Major advances have been made over the past few decades in identifying and managing disorders of consciousness (DOC) in patients with acquired brain injury (ABI), bringing the transformation from a conceptualized definition to a complex clinical scenario worthy of scientific exploration. Given the continuously-evolving framework of precision medicine that integrates valuable behavioral assessment tools, sophisticated neuroimaging, and electrophysiological techniques, a considerably higher diagnostic accuracy rate of DOC may now be reached. During the treatment of patients with DOC, a variety of intervention methods are available, including amantadine and transcranial direct current stimulation, which have both provided class II evidence, zolpidem, which is also of high quality, and non-invasive stimulation, which appears to be more encouraging than pharmacological therapy. However, heterogeneity is profoundly ingrained in study designs, and only rare schemes have been recommended by authoritative institutions. There is still a lack of an effective clinical protocol for managing patients with DOC following ABI. To advance future clinical studies on DOC, we present a comprehensive review of the progress in clinical identification and management as well as some challenges in the pathophysiology of DOC. We propose a preliminary clinical decision protocol, which could serve as an ideal reference tool for many medical institutions.
Humans ; Transcranial Direct Current Stimulation/methods* ; Consciousness Disorders/etiology* ; Brain Injuries/complications* ; Consciousness ; Neuroimaging

Humans ; Spinal Cord Injuries/complications* ; Paralysis/etiology* ; Nervous System Diseases ; Brain

Vascular damage is followed by vascular endothelial growth factor (VEGF) expression at high levels, which is an important mechanism for cerebral radiation necrosis (CRN) development. Antiangiogenic agents (Bevacizumab) alleviates brain edema symptoms caused by CRN through inhibiting VEGF and acting on vascular tissue around the brain necrosis area. Many studies have confirmed that Bevacizumab effectively relieves symptoms caused by brain necrosis, improves patients' performance status and brain necrosis imaging. Considering that the efficacy of antiangiogenic therapy is mainly related to the duration of drug action, low-dose antiangiogenic agents can achieve favorable efficacy. Prevention is the best treatment. The occurrence of CRN is associated with tumor-related factors and treatment-related factors. By controlling these factors, CRN can be effectively prevented.
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Angiogenesis Inhibitors/pharmacology* ; Bevacizumab/therapeutic use* ; Brain/metabolism* ; Consensus ; Humans ; Lung Neoplasms/drug therapy* ; Necrosis/etiology* ; Radiation Injuries/etiology* ; Vascular Endothelial Growth Factor A/metabolism*

OBJECTIVES: To study the correlation between CT imaging features of acceleration and deceleration brain injury and injury degree. METHODS: A total of 299 cases with acceleration and deceleration brain injury were collected and divided into acceleration brain injury group and deceleration brain injury group according to the injury mechanism. Subarachnoid hemorrhage (SAH) and Glasgow coma scale (GCS), combined with skull fracture, epidural hematoma (EDH), subdural hematoma (SDH) and brain contusion on the same and opposite sides of the stress point were selected as the screening indexes. χ² test was used for primary screening, and binary logistic regression analysis was used for secondary screening. The indexes with the strongest correlation in acceleration and deceleration injury mechanism were selected. RESULTS: χ² test showed that skull fracture and EDH on the same side of the stress point; EDH, SDH and brain contusion on the opposite of the stress point; SAH, GCS were correlated with acceleration and deceleration injury (P<0.05). According to binary logistic regression analysis, the odds ratio (OR) of EDH on the same side of the stress point was 2.697, the OR of brain contusion on the opposite of the stress point was 0.043 and the OR of GCS was 0.238, suggesting there was statistically significant (P<0.05). CONCLUSIONS EDH on the same side of the stress point, brain contusion on the opposite of the stress point and GCS can be used as key indicators to distinguish acceleration and deceleration injury mechanism. In addition, skull fracture on the same side of the stress point, EDH and SDH on the opposite of the stress point and SAH were relatively weak indicators in distinguishing acceleration and deceleration injury mechanism.
Brain Contusion ; Brain Injuries/diagnostic imaging* ; Hematoma, Epidural, Cranial ; Hematoma, Subdural/etiology* ; Humans ; Logistic Models ; Skull Fractures/diagnostic imaging* ; Tomography, X-Ray Computed ; Wounds, Nonpenetrating/diagnostic imaging*

PURPOSE: Hypertonic fluids such as mannitol and half-molar sodium lactate are given to treat intracranial hypertension in patients with severe traumatic brain injury (TBI). In this study, sodium lactate was compared to mannitol in patients with TBI to investigate the efficacy in reducing intracranial pressure (ICP). METHODS: This study was a systematic review with literature research on articles published in any year in the databases of PubMed, ScienceDirect, Asian Journal of Neurosurgery, and Cochrane Central Register of Controlled Trials. The keywords were "half-molar sodium lactate", "mannitol", "cerebral edema or brain swelling", and "severe traumatic brain injury". The inclusion criteria were (1) studies published in English, (2) randomized control trials or retrospective/prospective studies on TBI patients, and (3) therapies including half-molar sodium lactate and mannitol and (4) sufficient data such as mean difference (MD) and risk ratio (RR). Data analysis was conducted using Review Manager 5.3. RESULTS: From 1499 studies, a total of 8 studies were eligible. Mannitol group reduced ICP of 0.65 times (MD 0.65; p = 0.64) and improved cerebral perfusion pressure of 0.61 times (MD 0.61; p = 0.88), better than the half-molar group of sodium lactate. But the half-molar group of sodium lactate maintained the mean arterial pressure level of 0.86 times, better than the mannitol group (MD 0.86; p = 0.09). CONCLUSION Half-molar sodium lactate is as effective as mannitol in reducing ICP in the early phase of brain injury, superior over mannitol in an extended period. It is able to prevent intracranial hypertension and give better brain tissue perfusion as well as more stable hemodynamics. Blood osmolarity is a concern as it increases serum sodium.
Brain Edema ; Brain Injuries, Traumatic/drug therapy* ; Diuretics, Osmotic/therapeutic use* ; Humans ; Intracranial Hypertension/etiology* ; Intracranial Pressure ; Mannitol/therapeutic use* ; Prospective Studies ; Retrospective Studies ; Saline Solution, Hypertonic ; Sodium Lactate

OBJECTIVE: To investigate the effects of blocking the activation of ERK pathway on the expression of matrix metalloproteinase-9 (MMP-9) and the formation of cerebral edema in SD rats after brain injury. METHODS: Ninety SD rats were randomly divided into 3 equal groups, including a sham-operated group, modified Feeney's traumatic brain injury model group, and ERK inhibition group where the ERK inhibitor SCH772984 (500 μg/kg) was injected via the femoral vein 15 min before brain trauma. At 2 h and 2 days after brain trauma, the permeability of blood-brain barrier was assessed by Evans blue method, the water content of the brain tissue was determined, and the phosphorylation level of ERK and the expression level of MMP-9 mRNA and protein were measured by RT-PCR and Western blotting. RESULTS: Compared with the sham-operated group, the rats with brain trauma exhibited significantly increased level of ERK phosphorylation at 2 h and significantly increased expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). Treatment with the ERK inhibitor significantly decreased the phosphorylation level of ERK after the injury ( < 0.01), suppressed over-expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). The permeability of blood-brain barrier increased significantly 2 h after brain trauma ( < 0.05) and increased further at 2 days ( < 0.01); the water content of the brain did not change significantly at 2 h ( > 0.05) but increased significantly 2 d after the injury ( < 0.01). Treatment with the ERK inhibitor significantly lowered the permeability of blood-brain barrier and brain water content after brain trauma ( < 0.01). CONCLUSIONS Blocking the activation of ERK pathway significantly reduced the over-expression of MMP-9 and alleviates the damage of blood-brain barrier and traumatic brain edema, suggesting that ERK signaling pathway plays an important role in traumatic brain edema by regulating the expression of MMP-9.
Animals ; Brain Edema ; drug therapy ; etiology ; Brain Injuries, Traumatic ; complications ; drug therapy ; Gene Expression Regulation, Enzymologic ; drug effects ; Indazoles ; pharmacology ; therapeutic use ; MAP Kinase Signaling System ; drug effects ; Matrix Metalloproteinase 9 ; genetics ; Piperazines ; pharmacology ; therapeutic use ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Objective To discuss the activation characteristics of the prefrontal cortex of people with mild cognitive impairment （MCI） due to brain trauma during working memory tasks. Methods The psychological experiment design software E-prime was used and N-back paradigm was adopted as working memory task. Functional near-infrared spectroscopy （fNIRS） was used to detect changes in cortical oxygenated hemoglobin concentrations of 22 channels within the prefrontal lobe of 24 people with MCI due to brain trauma （study group） and 27 healthy volunteers （control group） with matching gender and age. Behavioral data, such as the number of keystroke errors and reaction time, were recorded simultaneously. Independent samples t test and non-parametric test were used to compare the mean value of oxygenated hemoglobin concentration change, the number of key errors and the mean value of reaction time of the two groups in each task. Results （1） The differences in the number of errors and reaction time between the two groups in 1-back and 2-back tasks had statistical significance （P<0.05）.The main effects of task load and group were both significant （task F=14.11, P=0.001 1; group F=10.39, P=0.001 5）. （2） During the 1-back task, the differences in oxygenated hemoglobin concentration changes of the 22 channels between the two groups had no statistical significance （P>0.05）. During the 2-back task, the differences in oxygenated hemoglobin concentration changes of the two groups in channel 2, 3, 7, 9, 10, 11, 14, 15, 18, 19, 21 and 22 had statistical significance （P<0.05）. （3） In the 1-back task, the left frontal pole and dorsolateral prefrontal area in both groups were activated. In the 2-back task, the activation areas of the control group were the left frontal pole area and the left dorsolateral prefrontal area, while that of the study group almost covered most of the left and right frontal pole areas, which were scattered and the right area was activated, too. Conclusion Patients with MCI due to brain trauma have obvious working memory impairment, and during the 2-back working memory task, the activation of the prefrontal lobe decreased, but the activation range was wider.
Brain Injuries, Traumatic/complications* ; Cognitive Dysfunction/etiology* ; Humans ; Memory, Short-Term ; Prefrontal Cortex ; Spectroscopy, Near-Infrared

Post traumatic epilepsy （PTE） is a serious complication of traumatic brain injury and a difficult problem in forensic justice practice. In recent years, many biomarkers have been applied to the diagnosis, treatment and prognosis of injuries and diseases. There have been many studies on the biomarkers of PTE in the field of epilepsy. This paper reviews the progress in research on biomarkers of PTE in recent years in order to provide reference for the forensic identification of PTE.
Biomarkers/analysis* ; Brain Injuries, Traumatic/diagnosis* ; Epilepsy/etiology* ; Epilepsy, Post-Traumatic/etiology* ; Humans

Objective To explore the applied value of mismatch negative （MMN） in evaluation of severity of mental disorders due to traumatic brain injury. Methods Thirty-five patients（case group） that conform to the diagnostic criteria of organic （traumatic brain injury） mental disorder in ICD-10 Classification of Mental and Behavioural Disorders criteria were selected. Twenty-four healthy subjects （normal control group） that matched the case group in terms of gender, age composition ratio and educational level were selected. All subjects were evaluated by Activity of Daily Living Scale （ADL） and Social Disability Screening Schedule （SDSS） and then examined by Event-Related Potential （ERP）. A statistical analysis of the data was made by SPSS 22.0 software. Results The 32 patients and 24 normal control subjects completed the study. The scores of ADL and SDSS were significantly higher in the case group than in the normal control group （P<0.05）. The latency of Fz, FCz, Cz and Pz in the case group was significantly longer than that in the normal control group （P<0.05）. In the case group, the latency of Fz, FCz, Cz and Pz was positively correlated with the scores of ADL and SDSS （P<0.05）. The equation can be well fitted with the scores of ADL and SDSS. The latency and amplitude of Fz, FCz, Cz and Pz were used as concomitant variables and whether or not the subjects had mental disorders due to traumatic brain injury as dependent variables. Conclusion The latency of MMN can be used as an indicator in potential evaluation of the severity of mental disorders due to traumatic brain injury, which means that the longer the latency of MMN is, the more severe mental disorders due to traumatic brain injury may be. The combined application of ADL, SDSS and MMN can be an objective indicator in preliminary judgment of mental disorders due to traumatic brain injury.
Activities of Daily Living ; Brain Injuries, Traumatic/complications* ; Disabled Persons ; Evoked Potentials ; Humans ; Mental Disorders/etiology* ; Software ; Trauma Severity Indices

Traumatic brain injury (TBI) remains a major cause of death and disability worldwide. Increasing evidence indicates that TBI is an important risk factor for neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and chronic traumatic encephalopathy. Despite improved supportive and rehabilitative care of TBI patients, unfortunately, all late phase clinical trials in TBI have yet to yield a safe and effective neuroprotective treatment. The disappointing clinical trials may be attributed to variability in treatment approaches and heterogeneity of the population of TBI patients as well as a race against time to prevent or reduce inexorable cell death. TBI is not just an acute event but a chronic disease. Among many mechanisms involved in secondary injury after TBI, emerging preclinical studies indicate that posttraumatic prolonged and progressive neuroinflammation is associated with neurodegeneration which may be treatable long after the initiating brain injury. This review provides an overview of recent understanding of neuroinflammation in TBI and preclinical cell-based therapies that target neuroinflammation and promote functional recovery after TBI.
Age Factors ; Animals ; Brain ; immunology ; Brain Injuries, Traumatic ; complications ; therapy ; Cell- and Tissue-Based Therapy ; methods ; Exosomes ; Extracellular Vesicles ; physiology ; Female ; Humans ; Inflammation ; etiology ; Lymphatic System ; physiology ; Male ; Neuroprotective Agents ; Sex Characteristics