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Aim To explore the effect of camellia nitidissima polysaccharides (CNP) on acute intracerebral hemorrhage (ICH) and its mechanism related to regulation of microglia polarization. Method Adult male C57 BIV6 mice were randomly divided into sham-oprated control group, ICH group and CNP group. CNP was intragastrically administered immediately after intracerebral hemorrhagefor a consecutive three days. Neural functional outcomes were evaluated by neurological deficiency score (NDS) , open field test, and adhesive removal test. Blood-brain barrier destruction and pathological injury were detected by Evans blue staining and brain water content. Inflammatory factors were detected by ELISA. Microglia phenotypic status was evaluated and determined by quantitative real-time polymerase chain reaction ( qPCR) analyses, and immunofluorescence labeling. Results CNP significantly reduced neurological deficit scores and ameliorated cerebral edema and blood-brain barrier injury three days after ICH. Also, CNP treatment improved signifi-cantly motor function three days after ICH. In addition, CNP decreased proinflammatory mediators and inhibited the activation of microglia. Furthermore, treatment of CNP decreased microglia Ml markers and increased M2 markers. Conclusion CNP attenuates acute intracerebral hemorrhage thrdugh skewing microglia toward a more anti-inflammatory property.
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Clinical advances in the treatment of intracranial hemorrhage (ICH) are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury. Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases. Our results indicated a significant increase in the level of acrolein after ICH in mouse brain. In primary neurons, acrolein induced an increase in mitochondrial fragmentation, loss of mitochondrial membrane potential, generation of reactive oxidative species, and release of mitochondrial cytochrome c. Mechanistically, acrolein facilitated the translocation of dynamin-related protein1 (Drp1) from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission. Further studies found that treatment with hydralazine (an acrolein scavenger) significantly reversed Drp1 translocation and the morphological damage of mitochondria after ICH. In parallel, the neural apoptosis, brain edema, and neurological functional deficits induced by ICH were also remarkably alleviated. In conclusion, our results identify acrolein as an important contributor to the secondary brain injury following ICH. Meanwhile, we uncovered a novel mechanism by which Drp1-mediated mitochondrial oxidative damage is involved in acrolein-induced brain injury.
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Clinical advances in the treatment of intracranial hemorrhage (ICH) are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury. Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases. Our results indicated a significant increase in the level of acrolein after ICH in mouse brain. In primary neurons, acrolein induced an increase in mitochondrial fragmentation, loss of mitochondrial membrane potential, generation of reactive oxidative species, and release of mitochondrial cytochrome c. Mechanistically, acrolein facilitated the translocation of dynamin-related protein1 (Drp1) from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission. Further studies found that treatment with hydralazine (an acrolein scavenger) significantly reversed Drp1 translocation and the morphological damage of mitochondria after ICH. In parallel, the neural apoptosis, brain edema, and neurological functional deficits induced by ICH were also remarkably alleviated. In conclusion, our results identify acrolein as an important contributor to the secondary brain injury following ICH. Meanwhile, we uncovered a novel mechanism by which Drp1-mediated mitochondrial oxidative damage is involved in acrolein-induced brain injury.
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Objective To investigate the effect of procyanidins on cerebral edema and inflammation of secondary brain injury after intracerebral hemorrhage.Methods Forty-eight C57BL6 mice were randomly divided into 4 groups:sham-operation+ saline group,sham-operation + procyanidins (100 mg/kg) group,intracerebral hemorrhage (ICH) + saline group and ICH + procyanidins (100 mg/kg) group.The Bederson method was used to detect postoperative nerve function score in mice.The brain tissue water content was measured by wet-dry weight method.The variety of morphological in brain tissue was observed by hematoxylin-eosin (HE) staining.The expression of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1(Iba-1) in mouse brain tissue were observed by western blot.The apoptosis of brain tissue was observed by TUNEL and western blot method.Results Compared with the ICH+saline group after 12h,the nerve function score in the ICH + proanthocyanidins group was significantly decreased (P＜0.05),and the water content of brain tissue was also significantly decreased (P＜0.05).The HE staining results showed that procyanidins decreased the number of neurocytes lesions in cerebral hemorrhage mice and reduced the amount of brain tissue hemorrhage.Western blot results showed that procyanidins promoted the expression of Bcl-2,decreased the expression of Bax,Caspase3,GFAP and Iba-1 in cerebral hemorrhage mice.The TUNEL results showed that procyanidins could inhibit the apoptosis of brain tissue neurons in mouse with intracerebral hemorrhage.Conclusion Procyanidins inhibits the production of neurotoxic substances possibly by reducing the expression of GFAP and Iba-1,and prevents and treats secondary brain injury after intracerebral hemorrhage.
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Objective To evaluate the effect of mild hypothermia combined with hypbaric oxygen (HBO) treatment on secondary brain injury in patients with severe craniocerebral injury.Methods A prospective study was conducted in this study.Forty-two patients with severe craniocerebral injury admitted to hospital within 8 hours were randomly divided into sub-hypothermia combined with HBO treatment group and conventional HBO control group,21 cases in either group.Cerebral hemorrhage and brain edema were calculated by reviewed head CT on the 1st day,15th day and 30th day after injury.GCS (Glasgow Coma Scale) score was calculated at the same time.The number of cases of cerebral infarction was counted in the two groups.GOS (Glasgow Outcome Score) prognosis was scored for both groups of patients six months after injury.Two groups of sample rates were compared using a chi-square test with continuous correction,The intergroup comparisons were analyzed by independent sample t test by using SPSS version 13.0 software.Differences were considered statistically significant if P ＜ 0.05.Results (1) The amount of cerebral hemorrhage and edema in the treatment group were significantly lower than those in the control group on the 15th day and 30th day after injury [(21.71 ±4.3) vs.(26.33 ±5.23);(14.33 ± 1.93) vs.(16.86 ±2.86),P ＜0.05].(2) The GCS score of the treatment group was higher than that of the control group on the 15th day and 30th day after injury [(4.62 ±0.49) vs.(2.49 ±0.56);(9.76 ± 1.37) vs.(8.57 ± 0.92),P ＜ 0.05];(3) There were 2 cases of traumatic cerebral infarction in the treatment group and 9 cases in the control group (x2 =4.434,P =0.035).The GOS score in the treatment group was higher than that in the control group six months after injury [(4.29 ± 0.84) vs.(3.38 ± 0.74),P =0.001].Conclusions Mild hypothermia combined with hyperbaric oxygen treatment can reduce the secondary brain injury and improve the prognosis of patients with severe craniocerebral injury.It is worth further study,the mechanism of hypothermia remains to be further studied.
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Objective To investigate the effects of [Gly14]-Humanin(HNG) on SOD, MDA, GSH and cell apopto?sis in a rat model of secondary brain injury. Methods One hundred thirty-five adult and healthy male rats were random?ly divided into 3 groups: sham model group (n=45), vehicle control group (n=45) and HNG group (n=45). Secondary brain injury was induced in the vehicle control and HNG groups using improved Feeney method. Vehicle control received abdominal injections of Sodium Chloride Injection (2 ml/kg) whereas the HNG group received abdominal injections of HNG (2 μL/kg) immediately and 24 h after injury. Each group was divided into three subgroups (n=15 rats per each group) by sacrificed time including 1 h, 3 d, and 7 d after injury. The expression levels of SOD, MDA and GSH of the brain tissue were analyzed and the cell apoptosis was examined using TUNEL method after brain contusion. Results MDA and cell apoptosis around the lesion started to increased at 1h, reached a peak at 3d and then gradually subsided but still remained a higher level at 7 d than 1 h. HNG significantly attenuated brain injury-induced increase in MDA and apopto?sis at all time points (P<0.05). By contrast, SOD started to decrease at 1h, reached the lowest point at 3 d and then gradu? ally recovered but still remained a lower level at 7 d than 1 h. HNG significantly mitigated brain injury-induced increase in MDA and apoptosis at all time points (P<0.05). The time course of GSH expression followed a pattern similar to that of MDA. MDA expression was strongly positive correlated with the number of cell apoptosis (r=0.720, P<0.05), strongly neg?ative correlated with the level of SOD and GSH(r=-0.702, P<0.05;r=-0.674, P<0.05). Conclusions After brain injury, HNG inhibits oxidative stress levels and reduces apoptosis, thereby mitigating secondary brain injury.
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Objective To study the clinical significance of early changes in cerebral oxygen and glucose metabolism in patients with cerebral hemorrhage and with Glasgow coma score (GCS) of 5-8 caused by acute hypertension in order to find relationship between those changes and prognosis.Methods From January 1,2011 to June 30,2012,a cohort of 43 patients with cerebral hemorrhage caused by acute hypertension were enrolled for retrospective study.Radial artery and internal jugular vein were separately cannulated retrogradely for collecting blood for blood gas analysis and blood glucose tests carried out 24 hours after the onset of the cerebral hemorrhage and then every 6-8 hours and as any major changes in physical signs of patients occurred.And this monitoring kept for consecutive 3 days.The data of these laboratory findings were analyzed and calculated to determine internal jugular vein oxygen saturation (SjVO2),cerebral oxygen utilization rate (CEO2),cerebral arterio-venous oxygen difference (AVDO2),arterio-venous blood glucose difference (V-Aglu),arterio-venous lactic acid difference (V-Alac) and absolute value of carbon dioxide pressure difference between jugular vein and artery (V-APCO2).All patients met the diagnostic criteria of hypertensive cerebral hemorrhage revised by the 4th National Academic Conference on cerebrovascular disease in 1995 requiring diagnosis confirmed by brain CT,admitted within 24 hours of onset,Glasgow coma score (GCS) 5-8 and a history of hypertension.Exclusion criteria were:cerebral hemorrhage caused by traumatic intracranial hematoma,spontaneous subarachnoid hemorrhage,arteriovenous malformation and Moyamoya disease,intracranial tumor apoplexy,cerebral bleeding derived from the disturbance of blood coagulation system,and cerebral hemorrhagic infarction.According to the short-term prognosis,the patients were divided into the death group and the survival group.Then the differences in biomarkers mentioned above between two groups were compared to find the relationship between levels of those biomarkers and outcomes of patients.Thereafter,the results of this retrospective study inspired us to carry out a prospective and double blind study in another 23 patients from July 2012 to January 2013 for further confirming the validity of these biomarkers to predict the short-term outcomes of patients.The statistical analysis was performed with SPSS 16.0 software (SPSS,USA) and a P ＜ 0.05 was considered significant.Numerical values were given as means ± SD unless stated otherwise.For statistical analyses,normality was assessed before choosing the relevant comparative test and nonparametric tests was used in cases as the normality test failed.Results Of 43 patients with cerebral hemorrhage for retrospective analysis,there were 27 male and 16 female with M/F ratio =1.7:1,aged from 49 to 81 with mean 66.2 ± 15.3 years and their GCS scores were 5-8.of them,there were 28 patients suffered from basal ganglia hemorrhage,6 cerebella hemorrhage,5 pons cerebelli hemorrhage and 4 lobe hemorrhage.There were 25 patients with supratentorial hematoma in volume of no less than 30 mL and 10 infratentorial hematoma in volume of no less than 10 mL of them,11 patients were treated with craniotomy and evacuation of hematoma or decompression craniotomy and rest were treated with conservative strategy.Compared with the death group,the CEO2,AVDO2,V-AGlu,V-ALac in the survival group decreased significantly (P ＜ 0.05),while V-APCO2 and SjvO2 increased significantly (P ＜ 0.05).In the subsequent prospective study,the accuracy rate of the levels of SjvO2 ＜ 52％,AVDO2 ＞ 83％ for predicting prognosis was 78.3％.Conclusions The cerebral oxygen and glucose metabolism was obviously abnormal in hypertensive cerebral hemorrhagic patients with GCS score of 5-8 among the death group,and especially the anaerobic metabolism was apparently increased.It was also found that the risk threshold (SjvO2 ＜ 52％,AVDO2 ＞83％) was in close relationship with patients'death expectation.
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Traumatic brain injury is the main cause of death and disability in the young population, which presumes a large number of years of potential life lost and a great economic impact. Vital and functional outcomes after suffering a traumatic brain injury depend both on the severity of the initial biomechanical impact (primary injury) and on the presence and the severity of systemic or intracranial insults that magnify and/or produce new brain injuries, the so-called secondary injuries. Currently, no treatment in effective in improving functional recovery, except for usual medical care. Therefore, the main purpose of the care provided to a patient with severe cranial trauma is based on preventing and treating secondary brain injuries by maintaining an adequate cerebral perfusion and oxygenation. Increased intracranial pressure is associated with mortality and with unfavorable functional outcomes is patients with severe traumatic brain injury. The main clinical practice guidelines recommend using a number of staggered therapeutic measures. However, although these measures seem to be efficient in reducing intracranial pressure, this effect is not often translated into clinical improvement. This review describes the essential principles of the management of patients with severe traumatic brain injury in intensive care units.
Subject(s)
Humans , Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/drug therapy , Brain Injuries, Traumatic/therapy , Seizures/prevention & control , Intracranial Hypertension , Neuromuscular Blockade , Neurophysiological Monitoring , Tomography, X-Ray ComputedABSTRACT
Objective To investigate the dynamic changes of interleukin-1 receptor-associated kinases (IRAK-4) in hypoxic neurons and explore their role in regulation of inflammatory reaction. Methods The B35 cells exposed to hypoxia of 3% O2,5% CO2 and 92% N2 were cultured for 1,3,6, 12,24,48,72 and 96 hours respectively. Then, mRNA and protein expressions of IRAK-4 were detected by RT-PCR and Western blot, the expression of IRAK-4 in the cells were observed by laser scanning con-focal microscope (LSCM), and the concentration of IL-6 was measured by ELISA method. Results After hypoxia, the mRNA and protein expressions of IRAK-4 were increased at one hour, reached the peak at six hours (P<0.05), kept at a high level at 12 hours (P<0.05) , but decreased gradually to the normal oxygen level at 24 hours (P < 0.05) and to below the normal oxygen level at 48 hours (P < 0.05). Immunofluorescence results showed that the fluorescence intensity of IRAK-4 was gradually increased with time. The changes of IL-6 in the supernatant were positively correlated with protein expression of IRAK-4 (r =0.84, P < 0.05 ). Conclusions Hypoxia can increase the expression of IRAK-4 at transcription and translation levels in a certain period of time, which may participate in down-stream inflammatory reaction and lead to increase of IL-6 expression.
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Objective To explore the mechanism of the microglia inflammatory response through observing the changes of interleukin-1 receptor associated kinase-4(IRAK-4) expression in murine N9 microglia cells under hypoxia.Methods N9 cells were exposed to 3%O2,5%CO2,92%N2 for 1,3,6,12 and 24 h respectively.The IRAK-4 protein level was detected by Western blotting and the celluar change was observed by laser scanning confocal microscope(LSCM).The TNF-? level was measured by ELISA.Results After hypoxia,the expression of IRAK-4 protein was increased in a time-dependent manner.The elevation began at 1 h after hypoxia,increased significantly at 3 h(P0.05).The fluorescence intensity of IRAK-4 also increased with the extension of anoxic time.The TNF-? level change were similar.There were significant positive correlations between the expression of IRAK-4 and TNF-?(P