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>