB203580 was employed.All data were analyzed using SPSS 20.0 software(SPSS,Inc.,Chicago,IL).The statistical analysis among multiple comparisons was performed using one-way analysis of variance(ANOVA),followed by Turkey’’s post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test.Comparisons between 2 groups were determined using Student’s t-te

关键词： Mannitol Cerebral edema Neural stem cell Proliferation AQP4 p38 MAPK signaling pathway