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
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 d...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.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
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
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
Radiation therapy is considered the most effective non-surgical treatment for brain tumors.However,there are no available treatments for radiation-induced brain injury.Bisdemethoxycurcumin(BDMC)is a demethoxy derivati...Radiation therapy is considered the most effective non-surgical treatment for brain tumors.However,there are no available treatments for radiation-induced brain injury.Bisdemethoxycurcumin(BDMC)is a demethoxy derivative of curcumin that has anti-proliferative,anti-inflammatory,and anti-oxidant properties.To determine whether BDMC has the potential to treat radiation-induced brain injury,in this study,we established a rat model of radiation-induced brain injury by administe ring a single 30-Gy vertical dose of irradiation to the whole brain,followed by intraperitoneal injection of 500μL of a 100 mg/kg BDMC solution every day for 5 successive weeks.Our res ults showed that BDMC increased the body weight of rats with radiation-induced brain injury,improved lea rning and memory,attenuated brain edema,inhibited astrocyte activation,and reduced oxidative stress.These findings suggest that BDMC protects against radiationinduced brain injury.展开更多
After traumatic brain injury, vasogenic and cytotoxic edema appear sequentially on the involved side. Neuroimaging investigations of edema on the injured side have employed apparent diffusion coefficient measurements ...After traumatic brain injury, vasogenic and cytotoxic edema appear sequentially on the involved side. Neuroimaging investigations of edema on the injured side have employed apparent diffusion coefficient measurements in diffusion tensor imaging. We investigated the changes occurring on the injured and uninjured sides using diffusion tensor imaging/apparent diffusion coefficient and histological samples in rats. We found that, on the injured side, that vasogenic edema appeared at 1 hour and intracellular edema appeared at 3 hours. Mixed edema was observed at 6 hours, worsening until 12–24 hours post-injury. Simultaneously, microglial cells proliferated at the trauma site. Apparent diffusion coefficient values increased at 1 hour, decreased at 6 hours, and increased at 12 hours. The uninjured side showed no significant pathological change at 1 hour after injury. Cytotoxic edema appeared at 3 hours, and vasogenic edema was visible at 6 hours. Cytotoxic edema persisted, but vasogenic edema tended to decrease after 12–24 hours. Despite this complex edema pattern on the uninjured side with associated pathologic changes, no significant change in apparent diffusion coefficient values was detected over the first 24 hours. Apparent diffusion coefficient values accurately detected the changes on the injured side, but did not detect the changes on the uninjured side, giving a false-negative result.展开更多
Sirtuin 2(SIRT2)inhibition or Sirt2 knocko ut in animal models protects against the development of neurodegenerative diseases and cerebral ischemia.However,the role of SIRT2 in traumatic brain injury(TBI)remains uncle...Sirtuin 2(SIRT2)inhibition or Sirt2 knocko ut in animal models protects against the development of neurodegenerative diseases and cerebral ischemia.However,the role of SIRT2 in traumatic brain injury(TBI)remains unclear.In this study,we found that knockout of Sirt2 in a mouse model of TBI reduced brain edema,attenuated dis ruption of the blood-brain barrie r,decreased expression of the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome,reduced the activity of the effector caspase-1,reduced neuroinflammation and neuronal pyroptosis,and improved neurological function.Knoc kout of Sirt2 in a mechanical stretch injury cell model in vitro also decreased expression of the NLRP3 inflammasome and pyroptosis.Our findings suggest that knockout of Sirt2 is neuro protective against TBI;therefore.Sirt2 could be a novel to rget for TBI treatment.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 treatment of malignant brain tumors remains a challenge. Stem cell technology has been applied in the treatment of brain tumors largely because of the ability of some stem cells to infiltrate into regions within t...The treatment of malignant brain tumors remains a challenge. Stem cell technology has been applied in the treatment of brain tumors largely because of the ability of some stem cells to infiltrate into regions within the brain where tumor cells migrate as shown in preclinical studies. However, not all of these efforts can translate in the effective treatment that improves the quality of life for pa-tients. Here, we perform a literature review to identify the problems in the field. Given the lack of efficacy of most stem cell-based agents used in the treatment of malignant brain tumors, we found that stem cell distribution(i.e., only a fraction of stem cells applied capable of targeting tumors) are among the limiting factors. We provide guidelines for potential improvements in stem cell distribution. Specifically, we use an engineered tissue graft platform that replicates the in vivo microenvironment, and provide our data to validate that this culture platform is viable for producing stem cells that have better stem cell distribution than with the Petri dish culture system.展开更多
The contents of 5-hydroxytryptamine(5-HT)and dopamine(DA) in the brain microvessels(BMVs) at the early stage of rat brain injury were measured by using high performance liquid chromatography with electrochemical detec...The contents of 5-hydroxytryptamine(5-HT)and dopamine(DA) in the brain microvessels(BMVs) at the early stage of rat brain injury were measured by using high performance liquid chromatography with electrochemical detector(HPLC-ECD) and the influence of the展开更多
Recent studies have proposed three lymphatic drainage systems in the brain,that is,the glymphatic system,the intramural periarterial drainage pathway,and meningeal lymphatic vessels,whose roles in various neurological...Recent studies have proposed three lymphatic drainage systems in the brain,that is,the glymphatic system,the intramural periarterial drainage pathway,and meningeal lymphatic vessels,whose roles in various neurological diseases have been widely explored.The glymphatic system is a fluid drainage and waste clearance pathway that utilizes perivascular space and aquaporin-4 protein located in the astrocyte endfeet to provide a space for exchange of cerebrospinal fluid and interstitial fluid.The intramural periarterial drainage pathway drives the flow of interstitial fluid through the capillary basement membrane and the arterial tunica media.Meningeal lymphatic vessels within the dura mater are involved in the removal of cerebral macromolecules and immune responses.After ischemic stroke,impairment of these systems could lead to cerebral edema,accumulation of toxic factors,and activation of neuroinflammation,while restoration of their normal functions can improve neurological outcomes.In this review,we summarize the basic concepts of these drainage systems,including drainage routes,physiological functions,regulatory mechanisms,and detection technologies.We also focus on the roles of lymphatic drainage systems in brain injury after ischemic stroke,as well as recent advances in therapeutic strategies targeting these drainage systems.These findings provide information for potential novel strategies for treatment of stroke.展开更多
High grade gliomas are the commonest intrinsic brain tumours and account for more average years of life lost than all the common cancers. It has become the commonest cause of cancer death in men under the age of 45 an...High grade gliomas are the commonest intrinsic brain tumours and account for more average years of life lost than all the common cancers. It has become the commonest cause of cancer death in men under the age of 45 and women under the age of 35. Although surgical resection can greatly reduce tumour bulk, complete excision is virtually impossible due to the infiltrative nature of these tumours. In an attempt to treat the infiltrating tumour cells, there has been much interest in using local therapies inserted at the time of surgery. The authors report a case of fatal cerebral edema unresponsive to aggressive medical and surgical assessment that finally evolved to premature death in the early postsurgical period, after the craniotomy and implantation of Gliadel wafers. They note that high doses of dexamethasone were insufficient to prevent cerebral edema and death. A search for corticosteroid use and dosing for patients treated with Gliadel wafers in the published literature revealed no recommendations on the doses of steroids to be administered. In our opinion this is a very important issue and maybe the key point for the treatment of this disease, and may need to be addressed with treatment guidelines in the near future in order to ensure better results on patient’s survival. Prior to this case review there had been two similar report but a later presentation. So we think that this is the first case report of acute fulminant cerebral edema secondary to gliadel wafers in the early period.展开更多
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 grants from the National Natural Science Foundation of China(No.81270239)the Natural Science Foundation of Hubei Province of China(No.2014CFB200)
文摘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.
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 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 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 the National Natural Science Foundation of China,No.82002400(to GJZ)Scientific Research Project of Hu nan Health Committee,No.20201911and No.20200469(both to ZJX)+2 种基金Scientific Research Project of Hunan Health Committee,No.20211411761(to HMW)the Natural Science Foundation of Hunan Province,No.2020JJ5512(to GJZ)a grant from Clinical Medical Technology Innovation Guidance Project in Hunan Province,No.2020SK51822(to ZJX)。
文摘Radiation therapy is considered the most effective non-surgical treatment for brain tumors.However,there are no available treatments for radiation-induced brain injury.Bisdemethoxycurcumin(BDMC)is a demethoxy derivative of curcumin that has anti-proliferative,anti-inflammatory,and anti-oxidant properties.To determine whether BDMC has the potential to treat radiation-induced brain injury,in this study,we established a rat model of radiation-induced brain injury by administe ring a single 30-Gy vertical dose of irradiation to the whole brain,followed by intraperitoneal injection of 500μL of a 100 mg/kg BDMC solution every day for 5 successive weeks.Our res ults showed that BDMC increased the body weight of rats with radiation-induced brain injury,improved lea rning and memory,attenuated brain edema,inhibited astrocyte activation,and reduced oxidative stress.These findings suggest that BDMC protects against radiationinduced brain injury.
基金supported by the National Natural Science Foundation of China,No.81160181the International Cooperation Project of Hainan Province,No.Qiongke(2012)65
文摘After traumatic brain injury, vasogenic and cytotoxic edema appear sequentially on the involved side. Neuroimaging investigations of edema on the injured side have employed apparent diffusion coefficient measurements in diffusion tensor imaging. We investigated the changes occurring on the injured and uninjured sides using diffusion tensor imaging/apparent diffusion coefficient and histological samples in rats. We found that, on the injured side, that vasogenic edema appeared at 1 hour and intracellular edema appeared at 3 hours. Mixed edema was observed at 6 hours, worsening until 12–24 hours post-injury. Simultaneously, microglial cells proliferated at the trauma site. Apparent diffusion coefficient values increased at 1 hour, decreased at 6 hours, and increased at 12 hours. The uninjured side showed no significant pathological change at 1 hour after injury. Cytotoxic edema appeared at 3 hours, and vasogenic edema was visible at 6 hours. Cytotoxic edema persisted, but vasogenic edema tended to decrease after 12–24 hours. Despite this complex edema pattern on the uninjured side with associated pathologic changes, no significant change in apparent diffusion coefficient values was detected over the first 24 hours. Apparent diffusion coefficient values accurately detected the changes on the injured side, but did not detect the changes on the uninjured side, giving a false-negative result.
基金supported by the National Nature Science Foundation of China,Nos.81671207 and 81974189(both to HLT)。
文摘Sirtuin 2(SIRT2)inhibition or Sirt2 knocko ut in animal models protects against the development of neurodegenerative diseases and cerebral ischemia.However,the role of SIRT2 in traumatic brain injury(TBI)remains unclear.In this study,we found that knockout of Sirt2 in a mouse model of TBI reduced brain edema,attenuated dis ruption of the blood-brain barrie r,decreased expression of the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome,reduced the activity of the effector caspase-1,reduced neuroinflammation and neuronal pyroptosis,and improved neurological function.Knoc kout of Sirt2 in a mechanical stretch injury cell model in vitro also decreased expression of the NLRP3 inflammasome and pyroptosis.Our findings suggest that knockout of Sirt2 is neuro protective against TBI;therefore.Sirt2 could be a novel to rget for TBI treatment.
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.
基金Supported by The CHOC Children’s Foundation,CHOC Neuroscience Institute,CHOC Research Institute,The Austin Ford Tribute and Keck Foundationby The United States National Institutes of Health,1R01CA164509-01The United States National Science Foundation,CHE-1213161
文摘The treatment of malignant brain tumors remains a challenge. Stem cell technology has been applied in the treatment of brain tumors largely because of the ability of some stem cells to infiltrate into regions within the brain where tumor cells migrate as shown in preclinical studies. However, not all of these efforts can translate in the effective treatment that improves the quality of life for pa-tients. Here, we perform a literature review to identify the problems in the field. Given the lack of efficacy of most stem cell-based agents used in the treatment of malignant brain tumors, we found that stem cell distribution(i.e., only a fraction of stem cells applied capable of targeting tumors) are among the limiting factors. We provide guidelines for potential improvements in stem cell distribution. Specifically, we use an engineered tissue graft platform that replicates the in vivo microenvironment, and provide our data to validate that this culture platform is viable for producing stem cells that have better stem cell distribution than with the Petri dish culture system.
文摘The contents of 5-hydroxytryptamine(5-HT)and dopamine(DA) in the brain microvessels(BMVs) at the early stage of rat brain injury were measured by using high performance liquid chromatography with electrochemical detector(HPLC-ECD) and the influence of the
基金supported by the Natural Science Foundation of Beijing(Key Program)No.Z200025(to JHY)+1 种基金the National Natural Science Foundation of China,No.81873818(to LHQ)Supporting Platform Construction Project of Peking University Health Science Center,No.BMU2021ZC011(to JHY).
文摘Recent studies have proposed three lymphatic drainage systems in the brain,that is,the glymphatic system,the intramural periarterial drainage pathway,and meningeal lymphatic vessels,whose roles in various neurological diseases have been widely explored.The glymphatic system is a fluid drainage and waste clearance pathway that utilizes perivascular space and aquaporin-4 protein located in the astrocyte endfeet to provide a space for exchange of cerebrospinal fluid and interstitial fluid.The intramural periarterial drainage pathway drives the flow of interstitial fluid through the capillary basement membrane and the arterial tunica media.Meningeal lymphatic vessels within the dura mater are involved in the removal of cerebral macromolecules and immune responses.After ischemic stroke,impairment of these systems could lead to cerebral edema,accumulation of toxic factors,and activation of neuroinflammation,while restoration of their normal functions can improve neurological outcomes.In this review,we summarize the basic concepts of these drainage systems,including drainage routes,physiological functions,regulatory mechanisms,and detection technologies.We also focus on the roles of lymphatic drainage systems in brain injury after ischemic stroke,as well as recent advances in therapeutic strategies targeting these drainage systems.These findings provide information for potential novel strategies for treatment of stroke.
文摘High grade gliomas are the commonest intrinsic brain tumours and account for more average years of life lost than all the common cancers. It has become the commonest cause of cancer death in men under the age of 45 and women under the age of 35. Although surgical resection can greatly reduce tumour bulk, complete excision is virtually impossible due to the infiltrative nature of these tumours. In an attempt to treat the infiltrating tumour cells, there has been much interest in using local therapies inserted at the time of surgery. The authors report a case of fatal cerebral edema unresponsive to aggressive medical and surgical assessment that finally evolved to premature death in the early postsurgical period, after the craniotomy and implantation of Gliadel wafers. They note that high doses of dexamethasone were insufficient to prevent cerebral edema and death. A search for corticosteroid use and dosing for patients treated with Gliadel wafers in the published literature revealed no recommendations on the doses of steroids to be administered. In our opinion this is a very important issue and maybe the key point for the treatment of this disease, and may need to be addressed with treatment guidelines in the near future in order to ensure better results on patient’s survival. Prior to this case review there had been two similar report but a later presentation. So we think that this is the first case report of acute fulminant cerebral edema secondary to gliadel wafers in the early period.
