Alteration of microRNA expression in cerebrospinal fluid of unconscious patients after traumatic brain injury and a bioinformatic analysis of related single nucleotide polymorphisms / 中华创伤杂志(英文版)

<p><b>PURPOSE</b>It is becoming increasingly clear that genetic factors play a role in traumatic brain injury (TBI), whether in modifying clinical outcome after TBI or determining susceptibility to it. MicroRNAs are small RNA molecules involved in various pathophysiological processes by repressing target genes at the post- transcriptional level, and TBI alters microRNA expression levels in the hippocampus and cortex. This study was designed to detect differentially expressed microRNAs in the cerebrospinal fluid (CSF) of TBI patients remaining unconscious two weeks after initial injury and to explore related single nucleotide polymorphisms (SNPs).</p><p><b>METHODS</b>We used a microarray platform to detect differential microRNA expression levels in CSF samples from patients with post-traumatic coma compared with samples from controls. A bioinformatic scan was performed covering microRNA gene promoter regions to identify potential functional SNPs.</p><p><b>RESULTS</b>Totally 26 coma patients and 21 controls were included in this study, with similar distribution of age and gender between the two groups. Microarray showed that fourteen microRNAs were differentially expressed, ten at higher and four at lower expression levels in CSF of traumatic coma patients compared with controls (p<0.05). One SNP (rs11851174 allele: C/T) was identified in the motif area of the microRNA hsa-miR-431-3P gene promoter region.</p><p><b>CONCLUSION</b>The altered microRNA expression levels in CSF after brain injury together with SNP identified within the microRNA gene promoter area provide a new perspective on the mechanism of impaired consciousness after TBI. Further studies are needed to explore the association between the specific microRNAs and their related SNPs with post-traumatic unconsciousness.</p>

Improved neurite outgrowth on central nervous system myelin substrate by siRNA-mediated knockdown of Nogo receptor / 中华创伤杂志(英文版)

<p><b>PURPOSE</b>To investigate the in vitro effect of short interfering RNAs (siRNAs) against Nogo receptor (NgR) on neurite outgrowth under an inhibitory substrate of central nervous system (CNS) myelin.</p><p><b>METHODS</b>Three siRNA sequences against NgR were designed and transfected into cerebellar granule cells (CGCs) to screen for the most effcient sequence of NgR siRNA by using reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence staining. NgR siRNA sequence 1 was found the most efficient which was then transfected into the CGCs grown on CNS myelin substrate to observe its disinhibition for neurite outgrowth.</p><p><b>RESULTS</b>Compared with the scrambled control sequence of siRNA, the NgR siRNA sequence 1 significantly decreased NgR mRNA level at 24 h and 48 h (p <0.05), which was recovered by 96 h after transfection. NgR immunoreactivity was also markedly reduced at 24 and 48 h after the transfection of siRNA sequence 1 compared with that before transfection (p<0.05). The NgR immunoreactivity was recovered after 72 h post-transfection. Moreover, the neurite outgrowth on the myelin substrate was greatly improved within 72 h after the transfection with siRNA sequence 1 compared with the scrambled sequence-transfected group or non-transfected group (p<0.05).</p><p><b>CONCLUSION</b>siRNA-mediated knockdown of NgR expression contributes to neurite outgrowth in vitro.</p>

Is management of acute traumatic brain injury effective? A literature review of published Cochrane Systematic Reviews / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate all the possible therapeutic measures concerning the acute management of traumatic brain injury (TBI) mentioned in Cochrane Systematic Reviews published in the Cochrane Database of Systematic Reviews (CDSR).</p><p><b>METHODS</b>An exhausted literature search for all published Cochrane Systematic Reviews discussing therapeutic rather than prevention or rehabilitative interventions of TBI was conducted. We retrieved such databases as CDSR and Cochrane Injury Group, excluded the duplications, and eventually obtained 20 results, which stand for critical appraisal for as many as 20 different measures for TBI patients. The important data of each systematic review, including total population, intervention, outcome, etc, were collected and presented in a designed table. Besides, we also tried to find out the possible weakness of these clinical trials included in each review.</p><p><b>RESULTS</b>Analysis of these reviews yielded meanfuling observations: (1) The effectiveness of most ordinary treatments in TBI is inconclusive except that corticosteroids are likely to be ineffective or harmful, and tranexamic acid, nimodipine and progesterone show a promising effect in bleeding trauma, traumatic subarachnoid hemorrhage, TBI or severe TBI. (2) A majority of the systematic reviews include a small number of clinical trials and the modest numbers of patients, largely due to the uncertainty of the effectiveness. (3) The quality of most trials reported in the systematic reviews is more or less questionable. (4) In addition, lots of other complex factors together may lead to the inconclusive results demonstrated in the Cochrane Systematic Reviews.</p><p><b>CONCLUSIONS</b>For clinical physicians, to translate these conclusions into practice with caution is essential. Basic medication and nursing care deserve additional attention as well and can be beneficial. For researchers, high quality trials with perfect design and comprehensive consideration of various factors are urgently required.</p>

Application of hydrogen proton magnetic resonance spectroscopy in diagnosis of peripheral tumor cell infiltration of gliomas / 上海第二医科大学学报

Objective To explore the application of hydrogen proton magnetic resonance spectroscopy (1H-MRS) in the diagnosis of peripheral tumor cell infiltration of gliomas. Methods Forty patients with glioma were examined by 1H-MRS preoperation, and were divided into low grade glioma group (n=20) and high grade glioma group (n=20) according to postoperative pathological diagnosis. Tumor resection with peripheral tissues marked previously was carried out under the guidance of neuronavigator system. All the pathological sections were divided into positive group and negative group according to the presence or absence of tumor cells, and the differences in pathological findings of peripheral regions (region 1, 2 and 3) and 1H-MRS values were analyzed in these two groups. Results No infiltration was found in the peripheral regions of low grade glioma group except for one case in peripheral region 1, while infiltration was found in all peripheral regions of high grade glioma group. There was no significant difference in 1H-MRS values between positive group (n=24) and negative group (n=36) in patients with high grade glioma (P>0.05). Conclusion 1H-MRS enjoys some advantages over routine radiological examinations in the diagnosis of peripheral tumor cell infiltration of gliomas. Total removal can be expected when combined with neuronavigator system, while there is room for improvement for relevant techniques.

Effect of resuscitation after selective cerebral ultraprofound hypothermia on expressions of nerve growth factor and glial cell line-derived neurotrophic factor in the brain of monkey / 神经科学通报·英文版

<p><b>OBJECTIVE</b>To investigate the expression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) in monkeys of resuscitation after selective cerebral ultraprofound hypothermia and blood flow occlusion.</p><p><b>METHODS</b>The monkeys were immediately removed brain after death in operation of group A (identical temperature perfusion group) and group B (ultraprofound hypothermia perfusion group). Immunohistochemical technique was used to determine frontal cellular expression of NGF and GDNF. Statistics were analyzed by ANOVA analyses with significance level at P < 0.05.</p><p><b>RESULTS</b>The expressions of NGF and GDNF in the group B were significantly higher than those in the group A (P < 0.05).</p><p><b>CONCLUSION</b>NGF and GDNF increased significantly in the monkeys of resuscitation after selective cerebral ultraprofound hypothermia and blood flow occlusion. It may be a protective mechanism for neuron survival and neural function recovery.</p>

Establishment of maca mulatta model of resuscitation after selective cerebral ultra-deep hypothermic blood flow occlusion / 中华外科杂志

<p><b>OBJECTIVE</b>To study the feasibility of resuscitation after selective cerebral ultra-deep hypothermia and blood flow occlusion.</p><p><b>METHODS</b>Ten 4-10 year-old maca mulattas were divided into 3 groups: four-vessel occlusion group, two-vessel occlusion group and identical temperature perfusion group. MRI were examinated before and after operation, the vital signs and the hemodynamical parameters were observed during the experiment, neurological deficient evaluation was performed after operation.</p><p><b>RESULTS</b>In all of the ten monkeys, the hemodynamical parameters of two-vessel occulation were steady during the operation, and all of them lived after filling 60 minutes. MRI were normal after operation, and the function of neurological deficient scale was normal. The others of identical temperature perfusion group and four-vessel occlusion group were not resuscitation after filling 60 minutes and died.</p><p><b>CONCLUSION</b>Monkey could resuscitate from selective cerebral ultra-deep hypothermia and blood flow occlusion of bilateral common carotid artery in 60 minutes.</p>

Effect of arousal methods for 175 cases of prolonged coma after severe traumatic brain injury and its related factors / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To determine the effect of arousal methods for prolonged coma of 175 patients with severe traumatic brain injury and related factors.</p><p><b>METHODS</b>There were 175 cases with persistent coma longer than 1 month after severe traumatic brain injury. Coma lasted 1-12 months. Arousal procedures included hyperbaric oxygen, physical therapy and arousal drugs.</p><p><b>RESULTS</b>In the 175 prolonged coma patients 110 got recovery of consciousness; in 118 cases with coma of 1-3 months, 86 cases recovered consciousness (72.9%); in 42 cases with coma of 4-6 months, 20 cases recovered consciousness (47.6); and in 15 cases with coma of longer than 6 months, only 4 cases recovered consciousness (26.7%). The recovery of consciousness depended on patient's primary brain stem damage, cerebral hernia, GCS score, and age.</p><p><b>CONCLUSIONS</b>Application of appropriate arousal procedures improves recovery of consciousness in patients with prolonged coma.</p>

Effects on neuronal ultrastructure and nervous system of monkey after selective cerebral profound hypothermia and blood flow occlusion / 中华外科杂志

<p><b>OBJECTIVE</b>To study the effects of deep hypothermia on the neuronal ultrastructure and nervous system of monkey after selective cerebral profound hypothermia and blood flow occlusion.</p><p><b>METHODS</b>Brain-local extracorporeal circulation was established by right internal carotid artery deep hypothermic perfusion and homolateral external jugular vein backflow, brain blood flow was recovered from circulatory arrest 60 - 80 minutes late and monkey came back naturally.</p><p><b>RESULTS</b>In all 7 monkeys, 5 were succeeded in being build up the models except for 2 because of technic problems, and 4 of them lived up for ever. The function of nervous system grade, essential organ and neuronal ultrastructure were normal.</p><p><b>CONCLUSION</b>Selective cerebral profound hypothermia can increase the ability of brain to endure hypovolemia and hypoxidosis and prolong the time of blood flow occlusion.</p>

Neuroprotective effects of AM-36 on traumatic brain injury induced by fluid percussion in rats / 中华创伤杂志

Objective To investigate neuroprotective effect of AM-36 on secondary brain injury following traumatic brain injury(TBI)in rats.Methods A total of 38 male Sprague-Dawley rats were divided into an experimental group,a control group and a sham operation group,then sustained to moder- ate TBI.AM-36(0.1 ml/100 g)was administered intraperitoneally in the experimental group and isoton- ic saline solution was administered intraperitoneally in the control and the sham operation groups at 30 mi- nutes,24 and 48 hours after TBI,respectively.The brain water content was determined at 24 hours after TBI.Rats were sacrificed by decapitation at 24 hours or one week after TBI for observing histological changes in peripheral cortex,thalamus and hippocampus by means of Hematoxylin and Eosin staining and Fluoro-Jade(F-J)staining.Results The brain water content of bilateral hemispheres 24 hours after TBI in the experimental group was significantly decreased,compared to that of the control group.Histo- logical examination revealed less degenerating neurons(F-J positive neurons)in the cortex,thalamus, CAI and CA3 of the hippocampus in AM-36 treated rats 24 hours and one week after injury(P＜0.05). Conclusion Systemic administration of AM-36 at the early stage after TBI can decrease brain water content and exert neuroprotective effect on TBI.F-J staining can be used for histopathologic quantitation of neuronal damage,for it can accurately exhibit pathologic changes following TBI induced by fluid per- cussion.

The prospective study of the relationship between perimesencephalic cistern of CT scanning and the outcome of the patients with acute craniocerebral injury / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To explore prospectively the relationship between the state of perimesencephalic cistern and the degree of deformation of the midbrain on CT scanning and the outcome of the patients with acute craniocerebral injury.</p><p><b>METHODS</b>The CT scan features including the states of perimesencephalic cisterns, the deformations of the midbrain and the ratios of the occipitofrontal diameter and the transverse diameter of the midbrain of 132 cases were measured. The GOS of the patients 3 months after trauma were regarded as outcome.</p><p><b>RESULTS</b>The rate of unfavorable outcome (dead, vegetative status, severe disability) was significantly correlated with perimesencephalic cistern narrower than 1 mm (P<0.05), especially narrower than 0.5 mm (P<0.005), deformed midbrain (P<0.005) or abnormal ratio (<0.9 or >1.1) of the occipitofrontal diameter and transverse diameter of the midbrain (P<0.01). But the patient's perimesencephalic cistern wider than 1mm and the patients without deformed midbrain got favorable outcome (moderate disability/good recovery).</p><p><b>CONCLUSIONS</b>The state of the compressed perimesencephalic cistern (<1 mm) and the deformation of the midbrain may significantly indicate unfavorable outcome of the patients with acute craniocerebral injury.</p>

Standard large trauma craniotomy for severe traumatic brain injury / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To study the effect of standard large trauma craniotomy (SLTC) on outcomes of patients with severe traumatic brain injury (TBI) (GCS<=8).</p><p><b>METHODS</b>230 patients with severe TBI were randomly divided into two groups. 115 patients underwent SLTC (10 cm x 12 cm) as an SLTC group, and other 115 patients underwent temporo-parietal or fronto-temporal craniotomy (6 cm x 8 cm) according to the position of hematomas as a routine craniotomy (RC) group. Other treatments were identical in two groups. According to Glasgow outcome scale (GOS), the prognosis of the patients was evaluated and the complications were compared between two groups.</p><p><b>RESULTS</b>27 patients got good outcome and moderate disability (23.5%), 40 severe disability and vegetative survival (34.8%), and 48 died (41.7%) in SLTC group. 21 patients got good outcome and moderate disability (18.3%), 28 severe disability and vegetative survival (24.3%), and 66 died (57.4%) in RC group. The incidence of incision hernia was lower in SLTC group than in RC group. However, the incidence of operative encephalocele, traumatic epilepsy and intracranial infection were not different in two groups.</p><p><b>CONCLUSIONS</b>Standard large trauma craniotomy significantly reduces the mortality of patients with severe TBI without serious complications, but does not improve the life quality of the patients.</p>

Effects of ganglioside GM1 on reduction of brain edema and amelioration of cerebral metabolism after traumatic brain injury / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To observe the effects of ganglioside GM1 on reduction of brain edema and amelioration of cerebral metabolism after traumatic brain injury (TBI).</p><p><b>METHODS</b>An acute experimental closed TBI model in rats was induced by a fluid-percussion brain injury model. At five and sixty minutes after TBI, the animals were intraperitoneally injected by ganglioside GM1 (30 mg/kg) or the same volume of saline. At the 6th hour after TBI, effects of ganglioside GM1 or saline on changes of mean arterial pressure (MAP), contents of water, lactic acid (LA) and lipid peroxidation (LPO) in the injured cerebral tissues were observed.</p><p><b>RESULTS</b>After TBI, MAP decreased and contents of water, LA and LPO increased in brain injury group; however, MAP was back to normal levels and contents of water, LA and LPO decreased in ganglioside GM1 treated group, compared with those in brain injury group (P < 0.05). No significant difference between the saline treated group and the brain injury group (P > 0.05) was observed.</p><p><b>CONCLUSIONS</b>Ganglioside GM1 does have obvious neuroprotective effect on early TBI.</p>

The correlation between mRNA and protein expression of bax and bcl-xL follo wing fluid percussion brain injury in rats / 第二军医大学学报

Objective: To investigate the alterations of bcl-2 gene family in the rat brain and the molecular mechanism of neuronal apoptosis follow ing traumatic brain injury (TBI). Methods: Male Sprague-Dawley rats were subjected to lateral fluid percussion brain injury(FPBI) of moderate severity. bax and bcl-xL mRNA and protein expression was detected by RT-PCR an d immunohistochemistry. In addition to morphological evidence of apoptosis, TUNE L histochemistry was used to identify DNA fragmentation in situ under both l ight and electron microscope, whereas characteristic internucleosomal DN A fragm entation of apoptosis was demonstrated by DNA gel electrophoresis. Resul ts: bcl-xL mRNA and protein decreased in the ipsilateral hemisphere t o the impact site as early as 6 h post-injury［(67.42±7.54)% and (85.85±5.72)% r espectively］. The decrease in bcl-xL mRNA and protein preceded apoptosis was observed 12 h post-injury. And this was the main cause of up-regulation of the ratio of bax to bcl-xL in the acute period(minutes-hours) followin g FPBI. bax mRNA and protein were observed to rise slowly, doubled 3 d post- injury, returned to sham level slowly. The delayed cell death (days-weeks) migh t associated with the up-regulation of pro-apoptotic gene bax. Conclusio n: The expression of bcl-xL and bax coincide with apoptosis following TBI. The reg ulation of bax and bcl-xL by TBI occur before transcription. The balance of bax/bcl-xL ratio determines the neurocytes to survive or die following FPBI.

Alteration of Bcl-2, Bcl-x and Bax protein expression following fluid per cussion brain injury in rats / 第二军医大学学报

Objective: To investigate the alteration of bcl- 2 gene family in the rat brain and the molecular mechanism of neuronal apoptosis following traumatic brain injury. Methods: Male Sprague -Dawley rats were subjected to lateral fluid percussion brain injury(FPI) of mo derate severity. Bcl-2, Bcl-x and Bax protein expression was detected by immun ohistochemistry. Results: (1) The immunoreactivity of Bcl-2 and Bcl-x protein decreased in the hippocampus ipsilateral impact site as early as 6 h post-injury, and this was the main cause of down-regulation of the ratio of Bcl-2+Bcl-x to Bax. (2) During 1-3 d after injury, the Bax protein express i on increased significantly, while the Bcl-2 and Bcl-x protein expression decre ased relatively slow. The decreased ratio of Bcl-2+Bcl-x to Bax was mainly due to the Bax up-regulation. Conclusion: The bcl-2 gene family is involved in neuronal apoptosis after FBI, and the protein expression alteration of the family members leads the neuronal cell to apoptosis.

The correlation between mRNA and protein expression of bax and bcl-xL follo wing fluid percussion brain injury in rats / 第二军医大学学报

Objective: To investigate the alterations of bcl-2 gene family in the rat brain and the molecular mechanism of neuronal apoptosis follow ing traumatic brain injury (TBI). Methods: Male Sprague-Dawley rats were subjected to lateral fluid percussion brain injury(FPBI) of moderate severity. bax and bcl-xL mRNA and protein expression was detected by RT-PCR an d immunohistochemistry. In addition to morphological evidence of apoptosis, TUNE L histochemistry was used to identify DNA fragmentation in situ under both l ight and electron microscope, whereas characteristic internucleosomal DN A fragm entation of apoptosis was demonstrated by DNA gel electrophoresis. Resul ts: bcl-xL mRNA and protein decreased in the ipsilateral hemisphere t o the impact site as early as 6 h post-injury［(67.42±7.54)% and (85.85±5.72)% r espectively］. The decrease in bcl-xL mRNA and protein preceded apoptosis was observed 12 h post-injury. And this was the main cause of up-regulation of the ratio of bax to bcl-xL in the acute period(minutes-hours) followin g FPBI. bax mRNA and protein were observed to rise slowly, doubled 3 d post- injury, returned to sham level slowly. The delayed cell death (days-weeks) migh t associated with the up-regulation of pro-apoptotic gene bax. Conclusio n: The expression of bcl-xL and bax coincide with apoptosis following TBI. The reg ulation of bax and bcl-xL by TBI occur before transcription. The balance of bax/bcl-xL ratio determines the neurocytes to survive or die following FPBI.

Alteration of Bcl-2, Bcl-x and Bax protein expression following fluid per cussion brain injury in rats / 第二军医大学学报

Objective: To investigate the alteration of bcl- 2 gene family in the rat brain and the molecular mechanism of neuronal apoptosis following traumatic brain injury. Methods: Male Sprague -Dawley rats were subjected to lateral fluid percussion brain injury(FPI) of mo derate severity. Bcl-2, Bcl-x and Bax protein expression was detected by immun ohistochemistry. Results: (1) The immunoreactivity of Bcl-2 and Bcl-x protein decreased in the hippocampus ipsilateral impact site as early as 6 h post-injury, and this was the main cause of down-regulation of the ratio of Bcl-2+Bcl-x to Bax. (2) During 1-3 d after injury, the Bax protein express i on increased significantly, while the Bcl-2 and Bcl-x protein expression decre ased relatively slow. The decreased ratio of Bcl-2+Bcl-x to Bax was mainly due to the Bax up-regulation. Conclusion: The bcl-2 gene family is involved in neuronal apoptosis after FBI, and the protein expression alteration of the family members leads the neuronal cell to apoptosis.