Neurological diseases are a major health concern, and brain injury is a typical pathological process in various neurological disorders. Different biomarkers in the blood or the cerebrospinal fluid are associated with specific physiological and pathological processes. They are vital in identifying, diagnosing, and treating brain injuries. In this review, we described biomarkers for neuronal cell body injury (neuron-specific enolase, ubiquitin C-terminal hydrolase-L1, αII-spectrin), axonal injury (neurofilament proteins, tau), astrocyte injury (S100β, glial fibrillary acidic protein), demyelination (myelin basic protein), autoantibodies, and other emerging biomarkers (extracellular vesicles, microRNAs). We aimed to summarize the applications of these biomarkers and their related interests and limits in the diagnosis and prognosis for neurological diseases, including traumatic brain injury, status epilepticus, stroke, Alzheimer's disease, and infection. In addition, a reasonable outlook for brain injury biomarkers as ideal detection tools for neurological diseases is presented.
Humans ; Biomarkers/cerebrospinal fluid* ; Nervous System Diseases/diagnosis* ; Brain Injuries/metabolism* ; Phosphopyruvate Hydratase/cerebrospinal fluid* ; Glial Fibrillary Acidic Protein/blood* ; S100 Calcium Binding Protein beta Subunit/blood* ; tau Proteins/cerebrospinal fluid* ; Ubiquitin Thiolesterase/blood* ; Myelin Basic Protein/cerebrospinal fluid* ; Neurofilament Proteins/blood* ; MicroRNAs/blood* ; Brain Injuries, Traumatic/metabolism*

To investigate the association between chronic unpredictable mild stress (CUMS)-induced depressive-like behavior in rats and expressions of brain-derived neurotrophic factor (BDNF) and S100β in the hippocampal and prefrontal cortex. Rats were randomly assigned to three groups:saline control group,saline+CUMS group,and citalopram +CUMS group. CUMS was used for depression modeling in rats. Depressive-like behavior in rats were evaluated by open-field test,sucrose preference test,and novel object recognition test. S100β and BDNF expressions were tested by enzyme-linked immunosorbent assay. Rats in the saline+CUMS group had significantly lower score in sucrose preference [(52.48±13.14)%],basic motor tasks [(845.8±371.4)s],fine motor tasks [(565.6±211.9)s],and longer resting time [(282.6±11.8)s] compared to the control group [(84.30±6.15)% (=7.49,=0.000),(1239.1±281.6)s (=2.83,=0.008),(801.8±150.9)s (=3.05,=0.003),(268.2±12.8)s (=2.72,=0.001)]. Compared with the citalopram+CUMS group,rats from the saline+CUMS group also showed significantly lower results in sucrose preference [(80.55±11.31)%,=5.39,=0.000],basic motor tasks [(1156.4±314.7)s,=2.13,=0.031],and fine motor tasks [(736.1±150.0)s,=2.21,=0.008]. There were no significant differences in the expression of hippocampal and prefrontal BDNF between these two groups,but rats from the saline+CUMS group expressed significantly higher levels of S100β compared to rats from the citalopram+CUMS group [(13.22±2.23) ng/g (10.55±2.72) ng/g,=2.67,=0.014]. Pearson correlation analysis revealed that the expression of S100β was positively correlated with the expression of BDNF in the prefrontal cortex and hippocampus (=0.35,=0.034;=0.36,=0.034).The novel object recognition index was positively correlated with the expression of BDNF in the hippocampus(=0.38,=0.021),and the duration of fine-motor activities was negatively correlated with S100β in the prefrontal cortex (=-0.36,=0.037). Different types of depressive behaviors in rats induced by CUMS are associated with the selective expression of S100β and BDNF in two different brain cortex. S100β protein and BDNF may independently participate in the pathogenesis of depression.
Animals ; Antidepressive Agents ; Brain-Derived Neurotrophic Factor ; metabolism ; Citalopram ; Depression ; metabolism ; Disease Models, Animal ; Frontal Lobe ; metabolism ; Hippocampus ; metabolism ; Random Allocation ; Rats ; S100 Calcium Binding Protein beta Subunit ; metabolism ; Stress, Psychological

OBJECTIVE: To research the serum levels of BDNF, H2S and S-100β as metabolic product of hippocampus and cerebral cortex in moderate to severe obstructive sleep apnea hypopnea syndrome(OSAHS) patients before and after surgery, and to analyze their correlations with cognitive impairment. METHOD: Forty-four randomly selected diagnosed OSAHS patients were divided into two groups according to Montreal Cognitive Assessment (MoCA), 19 cases in cognitively normal group and 25 cases in cognitive dysfunction group. Cases in cognitive dysfunction group underwent UPPP oriented surgery, and received 6 months follow-up, 21 cases were remained as treament group, 4 cases lost. 19 cases of healthy subjects were randomly selected as the normal control group. All groups were detected for the serum BDNF, H2S and S-100β levels to analyze the correlations between the biochemical indexes and sleep disorders indexes, hypoxia levels and cognitive function scores. RESULT: (1) In the comparison between the treatment group and the normal control group regarding PSG monitoring results, the AHI, I + II, LA/HT and SLT90% indexes of OSAHS patients increased, and the III + IV phase, REM phase, MSaO2 and LSaO2 decreased. In the comparison between the cognitive dysfunction group and the cognitively normal group, the III + IV, REM and LSaO2 indexes of the cognitive dysfunction group decreased. (2) In the comparison between cognitive dysfunction group and cognitively normal group, and between the treatment group and the normal control group, BDNF and H2S levels increased and S-100β levels decreased, and the MoCA total scores, attention, memory/delayed recall scores decreased. (3) The correlation between biochemical indexes with PSG indexes was as follows. The serum BNDF and H2S levels were negatively correlated with AHI index. The serum BNDF and H2S levels were positively correlated with III + IV stage, REM stage and MSaO2 indexes. The S-100β level was positively correlated with AHI index, and S-100β levels were negatively correlated with III + IV stage, REM stage, MSaO2 and LSaO2 indexes. (4) The correlation between biochemical indexes and MoCA scores was as follows. The serum BNDF and H2S levels were positively correlated with MoCA total scores, attention, and memory/delayed recall scores. The serum S-100β levels were negatively correlated with MoCA total scores, attention and memory/ delayed recall scores. (5) The linear regression equation between MoCA total scores in cognitive dysfunction group of OSAHS patients and the serum BNDF, H2S and S-100β levels was as follows: Y(MoCA) = 40.131 + 0.22 X(BDNF) + 0.012 X(H2S)-0.647X(S-100β) (R2 = 0.461). CONCLUSION OSAHS patients with sleep disorder and nocturnal hypoxemia might suffer from cognitive dysfunction in which attention and memory predominates. Serum BNDF, H2S and S-100β levels, which could indirectly reflect the metabolic abnormalities degree of hippocampus and cerebral cortex, are sensitive indicators of early cognitive dysfunction in OSAHS patients.
Brain-Derived Neurotrophic Factor ; metabolism ; Cerebral Cortex ; physiopathology ; Cognition Disorders ; complications ; Hippocampus ; physiopathology ; Humans ; Hypoxia ; Memory ; Metabolic Diseases ; physiopathology ; S100 Calcium Binding Protein beta Subunit ; metabolism ; Sleep Apnea, Obstructive ; complications

OBJECTIVE: To study the expression of S100B and glial tibrillory acidic protein (GFAP) atter primary brainstem injury in rat and discuss the changes with brainstern injury time and their mechanism in the injury. METHODS: The brainstem injury animal model was established using the mechanical impacting method. The HE staining, Gless argentaffin staining and SP immunohistochemical method were applied to observe the changes of S100B and GFAP at different injury time. The immunostaining results were measured statistically with imaging analysis technology. RESULTS: A large number of S100B positive cells could be seen in 30 min. Afterward, expression increased gradually with time and peaked up in 24 h, and reversed back the normal in 72h. The GFAP positive cells showed rise continually in 30 min, and reached the peak in 48 h, then started to decrease, but still higher than that in control. CONCLUSION The expression of S100B and GFAP is correlated with post traumatic intervals after brainstem injury in rat, and may be useful in estimation post traumatic intervals and nerve regeneration.
Animals ; Brain Injuries/metabolism* ; Brain Stem/metabolism* ; Disease Models, Animal ; Glial Fibrillary Acidic Protein/metabolism* ; Immunohistochemistry ; Nerve Growth Factors ; Neuroglia ; Rats ; S100 Calcium Binding Protein beta Subunit/metabolism* ; S100 Proteins

OBJECTIVETo investigate the protective effect and mechanism of Xingnaojing(Traditional Chinese Medicine) injection on brain injury in rats.

METHODSSixty-three healthy adult male SD rats were randomly divided into 3 groups (n = 21): sham operation group, model group, xingnaojing group. The model of traumatic brain injury model group and Xingnaojing group used the free fall impact injury method, the sham operation group underwent craniotomy, did not cause brain damage. Xingnaojing group in rats after 10 min by tail vein injection Xingnaojing injection 10 ml/(kg x d), model group and sham operation group were intravenously injected with 0.9% sodium chloride solution, three groups were administered continuously for 7 days. At administration of the seventh days compared the S-100B protein in the serum and neuro specific enolase (NSE) level, the water content of brain tissue, serum superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) content, and neurological function of rats among groups.

RESULTSCompared with the sham operation group, the nerve defect, brain water content, MDA, S100B protein and NSE levels were obvigusly increased in Xingnaojing group and model group; SOD, GSH-Px content decreased significantly; In Xingnaojing group nerve impairment and brain moisture were significantly lower than those of model group, the serum MDA, S-100B protein and NSE levels were significantly lower than those in the model group, the SOD, GSH-Px activity was significantly higher than that in the model group.

CONCLUSIONXingnaojing injection has protective effects on rat brain injury, and its mechanism may be related to reduce brain edema after traumatic brain injury and inhibit the reaction of oxygen free radical, protect nerve cells.

Animals ; Brain Injuries ; metabolism ; prevention & control ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Glutathione Peroxidase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Phosphopyruvate Hydratase ; metabolism ; Rats ; Rats, Sprague-Dawley ; S100 Calcium Binding Protein beta Subunit ; blood ; S100 Proteins ; metabolism ; Superoxide Dismutase ; metabolism

OBJECTIVE: To observe the changes of blood pressure and S-100B, neuron specific enolase (NSE) protein in hypertensive dogs with high fat diet after catheter-based renal sympathetic denervation. METHODS: Twelve Beagles were divided into an interventional group (n=6) and a sham-operation group (n=6). After baseline measurements, the Beagles were fed with lard oil for 3 months. After 3 months, the interventional group had renal sympathetic denervation by percutaneous catheter based radiofrequency ablation and the control group had renal angiography. The blood pressure, plasma S-100B, and NSE before the operation and 3 days, 1 week, 2 weeks, 1 month, 2 months and 3 months after the operation were measured. RESULTS: The dogs had significantly higher levels of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MBP) compared to its baselines (P<0.05). The SBP, DBP and MBP in the interventional group were significantly lower than those in the control group 1 month and 3 months after the operation (P<0.05). Three months after the operation, renal angiography in all dogs revealed no sign of renal artery stenosis. Plasma S-100B and NSE expression in the interventional group were higher than those in the control group 3 days, 1 week and 2 weeks after the operation (P<0.05). CONCLUSION Renal sympathetic denervation can significantly reduce the SBP, DBP and MBP in hypertensive dogs. The plasma S-100B and NSE may be used as indicators for assessment of renal nerve injury after renal sympathetic denervation.
Animals ; Blood Pressure ; Catheter Ablation ; Dogs ; Hypertension ; metabolism ; Kidney ; innervation ; surgery ; Phosphopyruvate Hydratase ; metabolism ; S100 Calcium Binding Protein beta Subunit ; metabolism ; Sympathectomy

OBJECTIVETo observe the protective effect of Shenfu Injection (SFI) pretreatment on brain of patients receiving aortic valve replacement (AVR) undergoing cardiopulmonary bypass (CPB).

METHODSThirty AVR patients undergoing CPB were randomly assigned to 2 groups, the control group and the experimental group, 15 cases in each group. SFI at 1.5 mL/kg (dissolved in 250 mL 5% glucose solution) was intravenously dripped to those in the experimental group 5 days before operation, once daily for 5 successive days. SFI at 1.5 mL/kg (dissolved in 250 mL 5% glucose solution) was intravenously dripped to those 30 min before anesthesia induction. Equal dose of normal saline was intravenously dripped to those in the control group, and the other procedures were the same as those for patients in the experimental group. The venous blood sample (2 mL) was drawn from the right internal carotid vein immediately after induction of anesthesia (T1),10 min after CPB (T2), 30 min after GPB (T3), 2 h after CPB (T4), 24 h after CPB (T5), and 48 h after CPB (T6), thus detecting the plasma levels of S100beta and neuron specific enolase (NSE). And patients' cognitive function was assessed with mini-mental state examination (MMSE) scale on the day before operation, the 2nd and the 7th day after operation.

RESULTSThere was no statistical difference in the levels of S1001 and NSE between the two groups at T1 (P > 0.05). There was statistical difference in the levels of S100beta and NSE between the two groups at T2, T3, T4, T5, T6, when compared with those at T1 (P <0.05). Besides, the levels of S100beta and NSE at T2, T3, T4, T5, T6 were lower in the experimental group than in the control group, showing statistical difference (P <0.05). The MMSE scores decreased on the 2nd day after operation in the two groups, showing statistical difference when compared with those on the day before operation (P <0.05). It was lowered more obviously in the control group. There was no statistical difference in the MMSE score between the 7th day post-operation and the day before operation (P >0.05).

CONCLUSIONSFI pretreatment had protective effect on brain in AVR patients undergoing CPB.

Brain ; drug effects ; metabolism ; Cardiopulmonary Bypass ; Cognition ; drug effects ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Heart Valve Prosthesis Implantation ; methods ; Humans ; Intraoperative Period ; Ischemic Preconditioning ; methods ; Male ; Middle Aged ; Phosphopyruvate Hydratase ; metabolism ; S100 Calcium Binding Protein beta Subunit ; metabolism

Carotid endarterectomy(CEA)has been proved to be an effective surgery to treat the cerebral ischemia caused by carotid atherosclerotic stenosis. However,there is still no effective mean for the early diagnosis of the CEA-related severe complications such as stroke and death. Many studies have explored the potential biomarkers for stroke alert,although there is still a long way to go for their actual application in clinical settings. The carotid atherosclerotic stenosis,the perioperative complications of CEA,and the stroke share similar pathogenic mechanisms,and some biomarkers such as S100B,matrix metalloproteinase 9,asymmetric dimethylarginine,and neuron-specific enolase have been studied in the clinical trails of CEA. This article summarizes recent advances in this field.
Biomarkers ; metabolism ; Endarterectomy, Carotid ; Humans ; Intraoperative Period ; Postoperative Complications ; prevention & control ; Risk Assessment ; S100 Calcium Binding Protein beta Subunit ; metabolism

OBJECTIVETo study the significance of cytokine IL-1α and S100&beta; expression in formation and evolution of different types of plaques in Alzheimer's disease.

METHODSThirty-four autopsy cases of Alzheimer's disease encountered during the period from 1982 to 2008 were retrieved from the archival files of Department of Pathology, Beijing Hospital. Tissue blocks were taken from hippocampus for dual immunostaining for IL-1α/A&beta; and S100&beta;/A&beta;.

RESULTSImmunohistochemical studied for IL-1α/A&beta; and S100&beta;/A&beta; delineated four different types of senile plaques: diffuse non-neuritic plaques, diffuse neuritic plaques, dense-core neuritic plaques and dense-core non-neuritic plaques. The numbers of IL-1α-positive microglias and S100&beta;-positive astrocytes associated with diffuse neuritic plaques were (7.29 ± 3.04) per mm(2) and (6.49 ± 2.20) per mm(2), respectively. In contrast, the numbers of IL-1α-positive microglias and S100&beta;-positive astrocytes associated with diffuse non-neuritic plaques, dense-core neuritic plaques and dense-core non-neuritic plaques were (3.24 ± 1.53) per mm(2) and (4.14 ± 1.77) per mm(2), (2.09 ± 1.37) per mm(2) and (2.25 ± 0.83) per mm(2), and (1.38 ± 0.90) per mm(2) and (0.58 ± 0.36) per mm(2), respectively. The numbers of IL-1α-positive microglias and S100&beta;-positive astrocytes associated with diffuse neuritic plaques were significantly higher than those of the other three types of plaques (P < 0.05).

CONCLUSIONThe IL-1α-positive microglias and S100&beta;-positive astrocytes may be of certain significance in transformation of diffuse non-neuritic plaques to diffuse neuritic plaques in Alzheimer's disease.

Aged ; Aged, 80 and over ; Alzheimer Disease ; metabolism ; pathology ; Astrocytes ; metabolism ; Female ; Hippocampus ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Interleukin-1alpha ; metabolism ; Male ; Microglia ; metabolism ; Middle Aged ; Nerve Growth Factors ; metabolism ; Plaque, Amyloid ; classification ; metabolism ; pathology ; S100 Calcium Binding Protein beta Subunit ; S100 Proteins ; metabolism

OBJECTIVETo determine the expression of S100-beta protein and glial fibrillary acidic protein (GFAP) in hippocampal astrocytes of rats with Alzheimer disease (AD) model rats, and observe the effect of butylphthalide on their expression.

METHODSSixty male adult rats were randomized equally into model group, butylphthalide group, and control group, and in the former two groups, AD models were established by injecting beta-amyloid protein 1-40 into the hippocampus. Sixty days later, the rats were sacrificed and the bilateral hippocampuses were taken for immunohistochemistry.

RESULTSThe number of cells positive for S100 and GFAP in the hippocampus in butylphthalide group were significantly higher than that in the control group (P/0.01), but lower than that in the model group (P/0.05).

CONCLUSIONThe expression of S100 protein and glial fibrillary acidic protein increased significantly in the hippocampal astrocytes of rats with AD, and butylphthalide can inhibit the increase of their expression.

Alzheimer Disease ; chemically induced ; metabolism ; Amyloid beta-Peptides ; Animals ; Benzofurans ; pharmacology ; Disease Models, Animal ; Glial Fibrillary Acidic Protein ; metabolism ; Hippocampus ; metabolism ; Male ; Nerve Growth Factors ; metabolism ; Neuroprotective Agents ; pharmacology ; Peptide Fragments ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; S100 Calcium Binding Protein beta Subunit ; S100 Proteins ; metabolism