Major Brain Injury Research Articles

Atypical resting state neuromagnetic connectivity and spectral power in very preterm children.

Children born very preterm often display selective cognitive difficulties at school age even in the absence of major brain injury. Alterations in neurophysiological activity underpinning such difficulties, as well as their relation to specific aspects of adverse neonatal experience, remain poorly understood. In the present study, we examined interregional connectivity and spectral power in very preterm children at school age, and their relationship with clinical neonatal variables and long-term outcomes (IQ, executive functions, externalizing/internalizing behavior, visual-motor integration). We collected resting state magnetoencephalographic (MEG) and psychometric data from a cohort at the age of 8years followed prospectively since birth, which included three groups: Extremely Low Gestational Age (ELGA, 24-28weeks GA n=24, age 7.7±0.38, 10 girls), Very Low Gestational Age (VLGA, 29-32weeks GA n=37, age 7.7±0.39, 24 girls), and full-term children (38-41weeks GA n=39, age 7.9±1.02, 24 girls). Interregional phase synchrony and spectral power were tested for group differences, and associations with neonatal and outcome variables were examined using mean-centered and behavioral Partial Least Squares (PLS) analyses, respectively. We found greater connectivity in the theta band in the ELGA group compared to VLGA and full-term groups, primarily involving frontal connections. Spectral power analysis demonstrated overall lower power in the ELGA and VLGA compared to full-term group. PLS indicated strong associations between neurophysiological connectivity at school age, adverse neonatal experience and cognitive performance, and behavior. Resting spectral power was associated only with behavioral scores. Our findings indicate significant atypicalities of neuromagnetic brain activity and connectivity in very preterm children at school age, with alterations in connectivity mainly observed only in the ELGA group. We demonstrate a significant relationship between connectivity, adverse neonatal experience, and long-term outcome, indicating that the disruption of developing neurophysiological networks may mediate relationships between neonatal events and cognitive and behavioral difficulties at school age.

Brain structure and neurological and behavioural functioning in infants born preterm.

To examine: (1) relationships between brain structure, and concurrently assessed neurological and behavioural functioning, in infants born preterm at term-equivalent age (TEA; approximately 38-44wks); and (2) whether brain structure-function relationships differ between infants born very (24-29wks) and moderate-late (32-36wks) preterm. A total of 257 infants (91 very preterm, 166 moderate-late preterm; 120 males, 137 females) had structural magnetic resonance imaging (MRI) and neurological and behavioural assessments (Prechtl's general movements assessment, Neonatal Intensive Care Unit Network Neurobehavioral Scale [NNNS] and Hammersmith Neonatal Neurological Examination [HNNE]). Two hundred and sixty-three infants (90 very preterm, 173 moderate-late preterm; 131 males, 132 females) had diffusion MRI and assessments. Associations were investigated between assessment scores and global brain volumes using linear regressions, regional brain volumes using Voxel-Based Morphometry, and white matter microstructure using Tract-Based Spatial Statistics. Suboptimal scores on some assessments were associated with lower fractional anisotropy and/or higher axial, radial, and mean diffusivities in some tracts: NNNS attention and reflexes, and HNNE total score and tone, were associated with the corpus callosum and optic radiation; NNNS quality of movement with the corona radiata; HNNE abnormal signs with several major tracts. Brain structure-function associations generally did not differ between the very and moderate-late preterm groups. White matter microstructural alterations may be associated with suboptimal neurological and behavioural performance in some domains at TEA in infants born preterm. Brain structure-function relationships are similar for infants born very preterm and moderate-late preterm. Brain volume is not related to neurological/behavioural function in infants born preterm at term. White matter microstructure is related to some neurological/behavioural domains at term. Brain-behaviour relationships are generally similar for infants born very preterm and moderate-late preterm.

Outcome after fetoscopic laser coagulation in twin–twin transfusion syndrome – is the survival rate of at least one child at 6 months of age dependent on preoperative cervical length and preterm prelabour rupture of fetal membranes?

Purpose: Twin-to-twin transfusion syndrome (TTTS) complicates 10–15% of all monochorionic twin pregnancies. Selective laser coagulation of placental anastomoses is the only causal therapy. The aim of this study was to analyze the neonatal survival, the survival rate of at least one child at 6 months of age, and maternal outcome after laser therapy in a Swiss cohort.Material and methods: Between 2008 and 2014, 39 women were treated with fetoscopic laser procedure due to TTTS. Two women were excluded from the study because of missing informed consent or loss of follow-up. The women were divided into two groups: group 1 with a cervical length >25 mm and group 2 with a cervical length ≤25 mm. The primary end point was the survival rate of at least one child at 6 months of age and its dependence on maternal preoperative cervical length or the time interval between operation (OP)-preterm prelabour rupture of fetal membranes (PPROM). Secondary outcomes were neonatal complications and maternal complications due to the procedure. Statistical analysis was performed using the program SPSS 22. A p-value of <.05 was considered statistically significant.Results: Mean gestational age (GA) at OP of group 1 (20.3 ± 3 GW) was comparable with group 2 (21.5 ± 2.4 GW; p = .27). The GA at birth was significantly higher in group 1 (31.5 ± 5.9 GW) than in group 2 (27.0 ± 4.7 GW: p = .02). The survival rate of at least one child at 30 days and 6 months of age was 81% in group 1 and only 60% in group 2 (p = .1). PPROM <32 GW occurred in 43%. The survival rate of at least one child was significantly higher if the OP-PPROM interval was >28 days (93 versus 43%; p = .02). Major brain injury was observed in 11% of infants. Severe maternal complications (pulmonary edema) occurred in three cases (8%).Conclusions: Our survival rate of at least one child at 30 days and 6 months of age and the outcome of the mothers is well comparable to other international studies. A preoperative maternal cervical length of >25 mm and an occurrence of PPROM more than 28 days after the laser therapy is associated with a higher survival rate of at least one child at 6 months of age.

Prospective evaluation of the Quality of Life after Brain Injury (QOLIBRI) score: minor differences in patients with major versus no or mild traumatic brain injury at one-year follow up

BackgroundThe Quality of Life after Brain Injury (QOLIBRI) score was developed to assess disease-specific health-related quality of life (HRQoL) after traumatic brain injury (TBI). So far, validation studies on the QOLIBRI were only conducted in cohorts with traumatic brain injury. This study investigated the longer-term residuals in severely injured patients, focusing specifically on the possible impact of major TBI.MethodsIn a prospective questionnaire investigation, 199 survivors with an injury severity score (ISS) > 15 participated in one-year follow-up. Patients who had sustained major TBI (abbreviated injury scale, AIS head > 2) were compared with patients who had no or only mild TBI (AIS head ≤ 2). Univariate analysis (ANOVA, Cohen’s kappa, Pearson’s r) and stepwise linear regression analysis (B with 95% CI, R, R2) were used.ResultsThe total QOLIBRI revealed no differences in one-year outcomes between patients with versus without major TBI (75 and 76, resp.; p = 0.68). With regard to the cognitive subscore, the group with major TBI demonstrated significantly more limitations than the one with no or mild TBI (p < 0.05). The AIS head correlated significantly with the cognitive dimension of the QOLIBRI (r = − 0.16; p < 0.05), but not with the mental components of the SF-36 or the TOP. In multivariate analysis, the influence of the severity of head injury (AIS head) on total QOLIBRI was weaker than that of injured extremities (R2 = 0.02; p < 0.05 vs. R2 = 0.04; p = 0.001) and equal to the QOLIBRI cognitive subscore (R2 = 0.03, p < 0.01 each).ConclusionsGiven the unexpected result of similar mean QOLIBRI total score values and only minor differences in cognitive deficits following major trauma independently of whether patients sustained major brain injury or not, further studies should investigate whether the QOLIBRI actually has the discriminative capacity to detect specific residuals of major TBI. In effect, the score appears to indicate mental deficits following different types of severe trauma, which should be evaluated in more detail.Trial registrationNCT02165137; retrospectively registered 11 June 2014.

Postnatal Brain Growth Assessed by Sequential Cranial Ultrasonography in Infants Born

Brain growth in the early postnatal period following preterm birth has not been well described. This study of infants born at <30 weeks' gestational age and without major brain injury aimed to accomplish the following: 1) assess the reproducibility of linear measures made from cranial ultrasonography, 2) evaluate brain growth using sequential cranial ultrasonography linear measures from birth to term-equivalent age, and 3) explore perinatal predictors of postnatal brain growth. Participants comprised 144 infants born at <30 weeks' gestational age at a single center between January 2011 and December 2013. Infants with major brain injury seen on cranial ultrasonography or congenital or chromosomal abnormalities were excluded. Brain tissue and fluid spaces were measured from cranial ultrasonography performed as part of routine clinical care. Brain growth was assessed in 3 time intervals: <7, 7-27, and >27 days' postnatal age. Data were analyzed using intraclass correlation coefficients and mixed-effects regression. A total of 429 scans were assessed for 144 infants. Several linear measures showed excellent reproducibility. All measures of brain tissue increased with postnatal age, except for the biparietal diameter, which decreased within the first postnatal week and increased thereafter. Gestational age of ≥28 weeks at birth was associated with slower growth of the biparietal diameter and ventricular width compared with gestational age of <28 weeks. Postnatal corticosteroid administration was associated with slower growth of the corpus callosum length, transcerebellar diameter, and vermis height. Sepsis and necrotizing enterocolitis were associated with slower growth of the transcerebellar diameter. Postnatal brain growth in infants born at <30 weeks' gestational age can be evaluated using sequential linear measures made from routine cranial ultrasonography and is associated with perinatal predictors of long-term development.

Occurrence of Major and Minor Brain Injuries in Facial Bone Fractures

Background &amp; objective: Road traffic accident (RTA), now a days, has become a common event worldwide. As face is the most exposed part of the body, is most at risk of sustaining trauma in RTA. However, there is paucity of information regarding the relationship between head injuries and facial trauma. A number of reviews have looked at brain injuries in patients with facial fractures. But these reviews failed to differentiate between major and minor brain injuries. Moreover, most studies were retrospective and based upon large trauma registries, which tend to preselect patients with multiple trauma and capture only major brain injuries. The incidence of minor brain injuries and concussion in this population is thus overlooked. This study was aimed to find the proportion of major and minor brain injuries in patients with facial bone fracture.&#x0D; Materials &amp; Methods: This cross-sectional study was carried out in patients with facial bone fractures who attended at outpatient clinic, hospital ward of the Department of Oral and Maxillofacial Surgery, Dhaka Dental College Hospital, Dhaka, Neurosurgery Department, Emergency Department of Intensive Care Unit of Dhaka Medical College Hospital, Dhaka over a period of 2 years from January 2012 to December 2013. Only the patients of first encounters were included in the study. Patients referred from other centers with facial bone fracture were excluded. A total of 150 such patients were enrolled in the study. To assess and communicate the extent of an unconscious patient’s injury rapidly Glasgow Coma Scale (GCS) was used. The outcome variable was brain injury (major and minor).&#x0D; Result: Majority (80%) of the patients was male with mean age of the patients being 25 years (range: from 4 – 80 years). The most common mechanism of injury in the present study was road-traffic accident (60%), followed by assault (20%), fall from height (12%), crash (6%) and blast trauma (2%). Nearly half (46%) of the patients had multiple facial bone fractures. Over 10% of the patients received Zygomatico-maxillary complex fracture. Mandible fracture and frontal bone fracture each accounted for 7.3%. Nasal bone fracture was 6.7%, isolated maxilla fracture was 5.3%, Le Fort I fracture was 4.7% and orbital floor fracture was 4.0%. The Glasgow coma score 12 or below 12 was found in 52% cases and loss of consciousness and perievent amenesia were observed in 54% and 56% cases respectively. The major and minor brain injuries were found in 52% and 32% cases respectively together comprising an occurrence of 84% in facial bone fractures. Male patients, receiving trauma through RTA and multiple facial bones fractures were significantly associated with brain injury (p = 0.019, p &lt; 0.001, p = 0.001 respectively). However, mandible and nasal bone fractures were less prone to be associated with brain injury in (p = 0.001 and p &lt; 0.001 respectively).&#x0D; Conclusion: The study concluded that majority of the patients with facial bone fractures have had concomitant brain injuries. Male patients, receiving trauma through RTA and multiple fractures of the facial bones are more prone to be associated with brain injury than females, receiving injury through mechanisms other than RTA and isolated facial bone fractures.&#x0D; Ibrahim Card Med J 2016; 6 (1&amp;2): 33-40

Interventions to prevent hypothermia at birth in preterm and/or low birth weight infants.

Interventions to prevent hypothermia at birth in preterm and/or low birth weight infants.

World Academic Council of Emergency Medicine Experience Document: Implementation of Point-of-Care Thromboelastography at an Academic Emergency and Trauma Center.

Background:We aimed to discuss the initial experience of the implementation of point-of-care thromboelastography (POC-TEG) at the Level 1 Trauma Center of an academic health institution in Qatar.Materials and Methods:A TEG protocol was developed and tailored to our hospital requirements and patient population, after an exhausting review of the literature and international published protocols, including a synthesis of a preexisting TEG protocol from our heart hospital. To successfully achieve the incorporation of point-of-care testing (POCT) in our clinical practice, a multidisciplinary organizational and education approach is required. The education and training of the physicians in this POCT modality during the first 3 months period has been described in detail.Results:A TEG protocol has been developed and implemented according to hospital standards. Ten physicians from the department of trauma surgery have been trained over a 3-month period to perform the daily quality control as well as the patient samples in order to provide a 24/7 service. In patients with major trauma, brain injury, bleeding, sepsis, and coagulopathy are the most important determinants of the clinical course and outcomes. Viscoelastic whole-blood assays have already proved their values in cardiac as well as liver surgery. Therefore, this POCT-directed approach would be considered as a part of the goal-directed management in severe polytrauma patients.Conclusions:Our experience shows that implementation of POC-TEG program is feasible and it is a promising tool in the management of major trauma patients with a potential compromised coagulation. However, further prospective research projects and well-trained personnel still warranted.

"Everything Happens in the Hallways": Exploring User Activity in the Corridors at Two Rehabilitation Units.

This research aimed to examine the role of the corridors in specialist inpatient rehabilitation units to inform future design of these spaces. In healthcare settings, such as rehabilitation units, corridors have often been designed simply as spaces allowing movement between other locations. However, research suggests that corridors may be places where important social and care-related activities take place. How corridors are used and understood by patients and staff in inpatient rehabilitation settings is unclear, and a greater understanding of the role of corridors in these settings could help to inform more supportive design of these spaces. Independent observations of user activity were conducted at a major metropolitan inpatient spinal injury unit (SIU) and brain injury unit (BIU). Interviews were conducted with SIU patients ( n = 12), and focus groups were conducted with SIU staff ( n = 23), BIU patients ( n = 12), and BIU staff ( n = 10). Results from the observations showed that the corridors were used frequently across the day, particularly by staff. Thematic analysis of staff and patient experiences found three key themes describing how corridors were used: (1) moving around, (2) delivery and experiences of quality care, and (3) a "spillover space." Results demonstrate that corridors not only have an important role as connective spaces but are also used as flexible, multipurpose spaces for delivery of quality care and patient experiences. Future design should consider how these spaces can more deliberately support and contribute to patient and staff experiences of rehabilitation.

Relationship of mechanical impact magnitude to neurologic dysfunction severity in a rat traumatic brain injury model.

ObjectiveTraumatic brain injury (TBI) is a major brain injury type commonly caused by traffic accidents, falls, violence, or sports injuries. To obtain mechanistic insights about TBI, experimental animal models such as weight-drop-induced TBI in rats have been developed to mimic closed-head injury in humans. However, the relationship between the mechanical impact level and neurological severity following weight-drop-induced TBI remains uncertain. In this study, we comprehensively investigated the relationship between physical impact and graded severity at various weight-drop heights.ApproachThe acceleration, impact force, and displacement during the impact were accurately measured using an accelerometer, a pressure sensor, and a high-speed camera, respectively. In addition, the longitudinal changes in neurological deficits and balance function were investigated at 1, 4, and 7 days post TBI lesion. The inflammatory expression markers tested by Western blot analysis, including glial fibrillary acidic protein, beta-amyloid precursor protein, and bone marrow tyrosine kinase gene in chromosome X, in the frontal cortex, hippocampus, and corpus callosum were investigated at 1 and 7 days post-lesion.ResultsGradations in impact pressure produced progressive degrees of injury severity in the neurological score and balance function. Western blot analysis demonstrated that all inflammatory expression markers were increased at 1 and 7 days post-impact injury when compared to the sham control rats. The severity of neurologic dysfunction and induction in inflammatory markers strongly correlated with the graded mechanical impact levels.ConclusionsWe conclude that the weight-drop-induced TBI model can produce graded brain injury and induction of neurobehavioral deficits and may have translational relevance to developing therapeutic strategies for TBI.

Case-control study demonstrates that surfactant without intubation delayed mechanical ventilation in preterm infants.

This Norwegian study explored whether administering surfactant without intubation (SWI) delayed the need for early mechanical ventilation and reduced respiratory and nonrespiratory complications in infants born before 32 weeks of gestational age. We compared 262 infants admitted to a level-three neonatal intensive care unit: 134 born before the introduction of SWI on 1 December 2011 were in the control group and 128 infants born after this date were in the study group. The proportion of infants treated with surfactant did not differ between the groups, but mechanical ventilation before 72 hours of life was lower in the study group than the control group, with an odds ratio (OR) of 0.58 and a 95% confidence interval (CI) of 0.35-0.96. Fewer study group infants needed supplemental oxygen at 28 days of life. One study infant and nine control infants had intraventricular haemorrhage grades 3-4 and, or, cystic periventricular leukomalacia (OR 0.10, 95% CI 0.01-0.83). These results were strengthened in analyses restricted to surfactant-treated infants and the proportion needing supplemental oxygen at 36 weeks was reduced. Surfactant without intubation reduced the need for early mechanical ventilation and major brain injuries in infants born at <32 weeks of gestation.

Lateral Chronic Cranial Window Preparation Enables In Vivo Observation Following Distal Middle Cerebral Artery Occlusion in Mice.

Focal cerebral ischemia (i.e., ischemic stroke) may cause major brain injury, leading to a severe loss of neuronal function and consequently to a host of motor and cognitive disabilities. Its high prevalence poses a serious health burden, as stroke is among the principal causes of long-term disability and death worldwide1. Recovery of neuronal function is, in most cases, only partial. So far, treatment options are very limited, in particular due to the narrow time window for thrombolysis2,3. Determining methods to accelerate recovery from stroke remains a prime medical goal; however, this has been hampered by insufficient mechanistic insights into the recovery process. Experimental stroke researchers frequently employ rodent models of focal cerebral ischemia. Beyond the acute phase, stroke research is increasingly focused on the sub-acute and chronic phase following cerebral ischemia. Most stroke researchers apply permanent or transient occlusion of the MCA in mice or rats. In patients, occlusions of the MCA are among the most frequent causes of ischemic stroke4. Besides proximal occlusion of the MCA using the filament model, surgical occlusion of the distal MCA is probably the most frequently used model in experimental stroke research5. Occlusion of a distal (to the branching of the lenticulo-striate arteries) MCA branch typically spares the striatum and primarily affects the neocortex. Vessel occlusion can be permanent or transient. High reproducibility of lesion volume and very low mortality rates with respect to the long-term outcome are the main advantages of this model. Here, we demonstrate how to perform a chronic cranial window (CW) preparation lateral to the sagittal sinus, and afterwards how to surgically induce a distal stroke underneath the window using a craniotomy approach. This approach can be applied for sequential imaging of acute and chronic changes following ischemia via epi-illuminating, confocal laser scanning, and two-photon intravital microscopy.

One-year development of QOL following orthopaedic polytrauma: a prospective observational cohort study of 53 patients.

Most studies of polytrauma examined highly mixed patient groups. The objective of the present study was to report the development of patient-reported quality of life (QOL), in a patient group with musculoskeletal polytrauma, excluding patients with major thoracic, abdominal, and brain injuries. The study design was a 1-year cohort follow-up study. Recordings of injury severity were measured with the ISS and NISS. Patient-reported QOL was measured with the questionnaires Eq5d-5L and SF-36 and compared to age-matched reference populations. Moreover, patients return to work status was measured. Data were collected prospectively at discharge, 3, 6, and 12months. 53 patients were included. The mean age was 42.3years, ranging from 17 to 78years. Twelve months after trauma admission, the mean Eq5d-5L index was 0.601 (95% CI 0.546-0.657). A progressive increasing Eq5d-5L index and SF-36 PCS was observed between the discharge and the 12-month follow-up (p<0.001). The development in QOL from 6 to 12 months almost shows identically scores. Throughout the study period, patients reported significant worse QOL compared with the established reference population. 32% of patients have resumed earlier employment status at 1-year follow-up. Throughout the 12-month observational period, patients reported worse QOL compared to the age-matched reference population. The development of QOL from 6- to 12-month time points almost showed identically scores with only little improvement. At the end of 1-year follow-up, 32% of patients had resumed prior employment status.

Highly accurate thermal flow microsensor for continuous and quantitative measurement of cerebral blood flow.

Cerebral blood flow (CBF) plays a critical role in the exchange of nutrients and metabolites at the capillary level and is tightly regulated to meet the metabolic demands of the brain. After major brain injuries, CBF normally decreases and supporting the injured brain with adequate CBF is a mainstay of therapy after traumatic brain injury. Quantitative and localized measurement of CBF is therefore critically important for evaluation of treatment efficacy and also for understanding of cerebral pathophysiology. We present here an improved thermal flow microsensor and its operation which provides higher accuracy compared to existing devices. The flow microsensor consists of three components, two stacked-up thin film resistive elements serving as composite heater/temperature sensor and one remote resistive element for environmental temperature compensation. It operates in constant-temperature mode (~2°C above the medium temperature) providing 20ms temporal resolution. Compared to previous thermal flow microsensor based on self-heating and self-sensing design, the sensor presented provides at least two-fold improvement in accuracy in the range from 0 to 200ml/100g/min. This is mainly achieved by using the stacked-up structure, where the heating and sensing are separated to improve the temperature measurement accuracy by minimization of errors introduced by self-heating.

STAT-dependent upregulation of 12/15-lipoxygenase contributes to neuronal injury after stroke.

Oxidative stress is a major brain injury mechanism after ischemic stroke. 12/15-lipoxygenase (12/15-LOX) is a key mediator of oxidative stress, contributing to neuronal cell death and vascular leakage. Nonetheless, the mechanism leading to its upregulation is currently unknown. We show here that Signal Transducers and Activators of Transcription (STATs), specifically STAT6 and possibly STAT1, increase transcription of 12/15-LOX in neuronal cells. Both p-STAT6 and -1 bound to specific STAT binding sites in the mouse 12/15-LOX promoter. Small interfering RNA (siRNA) knockdown showed STAT6 to be the dominant regulator, reducing 12/15-LOX promoter activation and cell death in oxidatively stressed HT22 cells. STAT6 siRNA efficiently prevented the increase of 12/15-LOX in murine primary neurons, both after induction of oxidative stress and after oxygen-glucose deprivation. Early activation of STAT6 and STAT1 in mice was consistent with a role in regulating 12/15-LOX in focal ischemia. Brains of human stroke patients showed increased p-STAT6 and p-STAT1 in the peri-infarct region, along with 12/15-LOX and markers of apoptosis. These results link STAT6 and STAT1 to the 12/15-LOX damage pathway and suggest disregulation of STAT-dependent transcription as injury mechanism in stroke. Selectively targeting STATs may thus be a novel therapeutic approach to reducing brain injury after a stroke.

Swiss medical centres vary significantly when it comes to outcomes of neonates with a very low gestational age.

AimThis study quantified the impact of perinatal predictors and medical centre on the outcome of very low‐gestational‐age neonates (VLGANs) born at <32 completed weeks in Switzerland.MethodsUsing prospectively collected data from a 10‐year cohort of VLGANs, we developed logistic regression models for three different time points: delivery, NICU admission and seven days of age. The data predicted survival to discharge without severe neonatal morbidity, such as major brain injury, moderate or severe bronchopulmonary dysplasia, retinopathy of prematurity (≥stage three) or necrotising enterocolitis (≥stage three).ResultsFrom 2002 to 2011, 6892 VLGANs were identified: 5854 (85%) of the live‐born infants survived and 84% of the survivors did not have severe neonatal complications. Predictors for adverse outcome at delivery and on NICU admission were low gestational age, low birthweight, male sex, multiple birth, birth defects and lack of antenatal corticosteroids. Proven sepsis was an additional risk factor on day seven of life. The medical centre remained a statistically significant factor at all three time points after adjusting for perinatal predictors.ConclusionAfter adjusting for perinatal factors, the survival of Swiss VLGANs without severe neonatal morbidity was strongly influenced by the medical centre that treated them.

Novel Genes Critical for Hypoxic Preconditioning in Zebrafish Are Regulators of Insulin and Glucose Metabolism.

Severe hypoxia is a common cause of major brain, heart, and kidney injury in adults, children, and newborns. However, mild hypoxia can be protective against later, more severe hypoxia exposure via “hypoxic preconditioning,” a phenomenon that is not yet fully understood. Accordingly, we have established and optimized an embryonic zebrafish model to study hypoxic preconditioning. Using a functional genomic approach, we used this zebrafish model to identify and validate five novel hypoxia-protective genes, including irs2, crtc3, and camk2g2, which have been previously implicated in metabolic regulation. These results extend our understanding of the mechanisms of hypoxic preconditioning and affirm the discovery potential of this novel vertebrate hypoxic stress model.

Protective effects of thrombomodulin on microvascular permeability after subarachnoid hemorrhage in mouse model

The enhanced vascular permeability is a major early brain injury following subarachnoid hemorrhage (SAH). However, its mechanism is not clear yet. In this work, we explored its potential mechanism and investigated the roles of thrombomodulin (TM) in maintaining microvascular integrity after SAH. SAH models were established in adult male ICR mice (28–32g) by endovascular perforation. TM was immediately administered by femoral vein injection following SAH. The brain water content, Evans Blue content and neurological functions were evaluated. Brain edema was also detected by magnetic resonance imaging (MRI) (T2 map). The siRNA technique, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining and western blotting were performed to explore the potential mechanism of TM treatment. The number of microthrombi in the hippocampus microvessels was also recorded. TM significantly decreased brain water content and Evans Blue content, alleviated brain edema and neurological deficits after SAH. The plasma concentration of activated protein C was increased after TM treatment. In addition, the levels of phospho-p38MAPK, phospho-p53, cleaved caspase-3, phospho-NF-κB (p65) were markedly decreased. Additionally, the loss of VE-cadherin and Occludin (markers of vascular integrity) and the number of microthrombi in the hippocampus were also reduced. Our results indicated that TM has protective effects on preserving microvascular integrity following SAH partly through preserving endothelial junction proteins and quenching apoptosis/inflammation in endothelial cells via blocking p38MAPK-p53/NF-κB (p65) pathway.

Differencial Diagnosis of Hypovolemia and Cushing‘s Response in Traumatic Brain Injury Patients, Using Hemodynamic Assessment Methods, to Prevent Secondary Brain Damage

Traumatic brain injury is the leading cause of death and further cause of disability and a major public health problem. Although the severity of the injury depends directly on the primary brain injury, secondary brain injury deteriorates the outcomes. The main causes of secondary ischemic injury include hypotension (systolic blood pressure 90mmHg) and hypoxaemia (PaO260mmHg), which are directly associated with increase of morbidity and mortality due to severe traumatic brain injury. Hypoxia and hypotension during decompresive craniotomy are independently associated with significant increaeses in vegetative state development and higher frequency of disability. Intraoperative period, including immediate anaesthesia during urgent craniotomy, is a critical moment for these patients. Their intraoperative hypotension can be caused by various factors, such as blood loss due other traumatic injuries, direct pulmonary or heart disorders, sympathetic tone lesions (spinal cord injury and neurogenic shock), potent anesthetic medicaments action or current hypovolemia and inadequate infusion therapy. How to solve this situation? Usually we choose a larger infusion therapy and vasoactive drugs. Is it realy a best solution for the patient? Severe brain trauma and related complications are the most common morbidity and mortality causes in young and middle-aged people. The initial injury we can not influence, but to avoid the major secondary brain injury risks, especially such as hypotension and hypoxia, are required. Only quick and accurate diagnosis, secondary risk factors prevention and immediate treatment may improve the outcomes.

S100B concentrations increase perioperatively in jugular vein blood despite limited metabolic and inflammatory response to clinically uneventful carotid endarterectomy.

Our aim was to test the hypothesis that metabolic and inflammatory responses of the brain perioperatively during carotid endarterectomy (CEA) might affect blood brain barrier (BBB) integrity. Twenty patients with >70% stenosis of internal carotid artery (ICA) were prospectively included. Surgery was performed under general anaesthesia. Blood was sampled from ipsilateral internal jugular vein and radial artery: just before, during, and after ICA clamping S100B protein, glucose, lactate, 20 amino acids, and key cytokines were analysed. Jugular vein S100B increased during clamping and reperfusion, while a marginal systemic increase was recorded, unrelated to stump pressure during clamping. Glucose increased during clamping in jugular vein blood and even more systemically, while jugular lactate values were higher than systemic values initially. Most amino acids did not differ significantly between jugular vein and systemic levels: glutamic acid and aspartic acid decreased during surgery while asparagine increased. Jugular vein interleukin (IL)-6 showed a transient non-significant increase during clamping and decreased systemically. IL-8 and IL-10 increased over time. Rising jugular vein S100B concentrations indicated reduced BBB integrity, and marginal secondary increase of S100B systemically. Limited ischaemic effects on the brain during cross-clamping, unrelated to S100B concentrations, were confirmed by lower brain glucose levels and higher lactate levels than in systemic blood. The lack of increased jugular vein glutamic acid disproves any major ischaemic brain injury following CEA. The inflammatory response was limited, did not differ greatly between jugular and systemic blood, and was unrelated to S100B.