PURPOSE: Hypertonic fluids such as mannitol and half-molar sodium lactate are given to treat intracranial hypertension in patients with severe traumatic brain injury (TBI). In this study, sodium lactate was compared to mannitol in patients with TBI to investigate the efficacy in reducing intracranial pressure (ICP). METHODS: This study was a systematic review with literature research on articles published in any year in the databases of PubMed, ScienceDirect, Asian Journal of Neurosurgery, and Cochrane Central Register of Controlled Trials. The keywords were "half-molar sodium lactate", "mannitol", "cerebral edema or brain swelling", and "severe traumatic brain injury". The inclusion criteria were (1) studies published in English, (2) randomized control trials or retrospective/prospective studies on TBI patients, and (3) therapies including half-molar sodium lactate and mannitol and (4) sufficient data such as mean difference (MD) and risk ratio (RR). Data analysis was conducted using Review Manager 5.3. RESULTS: From 1499 studies, a total of 8 studies were eligible. Mannitol group reduced ICP of 0.65 times (MD 0.65; p = 0.64) and improved cerebral perfusion pressure of 0.61 times (MD 0.61; p = 0.88), better than the half-molar group of sodium lactate. But the half-molar group of sodium lactate maintained the mean arterial pressure level of 0.86 times, better than the mannitol group (MD 0.86; p = 0.09). CONCLUSION Half-molar sodium lactate is as effective as mannitol in reducing ICP in the early phase of brain injury, superior over mannitol in an extended period. It is able to prevent intracranial hypertension and give better brain tissue perfusion as well as more stable hemodynamics. Blood osmolarity is a concern as it increases serum sodium.
Brain Edema ; Brain Injuries, Traumatic/drug therapy* ; Diuretics, Osmotic/therapeutic use* ; Humans ; Intracranial Hypertension/etiology* ; Intracranial Pressure ; Mannitol/therapeutic use* ; Prospective Studies ; Retrospective Studies ; Saline Solution, Hypertonic ; Sodium Lactate

OBJECTIVE: To investigate the effects of blocking the activation of ERK pathway on the expression of matrix metalloproteinase-9 (MMP-9) and the formation of cerebral edema in SD rats after brain injury. METHODS: Ninety SD rats were randomly divided into 3 equal groups, including a sham-operated group, modified Feeney's traumatic brain injury model group, and ERK inhibition group where the ERK inhibitor SCH772984 (500 μg/kg) was injected via the femoral vein 15 min before brain trauma. At 2 h and 2 days after brain trauma, the permeability of blood-brain barrier was assessed by Evans blue method, the water content of the brain tissue was determined, and the phosphorylation level of ERK and the expression level of MMP-9 mRNA and protein were measured by RT-PCR and Western blotting. RESULTS: Compared with the sham-operated group, the rats with brain trauma exhibited significantly increased level of ERK phosphorylation at 2 h and significantly increased expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). Treatment with the ERK inhibitor significantly decreased the phosphorylation level of ERK after the injury ( < 0.01), suppressed over-expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). The permeability of blood-brain barrier increased significantly 2 h after brain trauma ( < 0.05) and increased further at 2 days ( < 0.01); the water content of the brain did not change significantly at 2 h ( > 0.05) but increased significantly 2 d after the injury ( < 0.01). Treatment with the ERK inhibitor significantly lowered the permeability of blood-brain barrier and brain water content after brain trauma ( < 0.01). CONCLUSIONS Blocking the activation of ERK pathway significantly reduced the over-expression of MMP-9 and alleviates the damage of blood-brain barrier and traumatic brain edema, suggesting that ERK signaling pathway plays an important role in traumatic brain edema by regulating the expression of MMP-9.
Animals ; Brain Edema ; drug therapy ; etiology ; Brain Injuries, Traumatic ; complications ; drug therapy ; Gene Expression Regulation, Enzymologic ; drug effects ; Indazoles ; pharmacology ; therapeutic use ; MAP Kinase Signaling System ; drug effects ; Matrix Metalloproteinase 9 ; genetics ; Piperazines ; pharmacology ; therapeutic use ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Gastrodin is a phenolic glycoside that has been demonstrated to provide neuroprotection in preclinical models of central nervous system disease, but its effect in subarachnoid hemorrhage (SAH) remains unclear. In this study, we showed that intraperitoneal administration of gastrodin (100 mg/kg per day) significantly attenuated the SAH-induced neurological deficit, brain edema, and increased blood-brain barrier permeability in rats. Meanwhile, gastrodin treatment significantly reduced the SAH-induced elevation of glutamate concentration in the cerebrospinal fluid and the intracellular Ca overload. Moreover, gastrodin suppressed the SAH-induced microglial activation, astrocyte activation, and neuronal apoptosis. Mechanistically, gastrodin significantly reduced the oxidative stress and inflammatory response, up-regulated the expression of nuclear factor erythroid 2-related factor 2, heme oxygenase-1, phospho-Akt and B-cell lymphoma 2, and down-regulated the expression of BCL2-associated X protein and cleaved caspase-3. Our results suggested that the administration of gastrodin provides neuroprotection against early brain injury after experimental SAH.
Animals ; Apoptosis ; drug effects ; Astrocytes ; drug effects ; metabolism ; Benzyl Alcohols ; administration & dosage ; Blood-Brain Barrier ; drug effects ; metabolism ; Brain ; drug effects ; metabolism ; Brain Edema ; etiology ; prevention & control ; Calcium ; metabolism ; Glucosides ; administration & dosage ; Glutamic Acid ; metabolism ; Male ; Microglia ; drug effects ; metabolism ; Neurons ; drug effects ; Neuroprotective Agents ; administration & dosage ; Oxidative Stress ; drug effects ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage ; complications ; metabolism ; prevention & control

Fluoxetine, an anti-depressant drug, has recently been shown to provide neuroprotection in central nervous system injury, but its roles in subarachnoid hemorrhage (SAH) remain unclear. In this study, we aimed to evaluate whether fluoxetine attenuates early brain injury (EBI) after SAH. We demonstrated that intraperitoneal injection of fluoxetine (10 mg/kg per day) significantly attenuated brain edema and blood-brain barrier (BBB) disruption, microglial activation, and neuronal apoptosis in EBI after experimental SAH, as evidenced by the reduction of brain water content and Evans blue dye extravasation, prevention of disruption of the tight junction proteins zonula occludens-1, claudin-5, and occludin, a decrease of cells staining positive for Iba-1, ED-1, and TUNEL and a decline in IL-1β, IL-6, TNF-α, MDA, 3-nitrotyrosine, and 8-OHDG levels. Moreover, fluoxetine significantly improved the neurological deficits of EBI and long-term sensorimotor behavioral deficits following SAH in a rat model. These results indicated that fluoxetine has a neuroprotective effect after experimental SAH.
Animals ; Apoptosis ; drug effects ; Blood-Brain Barrier ; drug effects ; Brain Edema ; drug therapy ; etiology ; Cytokines ; genetics ; metabolism ; Disease Models, Animal ; Fluoxetine ; pharmacology ; therapeutic use ; In Situ Nick-End Labeling ; Male ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Pain Measurement ; Psychomotor Performance ; drug effects ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage ; complications ; drug therapy ; pathology ; Time Factors ; Vasospasm, Intracranial ; drug therapy ; etiology

OBJECTIVETo investigate the role of miRNA-210 in hypoxic-ischemic brain edema in neonatal rats.

METHODSA total of 80 neonatal rats were randomly divided into control group, normal saline group, miRNA-210 expression inhibition group, and miRNA-210 overexpression group, with 20 rats in each group. Each group was randomly divided into sham-operation group and hypoxia-ischemia (HI) group, with 10 rats in each group. The neonatal rats in the HI group were treated with ligation of the left common carotid artery and then put in a hypoxia cabin with mixed gas of 8% O2 and 92% N2 for 2 hours; those in the sham-operation group were treated with isolation of the left common carotid artery only, without ligation or hypoxia treatment. After HI or sham-operation, the rats in the normal saline group, miRNA-210 expression inhibition group, and miRNA-210 overexpression group were intracranially injected with normal saline (2.5 mg/kg), miRNA-210 inhibitor (2.5 mg/kg), and miRNA-210 mimic (2.5 mg/kg) respectively. No treatment was given to the rats in the control group. The rats were sacrificed three days later, and the left brain tissue was harvested. Fluorescent quantitative PCR was used to measure the expression of miRNA-210; the dry-wet weight method was used to measure the water content of brain tissue; hematoxylin and eosin staining was used to observe the histomorphological changes in the brain.

RESULTSThe HI groups showed significant reductions in the expression of miRNA-210 and significant increases in the water content of brain tissue compared with the corresponding sham-operation groups (P<0.05). Compared with the normal saline HI group, the miRNA-210 expression inhibition HI group showed a significant reduction in the expression of miRNA-210 and a significant increase in the water content of brain tissue (P<0.05), and the miRNA-210 overexpression HI group showed a significant increase in the expression of miRNA-210 and a significant reduction in the water content of brain tissue (P<0.05). The results of hematoxylin and eosin staining suggested that the miRNA-210 expression inhibition HI group showed marked edema, and the miRNA-210 overexpression HI group showed a significant improvement in edema.

CONCLUSIONSNeonatal rats show down-regulated expression of miRNA-210 after HI, suggesting that miRNA-210 may be involved in the development and progression of hypoxic-ischemic brain edema in neonatal rats.

Animals ; Animals, Newborn ; Brain Edema ; etiology ; Female ; Hypoxia-Ischemia, Brain ; etiology ; Male ; MicroRNAs ; analysis ; physiology ; Rats ; Rats, Sprague-Dawley

Adult ; Aged ; Bevacizumab ; therapeutic use ; Brain Neoplasms ; drug therapy ; therapy ; Edema ; drug therapy ; etiology ; Female ; Humans ; Male ; Middle Aged ; Re-Irradiation ; adverse effects

OBJECTIVETo investigate the clinical application, indication, timing and prognosis of blood purification (artificial liver, BP) in treatment of acute liver failure in children.

METHODArtificial liver was used to treat 30 cases of pediatric acute liver failure (PALF), who were hospitalized in pediatric intensive care unit of Bayi Children's Hospital Affiliated to Beijing Military Command General Hospital, during March 2010 to July 2013. Simple plasma exchange (PE) mode was used for PALF without complications, while PE combined with continuous veno-venous hemodiafiltration (CVVHDF) mode was used for PALF with cerebral edema and/or hepatorenal syndrome and/or serious abnormality of electrolyte and acid-base balance.

RESULTSixteen cases survived and restored hepatic function, with a survival rate of 53.3%. Single PE therapy could significantly decrease total bilirubin (TBIL) from (293.96 ± 214.52) µmol/L to (155.64 ± 140.97) µmol/L (P = 0.033), increase prothrombin time activity (PTA) from (34.50 ± 18.34) % to (60.50 ± 33.97) % (P = 0.013), while it did not significantly influence ammonia from (156.43 ± 67.23) µmol/L to (124.03 ± 62.58) µmol/L (P = 0.156) and alanine transarninase (ALT) from (752.53 ± 1 291.84) U/L to (132.00 ± 98.57) U/L (P = 0.066). PE + CVVHDF therapy could significantly ameliorate TBIL from (326.90 ± 233.85) µmol/L to (157.53 ± 125.31) µmol/L (P = 0.033), ALT from (1 476.64 ± 1 728.18) U/L to (169.38 ± 207.18) U/L (P = 0.019), ammonia from (215.83 ± 83.92) µmol/L to (141.25 ± 63.09) µmol/L (P = 0.022) and PTA from (36.68 ± 23.13)% to (71.75 ± 50.50) % (P = 0.044). Prothrombin time (PT) from (29.71 ± 17.75)s to (16.27 ± 6.38)s (P = 0.008) , ALT from (1 574.11 ± 1 775.96) U/L to (145.81 ± 113.89 ) U/L (P = 0.003) , TBIL from (233.16 ± 219.70) µmol/L to (75.19 ± 86.07) µmol/L (P = 0.012) , ammonia from (182.75 ± 90.07) µmol/L to (101.81 ± 37.14) µmol/L (P = 0.002) and PTA from (38.38 ± 20.39)% to (83.13 ± 41.68)% (P = 0.001) in survived cases significantly ameliorated after BP therapy. TBIL from (394.04 ± 192.80) µmol/L to (249.34 ± 113.97) µmol/L (P = 0.023) in died cases declined significantly after BP therapy, while alteration of PT, ALT, ammonia , and PTA had no statistical significance (P > 0.10) after BP therapy.

CONCLUSIONPE + CVVHDF therapy could significantly ameliorate not only TBIL and PTA but also ammonia and ALT compared with single PE therapy. The decline of only an index like TBIL or ALT after BP therapy could not improve the prognosis. The inconsistency between serum bilirubin and ALT levels was an important factor that suggested poor prognosis of ALF, and it might increase survival rate to use BP therapy before that inconsistency emerged.

Adolescent ; Bilirubin ; blood ; Biomarkers ; blood ; Brain Edema ; etiology ; therapy ; Child ; Child, Preschool ; Female ; Hemodiafiltration ; methods ; Heparin ; pharmacology ; Hepatorenal Syndrome ; etiology ; therapy ; Humans ; Infant ; Liver Failure, Acute ; blood ; complications ; mortality ; therapy ; Liver Function Tests ; Male ; Plasma Exchange ; Prothrombin Time ; Survival Rate ; Treatment Outcome

OBJECTIVETo observe the effect of Xingnaojing Injection combined with minimally invasive percutaneous drainage on brain edema and content of serum aquaporin-4 (AQP4) in patients with moderate hypertensive basal ganglia hemorrhage, and discuss the treatment mechanism of Xingnaojing injection combined with minimally invasive percutaneous drainage for cerebral hemorrhage.

METHODForty-two patients with moderate (25-50 mL) hypertensive basal ganglia hemorrhage (< 24 h) were selected and randomly divided into two groups: the observation group (n = 22) and the control group (n = 20). The neurological severity score were evaluated by the NIHSS (national institutes of health stroke scale), the volume of brain edemas were measured by head CT, the serum levels of AQP4 were determined by ELISA method on admission and 1 and 2 weeks after treatment.

RESULTOn admission, there was no significant difference in the scores of NIHSS, the volume of brain edemas and the level of serum AQP4 between the observation group and the control group. At the end of the first week after the treatment, the score of NIHSS of the observation group were lower than that of the control group, with significant different (P < 0.05); the observation group showed reduced volume of brain edemas than that on admission (P < 0.05), whereas the control group the control group showed increased volume of brain edemas than that on admission; the control group displayed increased level of serum AQP4 than that on admission, but without significant difference; the observation group displayed decreased level of serum AQP4 than that on admission (P < 0.05). At the end of the second week after the treatment, the control group showed decreased score of NIHSS than that on admission and at the end of the first week after treatment (P < 0.05). Compared with the control group, the observation group showed a much lower score of NIHSS (P < 0.01), the control group displayed reduced volume of brain edemas than that on admission and at the end of the first week after treatment, but the observation group was even lower than the control group. Both of observation and control groups displayed significantly reduced level of AQP4 (P < 0.05), but the observation group showed a lower AQP4 level than that of the control group (P < 0.05).

CONCLUSIONThe therapy of Xingnaojing injection combined with minimally invasive percutaneous drainage could remarkably reduce brain edema, and promote neural functional recovery, thus could be selected as a therapeutic regimen for patients with moderate hypertensive basal ganglia hemorrhage.

Aged ; Aquaporin 4 ; blood ; genetics ; Basal Ganglia Hemorrhage ; blood ; drug therapy ; etiology ; surgery ; Brain Edema ; blood ; drug therapy ; etiology ; surgery ; Drainage ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Hypertension ; complications ; Male ; Middle Aged ; Treatment Outcome

OBJECTIVETo investigate the protective effects of Jiedu Tongluo injection on cerebral edema induced by focal lesion of cerebral ischemia/reperfusion, the hydrous content of brain and the expressions of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin and MMP-9 in rats.

METHODThe model of brain middle cerebral artery ischemia/reperfusion was established by the thread approach. After 24 hours of reperfusion, cerebral edema formation was determined by the hydrous content of brain. The permeability of blood brain barrier was evaluated based on the leakage of Evans blue. Enzyme-linked immunoadsordent assay (ELISA)was used to examine the expression of ICAM-1, VCAM-1, E-selectin. The expression of MMP-9 was measured by immunohistochemistry.

RESULTJDTL, in the dose of 2 mL x kg(-1) and 4 mL x kg(-1), relieved cerebral edema (P < 0.05, P < 0.01), reduced the expressions of ICAM-1, VCAM-land E-selectin and decreased MMP-9 activity (P < 0. 05, P < 0.01) in model rats.

CONCLUSIONJiedu Tongluo injection has a protective effect on rat brain from cerebral edema induced by the injury of focal cerebral ischemia/reperfusion. The mechanism is related to that Jiedu Tongluo injection can reduce the expressions of ICAM-1, VCAM-1 and E-selectin and inhibit of MMP-9 activation in rat brain.

Animals ; Blood-Brain Barrier ; drug effects ; metabolism ; Brain Edema ; etiology ; metabolism ; prevention & control ; Brain Ischemia ; complications ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; E-Selectin ; metabolism ; Evans Blue ; metabolism ; Gene Expression Regulation, Enzymologic ; drug effects ; Injections ; Intercellular Adhesion Molecule-1 ; metabolism ; Male ; Matrix Metalloproteinase 9 ; metabolism ; Permeability ; drug effects ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; complications ; Vascular Cell Adhesion Molecule-1 ; metabolism

This study aimed to investigate inflammatory edema after cerebral ischemia through 7.0T MRI and proton magnetic resonance spectroscopy (MRS). All SD rats were randomly divided into sham operated group and middle cerebral artery occlusion (MCAO)-1 day, -3 day and -7 day groups. MRI scan of the brain was performed on a 7.0 Tesla MRI scanner. The volume of positive signals in the ischemic side was detected by using a T2 weighted spinecho multislice sequence; the changes in the height of water-peak were measured with point resolved spectroscopy (PRESS) sequences; cortical edema was detected by using wet-dry weight method; the degrees of nerve injury were evaluated by Bederson neurological score system; double-labeling immunofluorescence technique was used to explore the molecular mechanisms of post-ischemia cerebral edema. The results showed that high T2WI signals were observed in MCAO-1 day, -3 day and -7 day groups, and the water-peak height and water-peak area of MCAO groups were higher than those of sham operated group (P<0.05). Neurological score results were consistent with the degree of brain edema, and a large number of microglia accumulated in the ischemic cortex. Our results suggested that non-invasive MRI technology with the advantage of high spatial resolution and tissue resolution can comprehensively and dynamically observe inflammatory edema after cerebral ischemia from a three-dimensional space, and contribute to evaluation and treatments in clinic.
Animals ; Brain ; diagnostic imaging ; pathology ; Brain Edema ; diagnostic imaging ; etiology ; Brain Ischemia ; complications ; CD11b Antigen ; metabolism ; Immunohistochemistry ; Infarction, Middle Cerebral Artery ; complications ; Inflammation ; diagnostic imaging ; etiology ; Magnetic Resonance Imaging ; methods ; Magnetic Resonance Spectroscopy ; Male ; Microglia ; metabolism ; Microscopy, Confocal ; Microscopy, Fluorescence ; Radiography ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Time Factors