BACKGROUND Early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-1(PEBEL1)is a rare autosomal recessive severe neurometabolic disease.The aim of this study was to investigate the clinical ...BACKGROUND Early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-1(PEBEL1)is a rare autosomal recessive severe neurometabolic disease.The aim of this study was to investigate the clinical characteristics and genetic pathogenicity of PEBEL1 caused by rare NAXE(or APOA1BP)-related defects.CASE SUMMARY The patient was a girl aged 2 years and 10 mo.She was hospitalized due to walking disorder for>40 d.The clinical manifestations were ataxia,motor function regression,hypotonia,and eyelid ptosis.Within 1 mo of hospitalization,she developed sigh breathing,respiratory failure,cerebellar edema and brain hernia,and finally she died.Changes were found in cranial imaging,including cerebellar edema accompanied by symmetrical myelopathy.Through whole exome sequencing,we detected NAXE compound heterozygous variation(NM 144772.3)c.733A>C(p.Lys245Gln,dbSNP:rs770023429)and novel variation c.370G>T(p.Gly124Cys)in the germline gene.The clinical features and core phenotypes of this case were consistent with 18 previously reported cases of PEBEL1.CONCLUSION This is the first case of NAXE-related PEBEL1 with severe clinical phenotype in China' Mainland.The p.Gly124Cys mutation discovered in this case has enriched the pathogenic variation spectrum of NAXE.展开更多
BACKGROUND: Stereo-tactic radiation therapy (SRT) is widely used to treat intracranial diseases, but some patients suffered from radiation induced brain edema after SRT. Once radiation induced brain edema occurs, the ...BACKGROUND: Stereo-tactic radiation therapy (SRT) is widely used to treat intracranial diseases, but some patients suffered from radiation induced brain edema after SRT. Once radiation induced brain edema occurs, the treatment is quite difficult, and it always leads to a poor outcome. Dexamethasone has certain therapeutic effect on traumatic brain edema, but the biological mechanism is still unclear. OBJECTIVE: To observe the effect of dexamethasone on the neutrophil expression of CD18. DESIGN: A randomized control observation. SETTING: Changhai Hospital of the Second Military Medical University of Chinese PLA. MATERIALS: The experiment was carried out in Changhai Hospital of the Second Military Medical University of Chinese PLA from January 1999 to December 1999. Twenty SD rats (male and female each in half) weighing (250±50) g were used. METHODS: Twenty SD rats were divided into four groups at random. ① Blank control group (n=5): The rats were not treated without dexamethasone or irradiation; ② Irradiation group (n=5): The rats were given irradiation but no dexamethasone treatment; ③ Irradiation+1 mg/kg dexamethasone group (n=5): The rats were treated with irradiation and dexamethasone of 1 mg/kg; ④ Irradiation+5 mg/kg dexamethasone group (n=5): The rats were treated with irradiation and dexamethasone of 5 mg/kg. The heads of the rats were irradiated with 10 MeV X-ray (30 Gy), and brain tissue was removed after 2 weeks to observe the pathological changes. Blood samples were taken from the carotid artery, gradient centrifugation was used, and neutrophile layer was obtained, the level of neutrophile expression of CD18 mRNA and quantity of membrane proteins in blood were detected with Northern blot and flow cytometry respectively. MAIN OUTCOME MEASURES: ① Blood cell count; ② Pathological results; ③ level of neutrophile expression of CD18 mRNA and quantity of membrane proteins. RESULTS: All the 20 SD rats were involved in the analysis of results without deletion. At 2 weeks after irradiation, obvious cell injury could be observed under light microscope. The level of neutrophile expression of CD18 mRNA and quantity of membrane proteins in blood were obviously increased, but the severity of cell injury was relieved in the irradiation+1 and 5 mg/kg dexamethasone groups, and the CD18 expression was markedly suppressed (P < 0.05), and the suppression was more obvious in the irradiation+5 mg/kg dexamethasone group than in the irradiation+1 mg/kg dexamethasone group (P < 0.01). CONCLUSION: Dexamethasone can reduce the radiation induced brain edema by inhibiting the expression of CD18.展开更多
The aquaporin-4(AQP4)is a highly selective membrane protein.It is important for the body to maintain the water balance between internal and external environment of cells,the studies have found that the abnormal expres...The aquaporin-4(AQP4)is a highly selective membrane protein.It is important for the body to maintain the water balance between internal and external environment of cells,the studies have found that the abnormal expression of AQP4 is related to the occurrence of many diseases.The cerebral edema is the most common and serious complication of brain trauma,and its pathogenesis is closely related to AQP4.The development of multimodal magnetic resonance imaging(M-MRI)could been provided imaging basis for accurate diagnosis of traumatic brain edema.In recent years,the correlation between AQP4 and M-MRI has become a hotspot of research.This paper reviews the research progress on the correlation between AQP4 expression in traumatic cerebral edema and M-MRI.展开更多
Objective: To determine whether VEGF plays a role in the development of peritumoral brain edema. Methods 50 meningioma patients and their VEGF expression were studied. We took a monoclonal antibody from mouse to VEGF ...Objective: To determine whether VEGF plays a role in the development of peritumoral brain edema. Methods 50 meningioma patients and their VEGF expression were studied. We took a monoclonal antibody from mouse to VEGF to stain the tumor cells, the vascular endothelial cells and the interstitial cells. The severity of brain edema was evaluated according to CT or MR scans by the following equation: edema index= V tumor +edema /Vtumor. The relationship between VEGF expression and edema index was analyzed statistically. Results VEGF was expressed in meningioma tumor cells, which is usually concentrated at the peripheral sites of the tumor. There was a positive linear correlation between the expression and the brain edema index. Conclusion VEGF may play a role in the development of peritumoral brain edema in meningioma patient.展开更多
Intracranial hypertension is a major cause of morbidity and mortality of patients suffering from fulminant hepatic failure. The etiology of this intracranial hypertension is not fully determined, and is probably multi...Intracranial hypertension is a major cause of morbidity and mortality of patients suffering from fulminant hepatic failure. The etiology of this intracranial hypertension is not fully determined, and is probably multifactorial, combining a cytotoxic brain edema due to the astrocytic accumulation of glutamine, and an increase in cerebral blood volume and cerebral blood flow, in part due to inflammation, to glutamine and to toxic products of the diseased liver. Validated methods to control intracranial hypertension in fulminant hepatic failure patients mainly include mannitol, hypertonic saline, indomethacin, thiopental, and hyperventilation. However all these measures are often not sufficient in absence of liver transplantation, the only curative treatment of intracranial hypertension in fulminant hepatic failure to date. Induced moderate hypothermia seems very promising in this setting, but has to be validated by a controlled, randomized study. Artificial liver support systems have been under investigation for many decades. The bioartificial liver, based on both detoxification and swine liver cells, has shown some efficacy on reduction of intracranial pressure but did not show survival benefit in a controlled, randomized study. The Molecular Adsorbents Recirculating System has shown some efficacy in decreasing intracranial pressure in an animal model of liver failure, but has still to be evaluated in a phase Ⅲ trial.展开更多
OBJECTIVE:To investigate the relationship of aquaporin 4(AQP4)and brain edema.DATA SOURCES:Using the terms of "aquaporin-4,brain edema",we searched PubMed database to identify studies published from January ...OBJECTIVE:To investigate the relationship of aquaporin 4(AQP4)and brain edema.DATA SOURCES:Using the terms of "aquaporin-4,brain edema",we searched PubMed database to identify studies published from January 1997 to April 2006 in the English languages.Meanwhile,we also searched China National Knowledge Infrastructure(CNKI)for related studies.STUDY SELECTION:The collected data were selected firstly.Studies on AQP4 and brain edema were chosen and their full-texts were searched for,and those with repetitive or review studies were excluded.DATA EXTRACTION:Totally 146 related studies were collected,42 of them were involved and the other 104 studies were used for reading reference data.DATA SYNTHESIS:AQP4 is a selective water permeable integral membrane protein.It is mainly expressed in astrocytes and ependymocyte,and is the important structural basis for water regulation and transportation between glial cells and cerebrospinal fluid or vessels.Phosphorylation is involved in the regulation of AQP4.AQP4 participates in the formation of brain edema caused by various factors.Studies on the structure and pathological changes of AQP4 are still in the initial stage,and the role and mechanism of AQP4 in the formation of brain edema is very unclear.CONCLUSION:AQP4 plays a critical regulating role in the formation of ischemic brain edema,but whether it is regulated by drugs lacks reliable evidence.展开更多
AIM:To compare rifaximin and insulin-like growth factor(IGF)-1 treatment of hyperammonemia and brain edema in cirrhotic rats with portal occlusion.METHODS:Rats with CCl4-induced cirrhosis with ascites plus portal vein...AIM:To compare rifaximin and insulin-like growth factor(IGF)-1 treatment of hyperammonemia and brain edema in cirrhotic rats with portal occlusion.METHODS:Rats with CCl4-induced cirrhosis with ascites plus portal vein occlusion and controls were randomized into six groups:Cirrhosis;Cirrhosis + IGF-1;Cirrhosis + rifaximin;Controls;Controls + IGF-1;and Controls + rifaximin.An oral glutamine-challenge test was performed,and plasma and cerebral ammonia,glucose,bilirubin,transaminases,endotoxemia,brain water content and ileocecal cultures were measured and liver histology was assessed.RESULTS:Rifaximin treatment significantly reduced bacterial overgrowth and endotoxemia compared with cirrhosis groups,and improved some liver function parameters(bilirubin,alanine aminotransferase and aspartate aminotransferase).These effects were associated with a significant reduction in cerebral water content.Blood and cerebral ammonia levels,and area-underthe-curve values for oral glutamine-challenge tests were similar in rifaximin-treated cirrhotic rats and control group animals.By contrast,IGF-1 administration failed to improve most alterations observed in cirrhosis.CONCLUSION:By reducing gut bacterial overgrowth,only rifaximin was capable of normalizing plasma and brain ammonia and thereby abolishing low-grade brain edema,alterations associated with hepatic encephalopathy.展开更多
AIM: To study the blood-brain barrier integrity, brain edema,animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication.METHODS: Adults male Wistar rats ...AIM: To study the blood-brain barrier integrity, brain edema,animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication.METHODS: Adults male Wistar rats were divided into four groups. Group I: sham operation; II: Prehepatic portal hypertension, produced by partial portal vein ligation; III:Acetaminophen intoxication and IV: Prehepatic portal hypertension plus acetaminophen. Acetaminophen was administered to produce acute hepatic injury. Portal pressure, liver serum enzymes and ammonia plasma levels were determined. Brain cortex water content was registered and trypan blue was utilized to study blood brain barrier integrity. Reflexes and behavioral tests were recorded.RESULTS: Portal hypertension was significantly elevated in groups II and IV. Liver enzymes and ammonia plasma levels were increased in groups II, III and IV. Prehepatic portal hypertension (group II), acetaminophen intoxication (group III) and both (group IV) had changes in the blood brain-barrier integrity (trypan blue) and hyperammonemia. Cortical edema was present in rats with acute hepatic injury in groups III and IV. Behavioral test (rota rod) was altered in group IV.CONCLUSION: These results suggest the possibility of another pathway for cortical edema production because blood brain barrier was altered (vasogenic) and hyperammonemia was registered (cytotoxic). Group IV, with behavioral altered test, can be considered as a model for study at an early stage of portal-systemic encephalopathy.展开更多
To investigate the role of AQP9 in brain edema, the expression of AQP9 in an infectious rat brain edema model induced by the injection of lipopolysaccharide (LPS) was examined. Immuno-histochemistry and reverse transc...To investigate the role of AQP9 in brain edema, the expression of AQP9 in an infectious rat brain edema model induced by the injection of lipopolysaccharide (LPS) was examined. Immuno-histochemistry and reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated that the expressions of AQP9 mRNA and protein at all observed intervals were significantly increased in LPS-treated animals in comparison with the control animals. Time-course analysis showed that the first signs of blood-brain barrier disruption and the increase of brain water content in LPS-treated animals were evident 6 h after LPS injection, with maximum value appearing at 12 h, which coincided with the expression profiles of AQP9 mRNA and protein in LPS-treated animals. The further correlation analysis revealed strong positive correlations among the brain water content, the disruption of the blood-brain barrier and the enhanced expressions of AQP9 mRNA and protein in LPS-treated animals. These results suggested that the regulation of AQP9 expression may play important roles in water movement and in brain metabolic homeostasis associated with the pathophysiology of brain edema induced by LPS injection.展开更多
The experimental model of traumatic brain injury was established in Sprague-Dawley rats according to Feeney’s free falling method.The brains were harvested at 2,6 and 24 hours,and at 3 and 5days after injury.Changes ...The experimental model of traumatic brain injury was established in Sprague-Dawley rats according to Feeney’s free falling method.The brains were harvested at 2,6 and 24 hours,and at 3 and 5days after injury.Changes in brain water content were determined using the wet and dry weights.Our results showed that water content of tissue significantly increased after traumatic brain injury,and reached minimum at 24 hours.Hematoxylin-eosin staining revealed pathological impairment of brain tissue at each time point after injury,particularly at 3 days,with nerve cell edema,degeneration,and necrosis observed,and the apoptotic rate significantly increased.Immunohistochemistry and western blot analysis revealed that the expression of occludin at the injured site gradually decreased as injury time advanced and reached a minimum at 3 days after injury;the expression of connexin 43 gradually increased as injury time advanced and reached a peak at 24 hours after injury.The experimental findings indicate that changes in occludin and connexin 43 expression were consistent with the development of brain edema,and may reflect the pathogenesis of brain injury.展开更多
The high-affinity glucocorticoid binding sites（HAGS）and the low-affinity glucocor-ticoid binding sites（LAGS）with steroid specificity were demonstrated in cerebral cytosol ofrats by using the radioligand binding as...The high-affinity glucocorticoid binding sites（HAGS）and the low-affinity glucocor-ticoid binding sites（LAGS）with steroid specificity were demonstrated in cerebral cytosol ofrats by using the radioligand binding assay.The equilibrium dissocation constant（Kd）of HAGSand LAGS were（2.78+0.71）×10<sup>-8</sup>mol/L and（2.12±1.06）×10<sup>-6</sup>mol/L respectively as esti-mated by Scatchard and Pseudoseatchard analysis.Glucocorticoid receptors（GR）in the trau-matized（left）hemisphere cytosol were decreased more significantly than those in both the con-trol（right）hemisphere cytosol at 6 h postinjury and normal brain tissue（P【0.05）,but Kd ofGR showed no significant changes.GR of liver cytosol at 6h postinjury were more markedly de-creased than normal hepatic cytosol,but Kd of GR underwent no significant changes.These da-ta demonstrate that high-dose glucocorticoid（GC）used in the treatment of traumatic brain ede-ma might maintain target-cell reactions by increasing the production of GC receptor complexesand is most likely to be mediated by LAGS.展开更多
BACKGROUND:Previous studies have demonstrated that aquaporin-4 (AQP4) plays a key role in the formation and resolution of brain edema.However,the molecular mechanisms and role of AQP4 in hypoxia-ischemia-induced brain...BACKGROUND:Previous studies have demonstrated that aquaporin-4 (AQP4) plays a key role in the formation and resolution of brain edema.However,the molecular mechanisms and role of AQP4 in hypoxia-ischemia-induced brain edema remain poorly understood.OBJECTIVE:To establish a newborn animal model of astrocytic oxygen-glucose deprivation and reintroduction,to observe the correlation between AQP4 and cellular volume,and to investigate the role of AQP4 in the development of brain edema following oxygen deprivation and reintroduction.DESIGN,TIME AND SETTING:A comparative experiment was performed at the Experimental Center of West China Second University Hospital between October 2007 and April 2009.MATERIALS:Astrocytes were derived from the neocortex of Sprague Dawley rats aged 3 days.METHODS:Astrocytes were incubated in glucose/serum-free Dulbecco's modified Eagle's medium,followed by 1% oxygen for 6 hours.Finally,oxygen-glucose deprivation and reintroduction models were successfully established.MAIN OUTCOME MEASURES:Real-time polymerase chain reaction and Western blot analysis were used to measure expression of AQP4 mRNA and protein in cultured rat astrocytes following oxygen-glucose deprivation and reintroduction.Astrocytic cellular volume,as determined by [3H]-3-O-methyl-D-glucose,was used to represent the extent of astrocytic swelling.RESULTS:During oxygen-glucose deprivation,AQP4 mRNA and protein expression gradually decreased in astrocytes,whereas cellular volume increased in a time-dependent manner (P < 0.01).Following oxygen-glucose reintroduction,AQP4 mRNA and protein expression was upregulated,peaked at day 7,and then gradually decreased,but still higher than normal levels (P < 0.05).However,cellular volume gradually decreased (P < 0.01),and then reached normal levels at day 7.CONCLUSION:AQP4 expression highly correlated with cellular volume changes,suggesting that AQP4 played an important role in modulating brain water transport in an astrocytic oxygen-glucose deprivation and reintroduction model.展开更多
The present study evaluated the effect of dl-3-n hutylphthalide(NBP),a novel brain protective agent,on brain edema in rats following focal ischemiet. Edema was induced by occluding the right middle cerchral artery (MC...The present study evaluated the effect of dl-3-n hutylphthalide(NBP),a novel brain protective agent,on brain edema in rats following focal ischemiet. Edema was induced by occluding the right middle cerchral artery (MCAO) ,producing permanent focal ischemia in the right eerehral hemlspheme,which developed ipsilateral brain edenaa reproduclbly. Edema was assessed 24 b after MCA occlusion by determining the brain water content from wet and dry weight measurements,and the sodium,potasslum concentrations with ionselective electrodas.In this model,NBP at the dose of 80,160 and 240 mg/kg po 15 min after MCAO prevented from brain edema in a dose-dependent manner. A significant reduction of sodium content and an increase in potassium level wee ohserved in all drug-treated groups. It showed that NBP strongly attenuated brain water entry ,sodium accumulation and potassium loss. Nimodlpine treatment (Smg/kg sc) also reduced brain edemo (P<0. 05). The mesults suggest that & strong anti-edema activity ot NBP may play an important role to contribute to the treatment ot ischemic damage.展开更多
Introduction: Meningiomas are the most common type of extra-axial neoplasm. Peritumoral brain edema (PTBE) can be seen around meningiomas while it may be absent in others. Despite that Ki67 proliferative index has bee...Introduction: Meningiomas are the most common type of extra-axial neoplasm. Peritumoral brain edema (PTBE) can be seen around meningiomas while it may be absent in others. Despite that Ki67 proliferative index has been previously correlated with meningioma grades, no definite relationship has been established in relation to PTBE in meningioma patients. Objective: Correlate the peritumoral brain edema with the Ki67 proliferative index of meningiomas. Patients & Methods: Aclinical prospective study was conducted on 56 patients (47 women, 9 men;mean age 50.89 ± 12.55 years) diagnosed with meningiomas. All patients were evaluated regarding the presence of brain edema surrounding the lesion in pre-operative neuroimaging using T2W and FLAIR MR images. Immunohistochemical staining of Ki67 index (representing proliferative activity) was done. Correlation between presence of PTBE and Ki67 index values was evaluated. Results: PTBE was found in nearly half of the patients (48.2%), while the remaining (51.8%) of patients did not exhibit PTBE in their pre-operative neuroimaging. The mean value of Ki67 index in meningioma patients with PTBE was 4.83% compared to a value of 1.83% in patients without PTBE, P value = 0.014. Conclusion: High Ki67 indices are evident in meningiomas with surrounding peritumoral brain edema (PTBE).展开更多
BACKGROUND:Many studies have evaluated the role of vascular endothelial growth factor(VEGF) in traumatic brain edema and hemorrhagic brain edema. OBJECTIVE:To observe the effects of VEGF expression on permeability of ...BACKGROUND:Many studies have evaluated the role of vascular endothelial growth factor(VEGF) in traumatic brain edema and hemorrhagic brain edema. OBJECTIVE:To observe the effects of VEGF expression on permeability of the blood-brain barrier (BBB) during high-altitude and hypoxia exposure,and to investigate the correlation between VEGF expression and BBB permeability with regard to Evans blue staining and brain edema during high-altitude exposure. DESIGN,TIME AND SETTING:The randomized,controlled,animal study was performed at the Tanggula Etape,Central Laboratory of Chengdu Medical College,and Central Laboratory of General Hospital of Chengdu Military Area Command of Chinese PLA,China,from July 2003 to November 2004. MATERIALS:Quantitative RT-PCR kit(Sigma,USA),VEGF ELISA kit(Biosource,USA),and Evans blue(Jingchun,China) were acquired for this study. METHODS:A total of 180 Wistar rats were equally and randomly assigned to 15 groups:low-altitude (500 m),middle-altitude(2 880 m),high-altitude(4 200 m),super-high-altitude(5 000 m),1,3,5,7,9, 11,13,15,17,19,and 21 days of super high-altitude exposure.Wistar rats were exposed to various altitude gradients to establish a hypoxia model. MAIN OUTCOME MEASURES:Brain water content was calculated according to the wet-to-dry weight ratio.BBB permeability to Evans blue was determined by colorimetric method.VEGF mRNA and protein levels in brain tissues were detected using RT-PCR and double-antibody sandwich ELISA. RESULTS:Brain water content,BBB permeability to Evans blue,and VEGF mRNA and protein levels in brain tissues increased with increasing altitude and prolonged exposure to altitude.The greatest increase was determined on day 9 upon ascending 5 000 m.Simultaneously,VEGF expression positively correlated to BBB permeability of Evans blue and brain water content(r = 0.975,0.917,P<0.01). CONCLUSION:Increased VEGF protein and mRNA expression was responsible for increased BBB permeability,which may be an important mechanism underlying brain edema during high-altitude exposure.展开更多
The amyloid hypothesis states that the buildup ofßamyloid in the brain is the main factor for Alzheimer's disease(AD)pathogenesis.An imbalance betweenßamyloid production andß-amyloid clearance cause...The amyloid hypothesis states that the buildup ofßamyloid in the brain is the main factor for Alzheimer's disease(AD)pathogenesis.An imbalance betweenßamyloid production andß-amyloid clearance causes the advanced stages of the disease,including the development of neurofibrillary tangles containing tau protein.展开更多
Brain homeostasis refe rs to the normal working state of the brain in a certain period,which is impo rtant for overall health and normal life activities.Currently,there is a lack of effective treatment methods for the...Brain homeostasis refe rs to the normal working state of the brain in a certain period,which is impo rtant for overall health and normal life activities.Currently,there is a lack of effective treatment methods for the adverse consequences caused by brain homeostasis imbalance.Snapin is a protein that assists in the formation of neuronal synapses and plays a crucial role in the normal growth and development of synapses.Recently,many researchers have reported the association between snapin and neurologic and psychiatric disorders,demonstrating that snapin can improve brain homeostasis.Clinical manifestations of brain disease often involve imbalances in brain homeostasis and may lead to neurological and behavioral sequelae.This article aims to explo re the role of snapin in restoring brain homeostasis after injury or diseases,highlighting its significance in maintaining brain homeostasis and treating brain diseases.Additionally,it comprehensively discusses the implications of snapin in other extracerebral diseases such as diabetes and viral infections,with the objective of determining the clinical potential of snapin in maintaining brain homeostasis.展开更多
AIM:To evaluate the effectiveness and safety of intravitreal ranibizumab(IVR)for diabetic macular edema(DME)in vitrectomized versus non-vitrectomized eyes.METHODS:The PubMed,EMBASE,Web of Science,Cochrane,EBSCO were c...AIM:To evaluate the effectiveness and safety of intravitreal ranibizumab(IVR)for diabetic macular edema(DME)in vitrectomized versus non-vitrectomized eyes.METHODS:The PubMed,EMBASE,Web of Science,Cochrane,EBSCO were comprehensively searched for studies comparing vitrectomized and non-vitrectomized eyes with DME.Clinical outcomes of best-corrected visual acuity(BCVA),central macular thickness(CMT),the mean number of intravitreal injection and adverse events were extracted and analyzed.RESULTS:Six studies involving 641 eyes were included.Final visual gain significantly improved and CMT significantly reduced in vitrectomized eyes at 6mo and 12mo visits(P<0.05).Although the mean reduction in CMT among non-vitrectomized eyes was significantly greater than in vitrectomized eyes at the 6mo[mean difference(MD)=53.57,95%confidence interval(CI):28.03 to 78.72,P<0.0001]and 12mo(MD=49.65,95%CI:19.58 to 79.72,P=0.01),no significant difference was detected in improvement in BCVA at either 6mo(MD=0.05,95%CI:-0.02 to 0.13,P=0.14)or 12mo(MD=0.03,95%CI:-0.04 to 0.09,P=0.43).Injection number of ranibizumab in non-vitrectomized eyes was significantly less than that in vitrectomized eyes during 6-month period(MD=0.60,95%CI:0.16 to 1.04,P=0.008),while there was no statistically significant difference between the two groups during 12mo of follow-up.CONCLUSION:Evidence from current study suggests that IVR was useful for both vitrectomized group and nonvitrectomized group with DME.Although less reduction in macular thickness is found in vitrectomized group,visual improvement between two groups is similar.展开更多
基金Supported by the Epilepsy Research Fund of Chinese Anti-Epilepsy Association,No.CU-A-2021-17Nanjing Municipal Health Bureau key project,No.ZKX21047the Postdoctoral Research Foundation of China,No.2020M671550。
文摘BACKGROUND Early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-1(PEBEL1)is a rare autosomal recessive severe neurometabolic disease.The aim of this study was to investigate the clinical characteristics and genetic pathogenicity of PEBEL1 caused by rare NAXE(or APOA1BP)-related defects.CASE SUMMARY The patient was a girl aged 2 years and 10 mo.She was hospitalized due to walking disorder for>40 d.The clinical manifestations were ataxia,motor function regression,hypotonia,and eyelid ptosis.Within 1 mo of hospitalization,she developed sigh breathing,respiratory failure,cerebellar edema and brain hernia,and finally she died.Changes were found in cranial imaging,including cerebellar edema accompanied by symmetrical myelopathy.Through whole exome sequencing,we detected NAXE compound heterozygous variation(NM 144772.3)c.733A>C(p.Lys245Gln,dbSNP:rs770023429)and novel variation c.370G>T(p.Gly124Cys)in the germline gene.The clinical features and core phenotypes of this case were consistent with 18 previously reported cases of PEBEL1.CONCLUSION This is the first case of NAXE-related PEBEL1 with severe clinical phenotype in China' Mainland.The p.Gly124Cys mutation discovered in this case has enriched the pathogenic variation spectrum of NAXE.
文摘BACKGROUND: Stereo-tactic radiation therapy (SRT) is widely used to treat intracranial diseases, but some patients suffered from radiation induced brain edema after SRT. Once radiation induced brain edema occurs, the treatment is quite difficult, and it always leads to a poor outcome. Dexamethasone has certain therapeutic effect on traumatic brain edema, but the biological mechanism is still unclear. OBJECTIVE: To observe the effect of dexamethasone on the neutrophil expression of CD18. DESIGN: A randomized control observation. SETTING: Changhai Hospital of the Second Military Medical University of Chinese PLA. MATERIALS: The experiment was carried out in Changhai Hospital of the Second Military Medical University of Chinese PLA from January 1999 to December 1999. Twenty SD rats (male and female each in half) weighing (250±50) g were used. METHODS: Twenty SD rats were divided into four groups at random. ① Blank control group (n=5): The rats were not treated without dexamethasone or irradiation; ② Irradiation group (n=5): The rats were given irradiation but no dexamethasone treatment; ③ Irradiation+1 mg/kg dexamethasone group (n=5): The rats were treated with irradiation and dexamethasone of 1 mg/kg; ④ Irradiation+5 mg/kg dexamethasone group (n=5): The rats were treated with irradiation and dexamethasone of 5 mg/kg. The heads of the rats were irradiated with 10 MeV X-ray (30 Gy), and brain tissue was removed after 2 weeks to observe the pathological changes. Blood samples were taken from the carotid artery, gradient centrifugation was used, and neutrophile layer was obtained, the level of neutrophile expression of CD18 mRNA and quantity of membrane proteins in blood were detected with Northern blot and flow cytometry respectively. MAIN OUTCOME MEASURES: ① Blood cell count; ② Pathological results; ③ level of neutrophile expression of CD18 mRNA and quantity of membrane proteins. RESULTS: All the 20 SD rats were involved in the analysis of results without deletion. At 2 weeks after irradiation, obvious cell injury could be observed under light microscope. The level of neutrophile expression of CD18 mRNA and quantity of membrane proteins in blood were obviously increased, but the severity of cell injury was relieved in the irradiation+1 and 5 mg/kg dexamethasone groups, and the CD18 expression was markedly suppressed (P < 0.05), and the suppression was more obvious in the irradiation+5 mg/kg dexamethasone group than in the irradiation+1 mg/kg dexamethasone group (P < 0.01). CONCLUSION: Dexamethasone can reduce the radiation induced brain edema by inhibiting the expression of CD18.
基金General program of Chongqing Natural Science Foundation(No.cstc2019jcyj-msxmx0353)Science and technology program of Banan District of Chongqing(No.018-25)
文摘The aquaporin-4(AQP4)is a highly selective membrane protein.It is important for the body to maintain the water balance between internal and external environment of cells,the studies have found that the abnormal expression of AQP4 is related to the occurrence of many diseases.The cerebral edema is the most common and serious complication of brain trauma,and its pathogenesis is closely related to AQP4.The development of multimodal magnetic resonance imaging(M-MRI)could been provided imaging basis for accurate diagnosis of traumatic brain edema.In recent years,the correlation between AQP4 and M-MRI has become a hotspot of research.This paper reviews the research progress on the correlation between AQP4 expression in traumatic cerebral edema and M-MRI.
文摘Objective: To determine whether VEGF plays a role in the development of peritumoral brain edema. Methods 50 meningioma patients and their VEGF expression were studied. We took a monoclonal antibody from mouse to VEGF to stain the tumor cells, the vascular endothelial cells and the interstitial cells. The severity of brain edema was evaluated according to CT or MR scans by the following equation: edema index= V tumor +edema /Vtumor. The relationship between VEGF expression and edema index was analyzed statistically. Results VEGF was expressed in meningioma tumor cells, which is usually concentrated at the peripheral sites of the tumor. There was a positive linear correlation between the expression and the brain edema index. Conclusion VEGF may play a role in the development of peritumoral brain edema in meningioma patient.
文摘Intracranial hypertension is a major cause of morbidity and mortality of patients suffering from fulminant hepatic failure. The etiology of this intracranial hypertension is not fully determined, and is probably multifactorial, combining a cytotoxic brain edema due to the astrocytic accumulation of glutamine, and an increase in cerebral blood volume and cerebral blood flow, in part due to inflammation, to glutamine and to toxic products of the diseased liver. Validated methods to control intracranial hypertension in fulminant hepatic failure patients mainly include mannitol, hypertonic saline, indomethacin, thiopental, and hyperventilation. However all these measures are often not sufficient in absence of liver transplantation, the only curative treatment of intracranial hypertension in fulminant hepatic failure to date. Induced moderate hypothermia seems very promising in this setting, but has to be validated by a controlled, randomized study. Artificial liver support systems have been under investigation for many decades. The bioartificial liver, based on both detoxification and swine liver cells, has shown some efficacy on reduction of intracranial pressure but did not show survival benefit in a controlled, randomized study. The Molecular Adsorbents Recirculating System has shown some efficacy in decreasing intracranial pressure in an animal model of liver failure, but has still to be evaluated in a phase Ⅲ trial.
文摘OBJECTIVE:To investigate the relationship of aquaporin 4(AQP4)and brain edema.DATA SOURCES:Using the terms of "aquaporin-4,brain edema",we searched PubMed database to identify studies published from January 1997 to April 2006 in the English languages.Meanwhile,we also searched China National Knowledge Infrastructure(CNKI)for related studies.STUDY SELECTION:The collected data were selected firstly.Studies on AQP4 and brain edema were chosen and their full-texts were searched for,and those with repetitive or review studies were excluded.DATA EXTRACTION:Totally 146 related studies were collected,42 of them were involved and the other 104 studies were used for reading reference data.DATA SYNTHESIS:AQP4 is a selective water permeable integral membrane protein.It is mainly expressed in astrocytes and ependymocyte,and is the important structural basis for water regulation and transportation between glial cells and cerebrospinal fluid or vessels.Phosphorylation is involved in the regulation of AQP4.AQP4 participates in the formation of brain edema caused by various factors.Studies on the structure and pathological changes of AQP4 are still in the initial stage,and the role and mechanism of AQP4 in the formation of brain edema is very unclear.CONCLUSION:AQP4 plays a critical regulating role in the formation of ischemic brain edema,but whether it is regulated by drugs lacks reliable evidence.
基金Supported by A grant from the Instituto de Salud CarlosTM,PI051371,PI080809
文摘AIM:To compare rifaximin and insulin-like growth factor(IGF)-1 treatment of hyperammonemia and brain edema in cirrhotic rats with portal occlusion.METHODS:Rats with CCl4-induced cirrhosis with ascites plus portal vein occlusion and controls were randomized into six groups:Cirrhosis;Cirrhosis + IGF-1;Cirrhosis + rifaximin;Controls;Controls + IGF-1;and Controls + rifaximin.An oral glutamine-challenge test was performed,and plasma and cerebral ammonia,glucose,bilirubin,transaminases,endotoxemia,brain water content and ileocecal cultures were measured and liver histology was assessed.RESULTS:Rifaximin treatment significantly reduced bacterial overgrowth and endotoxemia compared with cirrhosis groups,and improved some liver function parameters(bilirubin,alanine aminotransferase and aspartate aminotransferase).These effects were associated with a significant reduction in cerebral water content.Blood and cerebral ammonia levels,and area-underthe-curve values for oral glutamine-challenge tests were similar in rifaximin-treated cirrhotic rats and control group animals.By contrast,IGF-1 administration failed to improve most alterations observed in cirrhosis.CONCLUSION:By reducing gut bacterial overgrowth,only rifaximin was capable of normalizing plasma and brain ammonia and thereby abolishing low-grade brain edema,alterations associated with hepatic encephalopathy.
基金Supported by Grant #TB 56 from the University of Buenos Aires,Argentina
文摘AIM: To study the blood-brain barrier integrity, brain edema,animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication.METHODS: Adults male Wistar rats were divided into four groups. Group I: sham operation; II: Prehepatic portal hypertension, produced by partial portal vein ligation; III:Acetaminophen intoxication and IV: Prehepatic portal hypertension plus acetaminophen. Acetaminophen was administered to produce acute hepatic injury. Portal pressure, liver serum enzymes and ammonia plasma levels were determined. Brain cortex water content was registered and trypan blue was utilized to study blood brain barrier integrity. Reflexes and behavioral tests were recorded.RESULTS: Portal hypertension was significantly elevated in groups II and IV. Liver enzymes and ammonia plasma levels were increased in groups II, III and IV. Prehepatic portal hypertension (group II), acetaminophen intoxication (group III) and both (group IV) had changes in the blood brain-barrier integrity (trypan blue) and hyperammonemia. Cortical edema was present in rats with acute hepatic injury in groups III and IV. Behavioral test (rota rod) was altered in group IV.CONCLUSION: These results suggest the possibility of another pathway for cortical edema production because blood brain barrier was altered (vasogenic) and hyperammonemia was registered (cytotoxic). Group IV, with behavioral altered test, can be considered as a model for study at an early stage of portal-systemic encephalopathy.
基金supported by a grant for Scientific Research Program from the Health Bureau of Henan Province (No.200202)
文摘To investigate the role of AQP9 in brain edema, the expression of AQP9 in an infectious rat brain edema model induced by the injection of lipopolysaccharide (LPS) was examined. Immuno-histochemistry and reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated that the expressions of AQP9 mRNA and protein at all observed intervals were significantly increased in LPS-treated animals in comparison with the control animals. Time-course analysis showed that the first signs of blood-brain barrier disruption and the increase of brain water content in LPS-treated animals were evident 6 h after LPS injection, with maximum value appearing at 12 h, which coincided with the expression profiles of AQP9 mRNA and protein in LPS-treated animals. The further correlation analysis revealed strong positive correlations among the brain water content, the disruption of the blood-brain barrier and the enhanced expressions of AQP9 mRNA and protein in LPS-treated animals. These results suggested that the regulation of AQP9 expression may play important roles in water movement and in brain metabolic homeostasis associated with the pathophysiology of brain edema induced by LPS injection.
基金supported by the Natural Science Foundation of Guangdong Province,No.10151600101000002
文摘The experimental model of traumatic brain injury was established in Sprague-Dawley rats according to Feeney’s free falling method.The brains were harvested at 2,6 and 24 hours,and at 3 and 5days after injury.Changes in brain water content were determined using the wet and dry weights.Our results showed that water content of tissue significantly increased after traumatic brain injury,and reached minimum at 24 hours.Hematoxylin-eosin staining revealed pathological impairment of brain tissue at each time point after injury,particularly at 3 days,with nerve cell edema,degeneration,and necrosis observed,and the apoptotic rate significantly increased.Immunohistochemistry and western blot analysis revealed that the expression of occludin at the injured site gradually decreased as injury time advanced and reached a minimum at 3 days after injury;the expression of connexin 43 gradually increased as injury time advanced and reached a peak at 24 hours after injury.The experimental findings indicate that changes in occludin and connexin 43 expression were consistent with the development of brain edema,and may reflect the pathogenesis of brain injury.
文摘The high-affinity glucocorticoid binding sites（HAGS）and the low-affinity glucocor-ticoid binding sites（LAGS）with steroid specificity were demonstrated in cerebral cytosol ofrats by using the radioligand binding assay.The equilibrium dissocation constant（Kd）of HAGSand LAGS were（2.78+0.71）×10<sup>-8</sup>mol/L and（2.12±1.06）×10<sup>-6</sup>mol/L respectively as esti-mated by Scatchard and Pseudoseatchard analysis.Glucocorticoid receptors（GR）in the trau-matized（left）hemisphere cytosol were decreased more significantly than those in both the con-trol（right）hemisphere cytosol at 6 h postinjury and normal brain tissue（P【0.05）,but Kd ofGR showed no significant changes.GR of liver cytosol at 6h postinjury were more markedly de-creased than normal hepatic cytosol,but Kd of GR underwent no significant changes.These da-ta demonstrate that high-dose glucocorticoid（GC）used in the treatment of traumatic brain ede-ma might maintain target-cell reactions by increasing the production of GC receptor complexesand is most likely to be mediated by LAGS.
基金the National Natural Science Foundation of China,No.30825039,30973236,30872346,30770748Chinese Postdoctoral Training Grant,No. 20070420575+1 种基金Application Basic Research Foundation of Sichuan Province,No. 2008JY0131Youth Science and Technology Foundation of Sichuan Province,No. 07zq026-135
文摘BACKGROUND:Previous studies have demonstrated that aquaporin-4 (AQP4) plays a key role in the formation and resolution of brain edema.However,the molecular mechanisms and role of AQP4 in hypoxia-ischemia-induced brain edema remain poorly understood.OBJECTIVE:To establish a newborn animal model of astrocytic oxygen-glucose deprivation and reintroduction,to observe the correlation between AQP4 and cellular volume,and to investigate the role of AQP4 in the development of brain edema following oxygen deprivation and reintroduction.DESIGN,TIME AND SETTING:A comparative experiment was performed at the Experimental Center of West China Second University Hospital between October 2007 and April 2009.MATERIALS:Astrocytes were derived from the neocortex of Sprague Dawley rats aged 3 days.METHODS:Astrocytes were incubated in glucose/serum-free Dulbecco's modified Eagle's medium,followed by 1% oxygen for 6 hours.Finally,oxygen-glucose deprivation and reintroduction models were successfully established.MAIN OUTCOME MEASURES:Real-time polymerase chain reaction and Western blot analysis were used to measure expression of AQP4 mRNA and protein in cultured rat astrocytes following oxygen-glucose deprivation and reintroduction.Astrocytic cellular volume,as determined by [3H]-3-O-methyl-D-glucose,was used to represent the extent of astrocytic swelling.RESULTS:During oxygen-glucose deprivation,AQP4 mRNA and protein expression gradually decreased in astrocytes,whereas cellular volume increased in a time-dependent manner (P < 0.01).Following oxygen-glucose reintroduction,AQP4 mRNA and protein expression was upregulated,peaked at day 7,and then gradually decreased,but still higher than normal levels (P < 0.05).However,cellular volume gradually decreased (P < 0.01),and then reached normal levels at day 7.CONCLUSION:AQP4 expression highly correlated with cellular volume changes,suggesting that AQP4 played an important role in modulating brain water transport in an astrocytic oxygen-glucose deprivation and reintroduction model.
文摘The present study evaluated the effect of dl-3-n hutylphthalide(NBP),a novel brain protective agent,on brain edema in rats following focal ischemiet. Edema was induced by occluding the right middle cerchral artery (MCAO) ,producing permanent focal ischemia in the right eerehral hemlspheme,which developed ipsilateral brain edenaa reproduclbly. Edema was assessed 24 b after MCA occlusion by determining the brain water content from wet and dry weight measurements,and the sodium,potasslum concentrations with ionselective electrodas.In this model,NBP at the dose of 80,160 and 240 mg/kg po 15 min after MCAO prevented from brain edema in a dose-dependent manner. A significant reduction of sodium content and an increase in potassium level wee ohserved in all drug-treated groups. It showed that NBP strongly attenuated brain water entry ,sodium accumulation and potassium loss. Nimodlpine treatment (Smg/kg sc) also reduced brain edemo (P<0. 05). The mesults suggest that & strong anti-edema activity ot NBP may play an important role to contribute to the treatment ot ischemic damage.
文摘Introduction: Meningiomas are the most common type of extra-axial neoplasm. Peritumoral brain edema (PTBE) can be seen around meningiomas while it may be absent in others. Despite that Ki67 proliferative index has been previously correlated with meningioma grades, no definite relationship has been established in relation to PTBE in meningioma patients. Objective: Correlate the peritumoral brain edema with the Ki67 proliferative index of meningiomas. Patients & Methods: Aclinical prospective study was conducted on 56 patients (47 women, 9 men;mean age 50.89 ± 12.55 years) diagnosed with meningiomas. All patients were evaluated regarding the presence of brain edema surrounding the lesion in pre-operative neuroimaging using T2W and FLAIR MR images. Immunohistochemical staining of Ki67 index (representing proliferative activity) was done. Correlation between presence of PTBE and Ki67 index values was evaluated. Results: PTBE was found in nearly half of the patients (48.2%), while the remaining (51.8%) of patients did not exhibit PTBE in their pre-operative neuroimaging. The mean value of Ki67 index in meningioma patients with PTBE was 4.83% compared to a value of 1.83% in patients without PTBE, P value = 0.014. Conclusion: High Ki67 indices are evident in meningiomas with surrounding peritumoral brain edema (PTBE).
基金Supported by:the Tackle Key Problem in Science and Technology during the "11~(th) Five-Year Plan" Period of Chinese PLA,No.06G030
文摘BACKGROUND:Many studies have evaluated the role of vascular endothelial growth factor(VEGF) in traumatic brain edema and hemorrhagic brain edema. OBJECTIVE:To observe the effects of VEGF expression on permeability of the blood-brain barrier (BBB) during high-altitude and hypoxia exposure,and to investigate the correlation between VEGF expression and BBB permeability with regard to Evans blue staining and brain edema during high-altitude exposure. DESIGN,TIME AND SETTING:The randomized,controlled,animal study was performed at the Tanggula Etape,Central Laboratory of Chengdu Medical College,and Central Laboratory of General Hospital of Chengdu Military Area Command of Chinese PLA,China,from July 2003 to November 2004. MATERIALS:Quantitative RT-PCR kit(Sigma,USA),VEGF ELISA kit(Biosource,USA),and Evans blue(Jingchun,China) were acquired for this study. METHODS:A total of 180 Wistar rats were equally and randomly assigned to 15 groups:low-altitude (500 m),middle-altitude(2 880 m),high-altitude(4 200 m),super-high-altitude(5 000 m),1,3,5,7,9, 11,13,15,17,19,and 21 days of super high-altitude exposure.Wistar rats were exposed to various altitude gradients to establish a hypoxia model. MAIN OUTCOME MEASURES:Brain water content was calculated according to the wet-to-dry weight ratio.BBB permeability to Evans blue was determined by colorimetric method.VEGF mRNA and protein levels in brain tissues were detected using RT-PCR and double-antibody sandwich ELISA. RESULTS:Brain water content,BBB permeability to Evans blue,and VEGF mRNA and protein levels in brain tissues increased with increasing altitude and prolonged exposure to altitude.The greatest increase was determined on day 9 upon ascending 5 000 m.Simultaneously,VEGF expression positively correlated to BBB permeability of Evans blue and brain water content(r = 0.975,0.917,P<0.01). CONCLUSION:Increased VEGF protein and mRNA expression was responsible for increased BBB permeability,which may be an important mechanism underlying brain edema during high-altitude exposure.
文摘The amyloid hypothesis states that the buildup ofßamyloid in the brain is the main factor for Alzheimer's disease(AD)pathogenesis.An imbalance betweenßamyloid production andß-amyloid clearance causes the advanced stages of the disease,including the development of neurofibrillary tangles containing tau protein.
基金supported by the National Natural Science Foundation of China,Nos.82071382(to MZ),81601306(to HS)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)(to MZ)+5 种基金Jiangsu 333 High Level Talent Training Project(2022)(to HS)the Jiangsu Maternal and Child Health Research Key Project(F202013)(to HS)Jiangsu Talent Youth Medical Program,No.QNRC2016245(to HS)Shanghai Key Lab of Forensic Medicine,No.KF2102(to MZ)Suzhou Science and Technology Development Project,No.SYS2020089(to MZ)the Fifth Batch of Gusu District Health Talent Training Project,No.GSWS2019060(to HS)。
文摘Brain homeostasis refe rs to the normal working state of the brain in a certain period,which is impo rtant for overall health and normal life activities.Currently,there is a lack of effective treatment methods for the adverse consequences caused by brain homeostasis imbalance.Snapin is a protein that assists in the formation of neuronal synapses and plays a crucial role in the normal growth and development of synapses.Recently,many researchers have reported the association between snapin and neurologic and psychiatric disorders,demonstrating that snapin can improve brain homeostasis.Clinical manifestations of brain disease often involve imbalances in brain homeostasis and may lead to neurological and behavioral sequelae.This article aims to explo re the role of snapin in restoring brain homeostasis after injury or diseases,highlighting its significance in maintaining brain homeostasis and treating brain diseases.Additionally,it comprehensively discusses the implications of snapin in other extracerebral diseases such as diabetes and viral infections,with the objective of determining the clinical potential of snapin in maintaining brain homeostasis.
文摘AIM:To evaluate the effectiveness and safety of intravitreal ranibizumab(IVR)for diabetic macular edema(DME)in vitrectomized versus non-vitrectomized eyes.METHODS:The PubMed,EMBASE,Web of Science,Cochrane,EBSCO were comprehensively searched for studies comparing vitrectomized and non-vitrectomized eyes with DME.Clinical outcomes of best-corrected visual acuity(BCVA),central macular thickness(CMT),the mean number of intravitreal injection and adverse events were extracted and analyzed.RESULTS:Six studies involving 641 eyes were included.Final visual gain significantly improved and CMT significantly reduced in vitrectomized eyes at 6mo and 12mo visits(P<0.05).Although the mean reduction in CMT among non-vitrectomized eyes was significantly greater than in vitrectomized eyes at the 6mo[mean difference(MD)=53.57,95%confidence interval(CI):28.03 to 78.72,P<0.0001]and 12mo(MD=49.65,95%CI:19.58 to 79.72,P=0.01),no significant difference was detected in improvement in BCVA at either 6mo(MD=0.05,95%CI:-0.02 to 0.13,P=0.14)or 12mo(MD=0.03,95%CI:-0.04 to 0.09,P=0.43).Injection number of ranibizumab in non-vitrectomized eyes was significantly less than that in vitrectomized eyes during 6-month period(MD=0.60,95%CI:0.16 to 1.04,P=0.008),while there was no statistically significant difference between the two groups during 12mo of follow-up.CONCLUSION:Evidence from current study suggests that IVR was useful for both vitrectomized group and nonvitrectomized group with DME.Although less reduction in macular thickness is found in vitrectomized group,visual improvement between two groups is similar.
