The Basal And Clinical Researches On The Relationship Between The Cerebrospinal Fluid Protein S100B Concentrations And The Prognosis Of Comatose Patients

Background&Objectives:Consciousness consists of two parts--the waked state and the components of consciousness. The former means the waking state with normal sleepy cyclicity.The later involves thinking,affection,memory,perception,behavior and so on.The clear consciousness state of human beings mostly depends on the normal functions and the interaction of the cerebral cortex and the ascending reticular activating system(ARAS).ARAS is related to the waking state,which is located in the cerebral central axis,While the cerebral cortex is related to conscious components.So the most important anatomic structure which affects the consciousness is reticular formation(RF).Any disease which damages the ARAS will cause consciousness disorders.Coma is a state of serious consciousness disorder which is caused by many diseases, and also represents the dysfunction of the brain. The lasting time for coma is usually less than one month,and the light comatose patients will come around soon,while the deep ones may die.The results of comatose patients include death,vegetative state(VS),some extent functional incapacitation,and complete neuro-functional rehabilitation.It is conveived that many people prefer dying to living in VS or largely depending on others.If there is an effective prognosis program, the families of the comatose patients can accept a relativly rational therapy program for them.Recently,the mechanism of coma is much clearer,which results from the development of neuro-anatomy and molecular biology.The development of neuro-intensive care technique makes many comatose patients get promptly effective therapy,but at the same time,there are more VS patients post coma and with disabilities, which bring heavy burdens for the families and the society. Therefore,the research in prognosis factors that affect the comatose patients is reconstructed.We hope to find an effective research way to forecast the therapy results of the coamtose patients effectively and guide how to make a relative clinical treatment schedule.It is shown that many factors can affect the prognosis of the comatose patients,such as etiological factors,ages,the therapeutic methods and so on. All of these markers are mostly focused on the clinical factors.However,many biological markers can also affect the prognosis of the comatose patients,for instance, neurotransmitters, acceptors,the concentrations of blood glucose and so on.In the recent years,many researchers study on neuro-special secretory proteins,especially of S100B protein and neuron specific enolase. S100B protein is the dominating and most active member of S100 family in brain,about 96% located in cerebral.So,S100B protein is known as the neuro-specific protein which is mostly synthesised in astrocyte,and also in other gliocyte,neuron in different encephalic regions,synaptic knob and synaptolemma.It is usually located in hyalomitome,and transported to the outside of cells by autocrine and paracrine secretion.S100B protein has comprehensive biologic functions, neurotrophy when under physiological concentration(ng/l),can promote the growth and restoration of neurons.While it can also porduce cytotoxicity when in high concentration(ug/l),leading to depress the growth of cellizes,inducing cell apoptosis,even necrosis of the neurons.When the brain is damaged, neuroglial cell and neurons are also destroyed,so the S100B protein is percolated to the outside of cells.Since it is deemed that S100B protein is the most specific protein so far it can show the degree of brain injury.In our study,firstly,we analyse the clinical characters of coma.Secondly,we compare the S100B protein concentrations in cerebrospinal fluid(CSF) when patients are in coma and palinesthesia,and also we calculate the correlation of the initial GCS and the S100B protein concentrations in CSF when the patients are in coma.Based on those results,we approach to the relationship between the S100B protein concentrations in CSF and the prognosis of the comatose patients.Materials&Methods:1. There are 57 comatose patients with complete information in HuaDu People's Hospital between March and December in 2009.There are 39 male patents and 18 female patients,aging from 10 to 85.There are 32 traumatic comatose patients,19 comatose patients caused by cerebral hemorrhage,4 by cerebral ischemic stroke and 2 other patients caused by cerebral ischemic and hypoxia.2. The standards of choosing patients are as follows,①the patients reached hospital in 6 hours when disease begins.②Without any disorders of other systems.③The initial Glasgow coma score(GCS) is less than 8。④Excluding the patients without name,family and workplace.3. All of the patients accept active life surpporting treatment and etiological treatment when arriving in hospital,and are also being monitored the vital sign.Besides the surgical intervention methods,all of the patients are given medicing,such as naloxone, ganglioside and xingnaojing,then accept hyperbaric oxygenation and acupuncture treatments in early stage.Evaluating the GCS dynamically.If the patient is still in coma a month later,then add some medicine such as madopar and bromocriptine.In our study,we follow the trace of 57 patients for 6 months.The standard of waking is that the patient can follow simple instructive orders.4. All of the patients families firstly sign informed consents,and then we will get the first 5ml CSF sample by lumbar puncture between 24 hours and 48 hours when they arrived in hospital.Swing the sample for 15 minutes and then centrifugate for 20 minutes by 3000 r/min. Supernatant fluid is collected in two tubes and then located in -20℃until the secondary sample is collected.5. Evaluating the patients dynamically,when they come back to consciousness,we will get the secondary 5ml CSF sample by lunbar puncture immediately. Swing the sample for 15 minutes and then centrifugate for 20 minutes by 3000 r/min. Supernatant fluid is collected in two tubes and then located in -20℃until the secondary samples are completely collected.6. We detect the S100B protein concentrations in the first and second samples respectively by double-antibody sandwich enzyme-linked immunosorbent assay (ds-ELISA).7. Statistics analysis:we take SPSS 13.0 to deal with the dates.The comparison of the CSF S100B protein concentrations is calculated by Paired-Samples T test. The relationships between the initial GCS and the GOS of 6 months are evaluated with the methods of Spearman Related analysis of Bivariate about the 17 palinesthesia patients. The correlation of the initial GCS and the S100B protein concentrations in CSF of the 17 coamtose patients is calculated by Pearson Related analysis of Bivariate. It is significant when P<0.05.Results:1. hofactors are as follows,traumatic brain injury(TBI)(56.1%), Cerebral Hemorrhage(33.3%), cerebral ischemic stroke(7.0%), cerebral ischemic and hypoxia(3.5%) and so on.2. The investigation of the clinical treatment:All of the 57 patients,12 died,which means that the fatality rate is 21.1%.There are 25 families who give up the treatments because of their economic situations and other reasons,about 43.9%,which involves 18 patients died out of hospital,5 patients are living in VS,and 2 patients are with severe disability.While 3 patients are living in PVS.The last 17 patients have come around,and the waking rate is about 29.8%.3. The relationship between the S100B protein concentrations in CSF and comaBy detecting,the S100B protein concentration in CSF is remarkably lower when the patients come around (t=3.735, P=0.002). There is markedly negative correlation of the initial GCS and the S100B concentrations in CSF of the 17 comatose patients(P=0.002,r=-0.689).There is a remarkably positive relationship between the initial GCS and the GOS of 6 months(r=0.416,P=0.001).Conclusions:1. The etiological factors are multiplex but coma caused by anydisease is a severe clinical symptom.If the patient can not accept treatment in time,then he will have a bad recovery and the mortality or the disability rate will become higher.And also,both the supporting from families and the economical conditions are important factors which have influences on the therapy of comatose patients.We firstly should make the comatose patients' vital signs stable while give them effective etiological treatments.Then we should stop the situations from exacerating, prophylaxis and deal with the complications in time.2. The S100B protein concentrations in CSF can be an effective chemical marker for forecasting the chances of palinesthesia about the comatose patients.3. The concentrations of S100B protein in CSF can sensitivitily show the degree of brain damage.However,both of the concentrations of S100B protein in CSF and the initial GCS can be used to forecast the chances of palinesthesia about the comatose patients more effectively.However,if the comatose patients with a lower initial GCS can accept active etiological therapies and rehabilitation in time,the survival rate of the comatose patients may be higher and they could have better therapy results.