GRIK1 promotes glioblastoma malignancy and is a novel prognostic factor of poor prognosis

Primary tumors of the central nervous system(CNS)are classified into over 100 different histological types.The most common type of glioma is derived from astrocytes,and the most invasive glioblastoma(WHO IV)accounts for over 57%of these tumors.Glioblastoma(GBM)is the most common and fatal tumor of the CNS,with strong growth and invasion capabilities,which makes complete surgical resection almost impossible.Despite various treatment methods such as surgery,radiotherapy,and chemotherapy,glioma is still an incurable disease,and the median survival time of patients with GBM is shorter than 15 months.Thus,molecular mechanisms of GBM characteristic invasive growth need to be clarified to improve the poor prognosis.Glutamate ionotropic receptor kainate type subunit 1(GRIK1)is essential for brain function and is involved in many mental and neurological diseases.However,GRIK1’s pathogenic roles and mechanisms in GBM are still unknown.Single-nuclear RNA sequencing of primary and recurrent GBM samples revealed that GRIK1 expression was noticeably higher in the recurrent samples.Moreover,immunohistochemical staining of an array of GBM samples showed that high levels of GRIK1 correlated with poor prognosis of GBM,consistent with The Cancer Genome Atlas database.Knockdown of GRIK1 retarded GBM cells growth,migration,and invasion.Taken together,these findings show that GRIK1 is a unique and important component in the development of GBM and may be considered as a biomarker for the diagnosis and therapy in individuals with GBM.

Clinical application of reserved gastric tube in neuroendoscopic endonasal surgery for pituitary tumor

BACKGROUND The neuroendoscopic approach has the advantages of a clear operative field,convenient tumor removal,and less damage,and is the development direction of modern neurosurgery.At present,transnasal surgery for sphenoidal pituitary tumor is widely used.But it has been found in clinical practice that some patients with this type of surgery may experience post-operative nausea and vomiting and other discomforts.AIM To explore the effect of reserved gastric tube application in the neuroendoscopic endonasal resection of pituitary tumors.METHODS A total of 60 patients who underwent pituitary adenoma resection via the endoscopic endonasal approach were selected and randomly divided into the experimental and control groups,with 30 in each group.Experimental group:After anesthesia,a gastric tube was placed through the mouth under direct vision using a visual laryngoscope,and the fluid accumulated in the oropharynx was suctioned intermittently with low negative pressure throughout the whole process after nasal disinfection,during the operation,and when the patient recovered from anesthesia.Control group:Given the routine intraoperative care,no gastric tube was left.The number of cases of nausea/vomiting/aspiration within 24 h post-operation was counted and compared between the two groups;the scores of pharyngalgia after waking up,6 h post-operation,and 24 h postoperation.The frequency of postoperative cerebrospinal fluid leakage and intracranial infection were compared.The hospitalization days of the two groups were statistically compared.RESULTS The times of postoperative nausea and vomiting in the experimental group were lower than that in the control group,and the difference in the incidence of nausea was statistically significant(P<0.05).After the patient woke up,the scores of sore throat 6 h after the operation and 24 h after operation were lower than those in the control group,and the difference was statistically significant(P<0.05).The number of cases of postoperative cerebrospinal fluid leakage and intracranial infection was higher than that of the control group,but there was no statistically significant difference from the control group(P>0.05).The hospitalization days of the experimental group was lower than that of the control group,and the difference was statistically significant(P<0.05).CONCLUSION Reserving a gastric tube in the endoscopic endonasal resection of pituitary tumors,combined with intraoperative and postoperative gastrointestinal decompression,can effectively reduce the incidence of nausea,reduce the number of vomiting and aspiration in patients,and reduce the complications of sore throat The incidence rate shortened the hospitalization days of the patients.

Positioning and design by computed tomography imaging in neuroendoscopic surgery of patients with chronic subdural hematoma

BACKGROUND Neuroendoscopy is a very useful technique to Chronic Subdural Hematoma(CSH).But how to achieve the goal of treatment more minimally invasive?AIM To develop a simple,fast and accurate preoperative planning method in our way for endoscopic surgery of patients with CSH.METHODS From June 2018 to May 2020,forty-two patients with CSH,admitted to our hospital,were performed endoscopic minimally invasive surgery;computed tomography(CT)imaging was employed to locate the intracerebral hematoma and select the appropriate endoscopic approach before the endoscopic surgery.The clinical data and treatment efficacy were analyzed.RESULTS According to the learning of CT scanning images,the surgeon can accurately design the best minimally invasive neuroendoscopic surgical approach and realize the precise positioning and design of the drilling site of the skull and the size of the bone window,so as to provide the most effective operation space with the smallest bone window.In this group,the average operation time was only about 1 h,and the clearance rate of hematoma was about 95%.CONCLUSION Patients with CSH can achieve good therapeutic effect by using our way to positioning and design to assist the operation of CSH according to CT scan and image,and our way is very useful and necessary.

Advances in the mechanism of action of metformin in pituitary tumors

Pituitary tumors are common intracranial tumors,but when faced with drugresistant or aggressive tumors,existing medical measures may not provide good control,leading to progression and deterioration.Metformin,a traditional hypoglycemic drug,has recently been discovered to have multiple functions including antitumor effects.There have been studies on the mechanism of metformin for the treatment of pituitary tumors,but it is uncertain whether it will provide new adjuvant or alternative therapies for the treatment of these tumors.We analyzed the potential mechanisms of action of metformin with respect to the inhibition of pituitary tumor growth and hormone secretion by reviewing the available literature.

Neuroprotective effect of baicalin on focal cerebral ischemia in rats

Baicalin, a flavonoid compound from the root of the herb Scutellaria baicalensis Georgi, has been widely used to treat patients with inflammatory disease. The aim of this study was to assess the efficacy of baicalin in a rat model of focal cerebral ischemia. Adult male Sprague-Dawley rat models of cerebral artery occlusion were established and then randomly and equally divided into three groups： ischemia（cerebral ischemia and reperfusion）, valproic acid（cerebral ischemia and reperfusion ＋ three intraperitoneal injections of valproic acid; positive control）, and baicalin（cerebral ischemia and reperfusion ＋ intraperitoneal injection of baicalin for 21 days）. Neurological deficits were assessed using the postural reflex test and forelimb placing test at 3, 7, 14, and 21 days after ischemia. Rat cerebral infarct volume was measured using 2,3,5-triphenyltetrazolium chloride（TTC） staining method. Pathological change of ischemic brain tissue was assessed using hematoxylin-eosin staining. In the baicalin group, rat neurological function was obviously improved, cerebral infarct volume was obviously reduced, and the pathological impairment of ischemic brain tissue was obviously alleviated compared to the ischemia group. Cerebral infarct volume was similar in the valproic acid and baicalin groups. These findings suggest that baicalin has a neuroprotective effect on cerebral ischemia.

Efficacy evaluation of neuroendoscopy vs burr hole drainage in the treatment of chronic subdural hematoma:An observational study

BACKGROUND Chronic subdural hematoma(CSDH)is a common disease in neurosurgery.The traditional treatment methods include burr hole drainage,bone flap craniectomy and other surgical methods,and there are certain complications such as recurrence,pneumocephalus,infection and so on.With the promotion of neuroendoscopic technology,its treatment effect and advantages need to be further evaluated.AIM To study the clinical effect of endoscopic small-bone approach in CSDH.METHODS A total of 122 patients with CSDH admitted to our hospital from August 2018 to August 2021 were randomly divided into two groups using the digital table method:the neuroendoscopy group(n=61 cases)and the burr hole drainage group(n=61 cases).The clinical treatment effect of the two groups of patients with CSDH was compared.RESULTS At the early postoperative stage(1 d and 3 d),the proportion of 1/2 re-expansion of brain tissue in the hematoma cavity and the proportion of complete reexpansion was higher in the neuroendoscopy group than in the burr hole drainage group,and the difference between the two groups was statistically significant(P<0.05).The recurrence rate of hematoma in the neuroendoscopy group was lower than that in the burr hole drainage group,and the difference between the two groups was statistically significant(P<0.05).No intracranial hematoma,low cranial pressure,tension pneumocephalus or other complications occurred in the neuroendoscopy group.CONCLUSION The neuroendoscopic approach for the treatment of CSDH can clear the hematoma under direct vision and separate the mucosal lace-up.The surgical effect is apparent with few complications and definite curative effect,which is worthy of clinical promotion and application.

INTRAOPERATIVE LOCALIZATION OF CORTICAL MOTOR EVOKED POTENTIALS IN CENTRAL SULCUS LESIONS

Objective To study direct cortical electrical stimulation technique for the recording of motor evoked potentials under general anesthesia in central sulcus lesions. Methods The largest N20-P25 response was recorded from postcentral gyrus by intraoperative monitoring of cortical motor evoked potentials in 10 patients with intracranial lesions near or in the central area. The muscles of upper extremity in all patients were activated by delivering stimulus to cortical areas continuously. Moving the cortical electrodes forward, the largest P20-N25 response, SEP phase reversal,was obtained as a motor center stimulus. In this site of cortex, a short train stimulation elicited reproducible muscle action potentials that could be observed from the oscilloscope without averaging.Results MEPs can be recorded, pre-and post-operatively, without motor deficits of upper limbs in all patients.Conclusion This technique seems to be preferable for intraoperative localization of motor evoked potentials in central sulcus lesions under total intravenous anesthesia.

MECHANISM OF PATHOLOGICAL CHANGES OF INTRAVENTRICULAR HEMORRHAGE IN DOGS

Objective To probe the mechanism of pathological changes of intraventricular hemorrhage(IVH). Methods The evaluation of neurological status,serial CT scans and pathological examination were applied on the canine model of IVH. The ventricular volume and blood clot volume were measured based on the CT images. Results The normal adult canine ventricle tend to be slitlike. After injection, the ventricle was obviously dilated by the blood clot. The linear regression of ventricular volume against blood clot volume was significant in the first week. From then on, however, while the clots continued to shrink, the ventricular volume showed progressive enlargement. The clots were lysed completely within 3 to 4 weeks. The linear regression of the degree of ventricular dilatation against the first clot volume was also significant. In the pathological examination, we found the ependymal lining of ventricular system was destroyed and neurons in the subependymal areas developed acidophil necrosis, which was prominent around Sylvian aqueduct. Conclusion Hemorrhagic ventricular dilatation(HVD) is a prominent feature of IVH and also is a strong indicator for poor prognosis. Ischemic changes of periventricular neurons in some important structures may be the most direct cause for poor outcome of IVH. It may be induced by periventricular vascular structures compressed by HVD, increased intracranial pressure, cerebral vasospasm and others.

Dynamic expression of cerebral cortex and hippocampal glutamate transporters in a rat model of chest compression-induced global cerebral ischemia

The present study established a rat model of global cerebral ischemia induced by chest compression for six minutes to dynamically observe expressional changes of three glutamate transporters in the cerebral cortex and hippocampus. After 24 hours of ischemia, expression of glutamate transporter-1 significantly decreased in the cerebral cortex and hippocampus, which was accompanied by neuronal necrosis. At 7 days post-ischemia, expression of excitatory amino acid carrier 1 decreased in the hippocampal CA1 region and cortex, and was accompanied by apoptosis Expression of glutamate-aspartate transporter remained unchanged at 6 hours 7 days after ischemia. These results suggested that glutamate transporter levels were altered at different periods of cerebral ischemia.

Influence of moderate hypothermia on cerebral oxygenation in pigs with intracranial hypertension

BACKGROUND： Moderate hypothermia is one of the effective therapeutic methods for head injury in recent years, there are many mechanisms of moderate hypothermia for brain protection, and its influence on cerebral oxygenation is also one of them. OBJECTIVE： To observe the influence of moderate hypothermia on cerebral oxygenation of animals with acute intracranial hypertension, and further investigate the protective mechanism of moderate hypothermia. DESIGN： A randomized controlled trial. SETTING： Department of Neurosurgery, Renji Hospital affiliated to the Medical College of Shanghai Jiao Tong University. MATERIALS： Twenty healthy little pigs, either male or female, weighing 4.5-5.5 kg, were used. Neurotrend-typed multiparameter monitoring system （Diametrics Company, British）; CMA/100 micro-injection pump （Carnegie Company, Sweden）. METHODS： The experiment was conducted in the Changzheng Hospital affiliated to the Second Military Medical University of Chinese PLA in November, 2001. The pigs were randomized into two groups： the normothermia group （control group, n =10） and moderate hypothermia group （n =10）. ① Bilateral femoral arteries were separated, one was connected to pressometer for monitoring mean arterial pressure （MEP）, and the other for analysis of blood gases [including peripheral blood pH value, arterial partial pressure of carbon dioxide （PaCO2）, arterial partial pressure of carbon dioxide （PaCO2）, HCO3-]. ② Rectal temperature was monitored with mercurial thermometer. ③ Intracranial pressure was monitored using Camino optic ICP probe placed in the subdural space. ④ Neurotrend multiparameter monitoring sensor was inserted into the white matter for about 4 cm to determine cerebral perfusion pressure （CPP, CPP=MAP（ICP）, brain tissue partial oxygen pressure （PO2）, partial pressure of carbon dioxide （PCO2）, HCO3- and brain temperature. The rectal temperature of animals in the moderate hypothermia group was lowered to 34 ℃ using ice bags, and the body temperature was maintained at 33-35 ℃ for 2 hours. The changes of the parameters were observed continuously, and the pigs in the normothermia group were not treated with cooling. MAIN OUTCOME MEASURES： ① MAP, ICP, rectal temperature, CCP; Indexes of cerebral oxygenation detected with Neurotrend-typed multiparameter monitoring system; ② Results of blood gases analysis in the moderate hypothermia group. RESULTS： All the 20 pigs were involved in the analysis of results. ① MAP, ICP, rectal temperature, CCP and indexes of cerebral oxygenation： In the moderate hypothermia group, the ICP after cooling was obviously lower than that before cooling [（3.31±1.19）, （5.33±0.95） kPa, P 〈 0.05], CCP was higher, brain tissue PCO2 [（12.03±1.73）, （10.59±2.01） kPa, P 〈 0.05], and brain tissue pH value was higher [（7.03± 1.63）, （9.40±1.30） kPa, P 〈 0.05], whereas the brain temperature was decreased as compared with that before cooling [（34.9±0.3）, （37.2±0.2） ℃, P 〈 0.05]. ② Results of blood gases analysis in the moderate hypothermia group： There were no significant differences in the parameters of peripheral arterial blood gases analysis before and after cooling in the moderate hypothermia group （P 〉 0.05） CONCLUSION： Moderate hypothermia will not impair the cerebral oxygenation, and it can reduce brain tissue CO2 and decrease brain tissue acidosis.

Management and operation of extra-large Fangcang hospitals:experience and lessons from containing the highly contagious SARS-CoV-2 Omicron in Shanghai,China

Introduction Omicron is more contagious and stealthier than the previous strains.The basic reproduction number of Omicron is around 8–12,whereas that of the previous mainstream strain Delta is only 5–8[1].Omicron’s symptoms are relatively mild[2]compared with Delta’s symptoms;however,Omicron’s transmission ability is very strong,and its risk to children and the elderly remains high[3].In addition,the vaccine’s preventive effect on Omicron has weakened.Therefore,Omicron can easily cause a rapid outbreak in a city.The population density of megacities and the limited public health resources further exacerbate the difficulty of Omicron prevention and control.

Exosomes derived from bone marrow mesenchymal stem cells inhibit neuroinflammation after traumatic brain injury

Exosomes derived from bone marrow mesenchymal stem cells can inhibit neuroinflammation through regulating microglial phenotypes and promoting nerve injury repair.However,the underlying molecular mechanism remains unclear.In this study,we investigated the mechanism by which exosomes derived from bone marrow mesenchymal stem cells inhibit neuroinflammation.Our in vitro co-culture experiments showed that bone marrow mesenchymal stem cells and their exosomes promoted the polarization of activated BV2 microglia to their anti-inflammatory phenotype,inhibited the expression of proinflammatory cytokines,and increased the expression of anti-inflammatory cytokines.Our in vivo experiments showed that tail vein injection of exosomes reduced cell apoptosis in cortical tissue of mouse models of traumatic brain injury,inhibited neuroinflammation,and promoted the transformation of microglia to the anti-inflammatory phenotype.We screened some microRNAs related to neuroinflammation using microRNA sequencing and found that microRNA-181b seemed to be actively involved in the process.Finally,we regulated the expression of miR181b in the brain tissue of mouse models of traumatic brain injury using lentiviral transfection.We found that miR181b overexpression effectively reduced apoptosis and neuroinflamatory response after traumatic brain injury and promoted the transformation of microglia to the anti-inflammatory phenotype.The interleukin 10/STAT3 pathway was activated during this process.These findings suggest that the inhibitory effects of exosomes derived from bone marrow mesenchymal stem cells on neuroinflamation after traumatic brain injury may be realized by the action of miR181b on the interleukin 10/STAT3 pathway.

microRNA-455-5p alleviates neuroinflammation in cerebral ischemia/reperfusion injury

Neuroinflammation is a major pathophysiological factor that results in the development of brain injury after cerebral ischemia/reperfusion.Downregulation of microRNA(miR)-455-5p after ischemic stroke has been considered a potential biomarker and therapeutic target for neuronal injury after ischemia.However,the role of miR-455-5p in the post-ischemia/reperfusion inflammatory response and the underlying mechanism have not been evaluated.In this study,mouse models of cerebral ischemia/reperfusion injury were established by transient occlusion of the middle cerebral artery for 1 hour followed by reperfusion.Agomir-455-5p,antagomir-455-5p,and their negative controls were injected intracerebroventricularly 2 hours before or 0 and 1 hour after middle cerebral artery occlusion(MCAO).The results showed that cerebral ischemia/reperfusion decreased miR-455-5p expression in the brain tissue and the peripheral blood.Agomir-455-5p pretreatment increased miR-455-5p expression in the brain tissue,reduced the cerebral infarct volume,and improved neurological function.Furthermore,primary cultured microglia were exposed to oxygen-glucose deprivation for 3 hours followed by 21 hours of reoxygenation to mimic cerebral ischemia/reperfusion.miR-455-5p reduced C-C chemokine receptor type 5 mRNA and protein levels,inhibited microglia activation,and reduced the production of the inflammatory factors tumor necrosis factor-αand interleukin-1β.These results suggest that miR-455-5p is a potential biomarker and therapeutic target for the treatment of cerebral ischemia/reperfusion injury and that it alleviates cerebral ischemia/reperfusion injury by inhibiting C-C chemokine receptor type 5 expression and reducing the neuroinflammatory response.

PARAPETROSAL PRESIGMOID APPROACH FOR PETROCLIVAL TUMORS

Objective To discuss the operative technique of parapetrosal presigmoid approach for patients with petroclival tumors and its outcome. Methods 16 petroclival tumors have been microsurgical treated with parapetrosal presigmoid approach and the clinical data were analysed retrospectively. Results In all patients, 9 had meningiomas, 3 epidermoid cysts, 2 pontine gliomas, and 2 schwannomas. Total resection was performed in 12 patients, subtotal resection in 3, and near subtotal resection in 1. Temporary post-operative cranial nerve paresis occurred in 3 patients but no CSF leakage and mortality ever occurred. Conclusion This approach is simpler and safer than other more extensive transpetrosal approaches. It can expose sufficiently the petroclival regions and facilitate tumor removal and provides good clinical outcome.

中国新诊断胶质母细胞瘤患者实际治疗方案与Stupp方案的一致性比较

目的评估中国新诊断胶质母细胞瘤(glioblastoma multiforme,GBM)患者实际接受的治疗方案与指南推荐的Stupp方案的一致性。方法纳入202例新诊断GBM患者,评估实际接受的治疗方案与Stupp方案一致的患者比例,以及不符合Stupp方案的原因。结果研究发现,仅15.8%的GBM患者接受了与Stupp方案一致的治疗。治疗方案的不一致主要是由于同步放化疗阶段替莫唑胺剂量>75 mg/m^(2)(58/120;48.3%)和治疗持续时间<42 d(84/120;70.0%),以及辅助治疗阶段替莫唑胺剂量<150 mg/m^(2)(89/101;88.1%)。接受符合Stupp方案治疗的患者的中位总生存期(27.09 vs 18.21个月)和无进展生存期(14.27 vs 12.10个月)更长。结论需要提高中国GBM患者实际接受的治疗方案与Stupp方案的一致性。

Pipeline Embolization Device for intracranial aneurysms presenting with mass effect:a large Chinese cohort

Background Unruptured intracranial aneurysm treatment aims to reduce the risk of aneurysm rupture and bleeding,relieves symptoms and improve the quality of life for patients.This study aimed to assess the safety and efficacy of Pipeline Embolization Device(PED,Covidien/Medtronic,Irvine,CA)treatment for intracranial aneurysms presenting with mass effect in real-world settings.Methods We selected patients from the PED in China Post-Market Multi-Center Registry Study with mass effect presentation.The study endpoints included postoperative mass effect deterioration and mass effect relief at follow-up(3–36 months).We conducted multivariate analysis to identify factors associated with mass effect relief.Subgroup analyses by aneurysm location,size and form were also performed.Results This study included 218 patients with a mean age of 54.3±11.8 years and a female predominance of 74.0%(162/218).The postoperative mass effect deterioration rate was 9.6%(21/218).During a median follow-up period of 8.4 months,the mass effect relief rate was 71.6%(156/218).Notably,immediate aneurysm occlusion following treatment was significantly associated with mass effect relief(OR 0.392,95%CI,0.170 to 0.907,p=0.029).Subgroup analysis demonstrated that adjunctive coiling contributed to mass effect relief in cavernous aneurysms,while dense embolism impeded symptom relief in aneurysms<10mm and saccular aneurysms.Conclusions Our data confirmed the efficacy of PED in relieving mass effect.The findings of this study provide support for endovascular treatment to alleviate mass effect in unruptured intracranial aneurysms.Trial registration number NCT03831672.

Hypertensive intracranial hematomas: endoscopic-assisted keyhole evacuation and application of patent viewing dissector

To study the effect of endoscopic assisted keyhole operation (EAKO) on treating hypertensive intracranial hematomas and the value of our patent dissector appli ed during the operation Methods A total of 25 patients with hypertensive intracranial hematomas underwent endos copic assisted keyhole evacuation, during which, the viewing dissector, which h ad recently achieved national patent, was connected to the tip of endoscope and used to help dissect hematomas The outcome of this procedure were compared wit h those of 22 comparable cases undergone conventional surgical treatment (large or smaller craniotomy) The items for comparison included the volum e of remaining hematoma, the duration of operation, postsurgical Glasgow Coma Sc ale (GCS) and Glasgow Outcome Scale (GOS) Results Remaining hematoma was ascertained 48 h after operation with the use of comp uterized tomography (CT) scans In the case of EAKO, nearly complete evacuation (>84%) was achieved in 21 cases; GCS was evaluated at 7 d postsurgery result ing in GCS >12 in 9 patients, GCS 9-12 in 12 patients and GCS <9 in 4 patients The follow up period ranged from 6 to 21 mon GOS was estimated at half a year and good recovery rate as defined by GOS was assigned to 76% of the EAKO pa tients There are significant differences in the volumes of remaining hematomas and the duration of operation between the EAKO and craniotomy group ( P <0 0 5) In addition, better clinical outcomes were obtained in EAKO Conclusion EAKO has the advantage of being minimally invasive, improving surgical results a nd the prognosis of hypertensive intracranial hematoma patients We conclude th at keyhole operation is a safe, effective alternative for removal of hypertensiv e intracranial hematoma, particularly during acute stages

Effect of arousal methods for 175 cases of prolonged coma after severe traumatic brain injury and its related factors

Objective: To determine the effect of arousal methods for prolonged coma of 175 patients with severe traumatic brain injury and related factors.Methods: 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. Results: 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. Conclusions: Application of appropriate arousal procedures improves recovery of consciousness in patients with prolonged coma.

Recent advance and current status of management of head trauma in China

It is estimated that more than 1 million Chinese people sustain traumatic brain injury （TBI） annually, nearly 10% of whom are dead and 30% are compli-cated with physical, cognitive, behavioral and/or psychosocial impairments in China. A lot of experimental researches and clinical trials of head trauma have been made in China recently, which improves the understanding of pathological mechanisms and prognosis of severe traumatic brain injury.

Alteration of microRNA expression in cerebrospinal fluid of unconscious patients after traumatic brain injury and a bioinformatic analysis of related single nucleotide polymorphisms

Purpose： 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）. Methods： 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. Results： 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. C.ondusion： 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.