Severe Brain Damage Research Articles

A restored humoral environment ameliorates acute brain injury after Angiostrongylus cantonensis infection

Circulating factors in the circulatory system support important functions of living tissues and the body. Parabiosis is a condition in which two living animals are connected using surgical methods and share a single circulatory system. Angiostrongylus cantonensis is the major cause of infectious eosinophilic meningitis, which causes severe damage to the central nervous system (CNS) and immune system. However, the mechanism of immunopathology remains largely unknown. We hypothesize that a restored humoral environment can help relieve damage to the CNS and immune system. In the present study, we found that administration of normal serum significantly reduced mortality, alleviated thymic atrophy and reduced inflammation in the brains of mice infected with A. cantonensis. We further generated parabiotic pairs between two healthy mice, one of which was then orally infected with A. cantonensis. The results showed that compared with singleton mice, mice connected with a healthy parabiotic partner were protected against CNS and immune system damage, as revealed by significantly reduced inflammation in the brain, alleviated thymic atrophy, and decreased expression of proinflammatory cytokines. These findings revealed that a healthy systemic environment can relieve damage to the CNS and immune system in infected mice, suggesting novel therapeutic approaches for diseases involving severe brain and immune system damage.

Neurofilament Light Chain Is a Promising Biomarker in Alcohol Dependence.

Background: Alcohol dependence, a global public health problem, leads to structural and functional damage in the brain. Alcohol dependence patients present complex and varied clinical manifestations and live with general complaints existing in contemporary society, making most people with alcohol dependence hard to identify. Therefore, it is important to find potential biomarkers for the diagnosis and evaluation of alcohol dependence. In the study, we explored potential biomarkers for the diagnosis and monitoring of diseases and evaluated brain structural changes in alcohol dependence patients.Methods: Enzyme-linked immunosorbent assay (ELSA) was employed to detect the expression of serum nucleotide-binding oligomerization domain containing 3 (NLRP3) and single-molecule array (Simoa) assay was used to detect the expression of serum neurofilament light (NfL) in 50 alcohol dependence patients and 50 controls with no drinking history. Alcohol consumption was measured by standard drinks. Neuropsychological assessments, including the Montreal cognitive assessment (MoCA), Pittsburgh sleep quality index (PSQI), generalized anxiety disorder (GAD-7), and patient health questionnaire-9 (PHQ-9), were conducted to evaluate cognitive function and psychological state. The degree of white matter lesions (WMLs) was rated using the Fazekas scale based on magnetic resonance imaging analysis. White matter structure was quantified using the voxel-based morphometry method. The correlations between NLRP3 levels, NfL levels, neuropsychological dysfunction, the degree of WMLs, and white matter volume (WMV) were analyzed in alcohol dependence patients.Results: Serum NLRP3 and NfL levels were higher in the alcohol dependence group. NLRP3 levels were irrelevant to monthly alcohol assumption as well as to the MoCA, PSQI, GAD-7, PHQ-9, and Fazekas scale scores and WMV. NfL levels were positively correlated with the PSQI and PHQ-9 scores as well as the degree of WMLs and negatively correlated with the MoCA scores and WMV. No associations were evident between NfL and monthly alcohol assumption and GAD-7 scores in the alcohol dependence group.Conclusion: This study supports the potential value of serum NfL as a non-invasive biomarker in alcohol dependence. The association with neuropsychological dysfunction and degree of WMLs has implications to use NfL as a promising biomarker to assess the severity of brain damage as well as the progression and prognosis of alcohol dependence.

LEAP MOTION CONTROLLER: THE MOST EFFICIENT TOOL FOR ENHANCING HAND FUNCTIONS

Virtual reality devices, such as the leap motion controller, have been created by the gaming industry for both home and clinical uses. As part of virtual task practice, the leap motion gadget collects and records fine motor abilities of the hand and fingers while controlling a simulated environment that needs coordination. For improved hand function development, it has a more realistic environment design and object tracking. It can also process moving depth using two embedded cameras, providing users with a real-time on-screen hand simulator that is nearly as accurate as genuine hand gestures. The aim of the study is to evaluate the importance of leap motion controller in treatment of various physiotherapeutic disorders. Although the majority of interactive virtual trials have focused on stroke patients, brain development in those with severe and symptomatic brain damage is still normal. Most virtual reality systems are only available to the proximal upper extremities due to the limits of their control mechanisms.

Dose-Dependent Neuroprotective Effects of Bovine Lactoferrin Following Neonatal Hypoxia-Ischemia in the Immature Rat Brain.

Injuries to the developing brain due to hypoxia–ischemia (HI) are common causes of neurological disabilities in preterm babies. HI, with oxygen deprivation to the brain or reduced cerebral blood perfusion due to birth asphyxia, often leads to severe brain damage and sequelae. Injury mechanisms include glutamate excitotoxicity, oxidative stress, blood–brain barrier dysfunction, and exacerbated inflammation. Nutritional intervention is emerging as a therapeutic alternative to prevent and rescue brain from HI injury. Lactoferrin (Lf) is an iron-binding protein present in saliva, tears, and breast milk, which has been shown to have antioxidant, anti-inflammatory and anti-apoptotic properties when administered to mothers as a dietary supplement during pregnancy and/or lactation in preclinical studies of developmental brain injuries. However, despite Lf’s promising neuroprotective effects, there is no established dose. Here, we tested three different doses of dietary maternal Lf supplementation using the postnatal day 3 HI model and evaluated the acute neurochemical damage profile using 1H Magnetic Resonance Spectroscopy (MRS) and long-term microstructure alterations using advanced diffusion imaging (DTI/NODDI) allied to protein expression and histological analysis. Pregnant Wistar rats were fed either control diet or bovine Lf supplemented chow at 0.1, 1, or 10 g/kg/body weight concentration from the last day of pregnancy (embryonic day 21–E21) to weaning. At postnatal day 3 (P3), pups from both sexes had their right common carotid artery permanently occluded and were exposed to 6% oxygen for 30 min. Sham rats had the incision but neither surgery nor hypoxia episode. At P4, MRS was performed on a 9.4 T scanner to obtain the neurochemical profile in the cortex. At P4 and P25, histological analysis and protein expression were assessed in the cortex and hippocampus. Brain volumes and ex vivo microstructural analysis using DTI/NODDI parameters were performed at P25. Acute metabolic disturbance induced in cortical tissue by HIP3 was reversed with all three doses of Lf. However, data obtained from MRS show that Lf neuroprotective effects were modulated by the dose. Through western blotting analysis, we observed that HI pups supplemented with Lf at 0.1 and 1 g/kg were able to counteract glutamatergic excitotoxicity and prevent metabolic failure. When 10 g/kg was administered, we observed reduced brain volumes, increased astrogliosis, and hypomyelination, pointing to detrimental effects of high Lf dose. In conclusion, Lf supplementation attenuates, in a dose-dependent manner, the acute and long-term cerebral injury caused by HI. Lf reached its optimal effects at a dose of 1 g/kg, which pinpoints the need to better understand effects of Lf, the pathways involved and possible harmful effects. These new data reinforce our knowledge regarding neuroprotection in developmental brain injury using Lf through lactation and provide new insights into lactoferrin’s neuroprotection capacities and limitation for immature brains.

Histopathology of brain functional areas in pigs infected by porcine pseudorabies virus

Porcine pseudorabies virus (PRV) infection is a major disease in swine. It is challenging to eradicate the virus entirely after it has invaded Chinese farms, resulting in significant economic losses. This study aimed to explore the histopathological correlation of brain regions in PRV-infected pigs. Twenty pigs were randomly divided into two experimental groups (the PRV-infected and sham-inoculated groups; n = 10 per group). The pigs were then observed for clinical signs at specified time points. Brain tissue samples were collected for histopathological examination on days 3, 10, and 14. The correlation analysis was based on clinical observation, lesion characterization, and pathogen location. Clinical observation showed that the severity of clinical neurological signs increased with time. Pathological dissection and microscopic observation revealed gross pathological changes such as degeneration and necrosis of nerve cells, increase in microglia, eosinophilic inclusion body, lymphocyte infiltration, and loose cortical tissue structure. Immunohistochemistry showed that the virus was mainly localized in neurons, microglia, nerve fibers, cerebellar granular layer, and Purkinje cell layer. The virus invasion route was from the cerebrum to the cerebellum and eventually to the brainstem, and the severity of brain damage increased with time. The route of virus infection was from the olfactory bulb to the hippocampus and eventually to the medulla oblongata, and the viral expression increased with time. Of note, brain injury, viral expression, and clinical neurological signs were positively correlated with the infection period; similarly, the severity and degrees of their changes were positively correlated.

Neurological Deficit and Corrective Effect of Omega-3 Polyunsaturated Fatty Acids in Cerebral Ischemia in Rats: A case-control study

Objectives: It was to assess vasoprotective effects of ω-3 polyunsaturated fatty acids in cerebral ischemia. Materials and methods: The experiments were carried out on 42 male outbred white rats weighing 260 ± 20 g. modeling of cerebral ischemia was carried out under conditions of intravenous thiopental anesthesia (40-50 mg / kg). The studies used models of subtotal, partial and stepwise subtotal cerebral ischemia. The table shows the experimental groups and the number of animals in them. Subtotal cerebral ischemia (SCI) was modeled by simultaneous ligation of both common carotid arteries (CCA). Partial cerebral ischemia (PCI) was modeled by ligating one CCA on the right. Stepwise subtotal CI (SSCI) was performed by sequential ligation of both CCA with an interval of 1 day (subgroup 1), 3 days (subgroup 2), or 7 days (subgroup 3). To study the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFA), animals with CI were injected intragastrically with the drug "Omegamed" (SCI+ω-3 PUFA) at a dose of 5 g / kg body weight for a week. The control group consisted of sham-operated rats of the same sex and weight. Neurological deficits were assessed in the "muscle strength", "swimming test" and "open field" tests after 5-6 hours of the ischemic period. The study was carried out 6 hours after the simulation of the CI. Quantitative continuous data were obtained, which were processed using the licensed computer program Statistica 10.0 for Windows (StatSoft, Inc., USA). Since the experiment used small samples that had an abnormal distribution, the analysis was carried out by methods of nonparametric statistics. Data are presented as Me (LQ; UQ), where Me is the median, LQ is the value of the lower quartile; UQ is the upper quartile value. Differences between groups were considered significant at p <0.05 (Regression Model). Results: With a stepwise bilateral ligation of both common carotid arteries with an interval of 1 day, neurological disorders were most pronounced, which indicates an aggravation of neurological deficit with a reduction in the time between CCA dressings. In rats with SCI, the changes were more pronounced than with PCI, but less than with SCI. The least pronounced changes were noted in the 3rd subgroup (the interval between CCA dressings was 7 days). Studies have shown the dependence of the severity of brain damage in SSCI on the interval between the cessation of blood flow in both CCA. At a 7-day interval between CCA dressings, compensatory mechanisms were activated, which prevented the development of morphological changes and neurological deficits. When CCA was ligated with an interval of 1 day, the degree of neurological deficit was maximal, which indicates insufficient implementation of compensatory mechanisms. Compared with the control group, the rats of the "SCI+ω3-PUFA" group retained neurological deficit, the muscle strength indicator was 86% less (p<0.05), the swimming duration - by 63% (p<0.05), the number of crossed squares - by 55% (p<0.05), the number of washes - by 62% (p<0.05), the number of racks - by 62.5% (p<0.05) and the number of bowel movements - by 60% (p<0.05). However, in comparison with the SCI group, the neurological deficit was less pronounced. There was an increase in muscle strength by 67% (p<0.05), swimming duration by 37.5% (p<0.05) and the number of squares crossed in the open field test by 31% (p<0.05), which indicates the presence of a corrective action in the ω-3 polyunsaturated fatty acids preparation. Conclusion: The introduction of the preparation of ω-3 polyunsaturated fatty acids has a corrective effect in conditions of subtotal cerebral ischemia, contributing to a lesser severity of manifestations of neurological deficit (an increase in muscle strength, duration of swimming and the number of squares crossed in the open field test).

Immunotherapy in Medulloblastoma: Current State of Research, Challenges, and Future Perspectives.

Medulloblastoma (MB), a primary tumor of the central nervous system, is among the most prevalent pediatric neoplasms. The median age of diagnosis is six. Conventional therapies include surgical resection of the tumor with subsequent radiation and chemotherapy. However, these therapies often cause severe brain damage, and still, approximately 75% of pediatric patients relapse within a few years. Because the conventional therapies cause such severe damage, especially in the pediatric developing brain, there is an urgent need for better treatment strategies such as immunotherapy, which over the years has gained accumulating interest. Cancer immunotherapy aims to enhance the body's own immune response to tumors and is already widely used in the clinic, e.g., in the treatment of melanoma and lung cancer. However, little is known about the possible application of immunotherapy in brain cancer. In this review, we will provide an overview of the current consensus on MB classification and the state of in vitro, in vivo, and clinical research concerning immunotherapy in MB. Based on existing evidence, we will especially focus on immune checkpoint inhibition and CAR T-cell therapy. Additionally, we will discuss challenges associated with these immunotherapies and relevant strategies to overcome those.

Effects of Low and High Aneurysmal Wall Shear Stress on Endothelial Cell Behavior: Differences and Similarities.

Background: Intracranial aneurysms (IAs) result from abnormal enlargement of the arterial lumen. IAs are mostly quiescent and asymptomatic, but their rupture leads to severe brain damage or death. As the evolution of IAs is hard to predict and intricates medical decision, it is essential to improve our understanding of their pathophysiology. Wall shear stress (WSS) is proposed to influence IA growth and rupture. In this study, we investigated the effects of low and supra-high aneurysmal WSS on endothelial cells (ECs).Methods: Porcine arterial ECs were exposed for 48 h to defined levels of shear stress (2, 30, or 80 dyne/cm2) using an Ibidi flow apparatus. Immunostaining for CD31 or γ-cytoplasmic actin was performed to outline cell borders or to determine cell architecture. Geometry measurements (cell orientation, area, circularity and aspect ratio) were performed on confocal microscopy images. mRNA was extracted for RNAseq analysis.Results: ECs exposed to low or supra-high aneurysmal WSS were more circular and had a lower aspect ratio than cells exposed to physiological flow. Furthermore, they lost the alignment in the direction of flow observed under physiological conditions. The effects of low WSS on differential gene expression were stronger than those of supra-high WSS. Gene set enrichment analysis highlighted that extracellular matrix proteins, cytoskeletal proteins and more particularly the actin protein family were among the protein classes the most affected by shear stress. Interestingly, most genes showed an opposite regulation under both types of aneurysmal WSS. Immunostainings for γ-cytoplasmic actin suggested a different organization of this cytoskeletal protein between ECs exposed to physiological and both types of aneurysmal WSS.Conclusion: Under both aneurysmal low and supra-high WSS the typical arterial EC morphology molds to a more spherical shape. Whereas low WSS down-regulates the expression of cytoskeletal-related proteins and up-regulates extracellular matrix proteins, supra-high WSS induces opposite changes in gene expression of these protein classes. The differential regulation in EC gene expression observed under various WSS translate into a different organization of the ECs’ architecture. This adaptation of ECs to different aneurysmal WSS conditions may affect vascular remodeling in IAs.

Reactive immunosuppression in stroke patients: The role in neurorehabilitation

There is a close connection between the central nervous system and the immune system. This balance can be impaired in the presence of severe brain damage, i.e. in case of stroke. The consequences of stroke on the balance between these two systems are cerebral inflammation and immunosuppression. The aim of this study is to verify whether lymphopenia may represent a negative prognostic index of functional recovery in the Neurorehabilitative setting.

OC15.05: Increased gamma‐glutamyl transpeptidase as a marker of severe brain damage in CMV‐infected and uninfected fetuses

OC15.05: Increased gamma‐glutamyl transpeptidase as a marker of severe brain damage in CMV‐infected and uninfected fetuses

Miniaturized Electrochemical Sensors to Monitor Fetal Hypoxia and Acidosis in a Pregnant Sheep Model.

Perinatal asphyxia is a major cause of severe brain damage and death. For its prenatal identification, Doppler ultrasound has been used as a surrogate marker of fetal hypoxia. However, Doppler evaluation cannot be performed continuously. We have evaluated the performance of a miniaturized multiparametric sensor aiming to evaluate tissular oxygen and pH changes continuously in an umbilical cord occlusion (UCO) sheep model. The electrochemical sensors were inserted in fetal hindlimb skeletal muscle and electrochemical signals were recorded. Fetal hemodynamic changes and metabolic status were also monitored during the experiment. Additionally, histological assessment of the tissue surrounding the sensors was performed. Both electrochemical sensors detected the pO2 and pH changes induced by the UCO and these changes were correlated with hemodynamic parameters as well as with pH and oxygen content in the blood. Finally, histological assessment revealed no signs of alteration on the same day of insertion. This study provides the first evidence showing the application of miniaturized multiparametric electrochemical sensors detecting changes in oxygen and pH in skeletal muscular tissue in a fetal sheep model.

Persephin as a diagnostic marker of acute brain injury in critically ill newborns: a clinical trial

Aim. To study the correlation of serum persephin with clinical, instrumental and biochemical indicators of brain damage and with an adverse outcome in critically ill newborns.Materials and Methods. The study included 44 critically ill newborns. Blood samples were collected on the 1stand 7thday of life. Brain injury was assessed by recording Apgar score, depression of consciousness and brainstem reflexes in unsedated patients over 7 days of life, convulsions, neurosonographic signs of cerebral edema, serum protein S100B on the 1stand 7thday of life, and using indicators of adverse neurological outcome. The correlation of serum persephin on the 1stand 7thday of life with signs of brain damage was evaluated using the Spearman's rank correlation coefficient and Mann-Whitney U-test.Results. No statistically significant correlation was found between the concentrations of serum persephin on the 1stand 7thday of life and Apgar score (p = 0.721 and 0.222, respectively), depression of consciousness and stem reflexes (p < 0.05), convulsions (p = 0.673 and 0.432, respectively), cerebral edema (p = 0.737 and 0.558, respectively), and serum protein S100B both on the 1stday (p = 0.095 and 0.475, respectively) and 7thday of life (p = 0.988 and p = 0.775, respectively). Further, there was no statistically significant association of the serum persephin on the 1stday of line with an unfavorable outcome (p = 0.294). Yet, we revealed an association of serum persephin on the 7thday of life with an unfavorable outcome (p = 0.013), with a cut-off point of 828 ng/mL, a sensitivity of 39%, and a specificity of 100%.Conclusion. Persephin has poor diagnostic and prognostic significance for assessing the severity of brain damage in critically ill newborns. The obtained data on the correlation of the concentration of persephin for 7 days with an unfavorable outcome are doubtful due to the lack of data on its correlation with signs of severe brain damage.

Application of Diffusion Tensor Imaging in the Evaluation of Brain Injury in Premature Infants with Low and Very Low Birth Weight

Background: Brain injury in premature infants (BIPI) is a severe brain damage in premature infants, resulting in a series of neurological sequelae. Diffusion tensor imaging (DTI), as a magnetic resonance imaging (MRI) technique, is more widely used for premature infants. It is of paramount importance to improve the early diagnosis, treatment, and intervention for this population by using DTI. There are few reports on the application of DTI for the evaluation of BIPI in low-birth-weight (LBW) and very-low-birth-weight (VLBW) infants. Objectives: To analyze the clinical characteristics of BIPI in LBW and VLBW infants and to explore the value of MRI-based DTI in the evaluation of BIPI in LBW infants. Patients and Methods: This prospective study was conducted on 31 cases of BIPI (16 LBW and 15 VLBW infants) and 20 normal control premature infants, undergoing MRI-based DTI at the 37 - 40 weeks corrected gestational age (CGA). Differences in fractional anisotropy (FA) and apparent diffusion coefficient (ADC) between the BIPI and control groups and also between the LBW and VLBW groups with BIPI were analyzed. Also, differences with normal controls in terms of the FA and ADC values were investigated in different brain regions. Results: The FA values in the central white matter of the frontal lobe, central white matter of the occipital lobe, centrum semiovale, posterior limb of the internal capsule (PLIC), and ventral thalamus were significantly lower in the BIPI group as compared to the control group (P < 0.05). The ADCs were lower in the BIPI group compared to the control group, and there was a significant difference (P < 0.05). Comparison of FA and ADC values in the central white matter of the frontal lobe, central white matter of the occipital lobe, centrum semiovale, PLIC, and ventral thalamus did not show any significant differences between the LBW and VLBW groups with BIPI (P > 0.05). Conclusion: The FA and ADC values of DTI can be used for the quantitative evaluation of BIPI in LBW and VLBW infants. The FA value was found to be more accurate than the ADC. Overall, different FA values in different brain areas reflect differences in the brain development of normal premature infants.

EVALUATION OF NEUROLOGICAL DEFICIENCY IN RATS WITH CEREBRAL ISCHEMIA AND ADMINISTRATION OMEGA-3 POLYUNSATURATED FATTY ACIDS

Objectives. It was to assess the degree of neurological deficit in rats with cerebral ischemia and administration of omega-3 polyunsaturated fatty acids. Methods. The experiments were carried out on 42 male outbred white rats weighing 260 ± 20 g. Modeling of cerebral ischemia was carried out under conditions of intravenous thiopental anesthesia (40-50 mg / kg). The studies used models of subtotal, partial and stepwise subtotal cerebral ischemia. The table shows the experimental groups and the number of animals in them. Subtotal cerebral ischemia (SCI) was modeled by simultaneous ligation of both common carotid arteries (CCA). Partial cerebral ischemia (PCI) was modeled by ligating one CCA on the right. Stepwise subtotal CI (SSCI) was performed by sequential ligation of both CCA with an interval of 1 day (subgroup 1), 3 days (subgroup 2), or 7 days (subgroup 3). To study the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFA), animals with CI were injected intragastrically with the drug "Omegamed" (SCI+ω-3 PUFA) at a dose of 5 g / kg body weight for a week. The control group consisted of sham-operated rats of the same sex and weight. Neurological deficits were assessed in the "muscle strength", "swimming test" and "open field" tests after 5-6 hours of the ischemic period. Results. With a stepwise bilateral ligation of both common carotid arteries with an interval of 1 day, neurological disorders were most pronounced, which indicates an aggravation of neurological deficit with a reduction in the time between CCA dressings. In rats with SCI, the changes were more pronounced than with PCI, but less than with SCI. The least pronounced changes were noted in the 3rd subgroup (the interval between CCA dressings was 7 days). Studies have shown the dependence of the severity of brain damage in SSCI on the interval between the cessation of blood flow in both CCA. At a 7-day interval between CCA dressings, compensatory mechanisms were activated, which prevented the development of morphological changes and neurological deficits. When CCA was ligated with an interval of 1 day, the degree of neurological deficit was maximal, which indicates insufficient implementation of compensatory mechanisms. Compared with the control group, the rats of the "SCI+ω3-PUFA" group retained neurological deficit, the muscle strength indicator was 86% less (p<0.05), the swimming duration - by 63% (p<0.05), the number of crossed squares - by 55% (p<0.05), the number of washes - by 62% (p<0.05), the number of racks - by 62.5% (p<0.05) and the number of bowel movements - by 60% (p<0.05). However, in comparison with the SCI group, the neurological deficit was less pronounced. There was an increase in muscle strength by 67% (p<0.05), swimming duration by 37.5% (p<0.05) and the number of squares crossed in the open field test by 31% (p<0.05), which indicates the presence of a corrective action in the ω3-PUFA preparation. Conclusion. The introduction of the preparation of ω-3 polyunsaturated fatty acids has a corrective effect in conditions of subtotal cerebral ischemia, contributing to a lesser severity of manifestations of neurological deficit (an increase in muscle strength, duration of swimming and the number of squares crossed in the open field test). Key words: cerebral ischemia, rats, neurological deficiency, omega-3 polyunsaturated fatty acids.

Quantification of the effectivity of laser therapy shortly following brain injury via dual-wavelength laser imaging

Treatment of traumatic brain injury, within a few minutes and even before transportation to the nearest medical facility, can significantly curtail injury severity and even prevent death. The primary aim of this study was to evaluate the effect of laser irradiation as a therapeutic intervention tool immediately following brain injury. To this end, a dual-wavelength laser speckle contrast imaging (DW-LSCI) system based on two laser sources at two wavelengths 532 and 660 nm was employed to monitor changes in cerebral blood flow, tissue saturation and rate of oxygen consumption in a mouse model of intact head injury. In addition, structural changes of tissue were evaluated using linear approximation to Rayleigh-MIE scattering in the range between the two laser wavelengths. Furthermore, cerebral tissue temperature was imaged by a thermal camera providing additional information on physiological brain tissue condition. Experiments were conducted on anesthetized mice (n = 6, female) subjected to a closed head weight-drop model of focal brain injury. After 5 min of baseline measurement, focal brain injury was induced and measurements were conducted for 10 min. Low-level laser therapy (LLLT) was than administrated for a duration of 15 min with uniform exposure of 45 J/cm2 from a CW diode laser source (810 nm). Concurrently, measurements were carried out over the treatment time interval. Laser illumination was then blocked and measurements continued for another 20 min, followed by euthanasia. In comparison to baseline measurements, noticeable variations were revealed post-injury which indicate the severity of brain damage. The use of LLLT inhibited the development of complications in the injured mice by increasing blood flow and saturation and overall oxygen consumption level over the injured area which highlights its effectiveness as a neuroprotective agent immediately following brain injury. Different doses of low-level laser irradiation were also tested (n = 12) with less effectiveness on cerebral parameters. The results presented here support our hypothesis that a high dose of laser irradiation as a first aid can attenuate the injury and save the brain from further worse outcome. To the best of our knowledge, the implementation of the DW-LSCI system to monitor brain hemodynamic and metabolic response to LLLT shortly after head injury in intact mouse brain has not been previously reported.

ПРИМЕНЕНИЕ НОВЫХ МЕТОДИК ПРИ ЛЕЧЕНИИ ПОСТРАДАВШИХ С ПЕРЕЛОМАМИ ДЛИННЫХ ТРУБЧАТЫХ КОСТЕЙ ПРИ ТЯЖЁЛОЙ СОЧЕТАННОЙ ТРАВМЕ

Severe combined injuries, and especially polytrauma, differ significantly from other types of injuries by high requirements for the organization of medical care at all its stages, miltidisciplinarity, high financial costs, poor short-term outcomes and long-term treatment results. Therefore, the search for new concepts, strategies and tactics for the treatment of victims is an urgent problem not only for surgeons, resuscitators and traumatologists, but also for healthcare in general. Fractures of long tubular bones accompanying severe combined injuries or polytrauma pose a lesser threat to the life of the victim than severe traumatic brain injuries or damage to internal organs, but they are the main cause of long-term treatment and disability. Such victims make up a significant group of patients-66.2%, therefore they represent a separate problem in traumatology and injury surgery. A modern solution to this problem, improving the results of treatment and the quality of life of victims after suffering a severe combined injury or polytrauma is possible on the basis of new approaches, as well as on the new ideology of osteosynthesis. In the present study, 392 minimally invasive osteosyntheses were performed in 274 patients with severe combined trauma and polytrauma. The indication was the need to fix fractures in order to create favorable conditions for rapid and lasting fusion, early functional treatment and rehabilitation of victims, and to achieve the highest possible level of quality of life after treatment. The possibility and duration of osteosynthesis were determined by the severity of the condition of the victims, assessed by objective methods: a simple clinical scale of VPH-SG or, much less often, specialized resuscitation scales of VPH-SS, SAPS or MODS. The surgical intervention was possible when the severity of the victim's condition reached the highest level of compensation: 16-30 points on the VPH-SG scale. The immediate outcomes of treatment of 274 patients with severe combined trauma and polytrauma after performing a full and final volume of surgery were good. There were no fatal outcomes. The frequency of mild local infectious complications in the field of surgical intervention was 4.0%. The average duration of inpatient treatment was 23.8±2.3 days: with closed intramedullary osteosynthesis - 19.8±0.3 days, with bone osteosynthesis - 24.2±1.2 days, with non - focal osteosynthesis-27.3±1.9 days. The long-term and anatomical and functional results of treatment were analyzed in 158 patients. There were no unsatisfactory long-term results of treatment. Good long-term results were achieved in 81.0%, satisfactory – in 19.0% of the victims. Thus, the results of the analysis of the immediate outcomes and long-term results of treatment of fractures of long tubular bones using the technology of minimally invasive osteosynthesis in patients with severe combined trauma and polytrauma demonstrated the high effectiveness of this surgical technology, on the one hand, and the direct dependence of the treatment outcomes on the severity of the injuries, the severity of the condition of the victims and the number of fractures in one victim, on the other hand.

Clinical Ethics and Disorder of Consciousness

"Disorders of Consciousness (DOCs) identify a diverse group of dysfunctions affecting individuals who have survived severe brain damage. Although the clinical evaluation of patients with DOC normally depends on their residual ability to create a connection with the outside world through motor behavior, in the last ten years neuroscientists have made a great effort to better characterize the patient’s consciousness even in the case of reduced or no motor reactivity. Often, in fact, patients with DOCs are not able to perform any type of movement or adequately understand the command required but they might be still conscious or at least minimally conscious. The gap between patients’ motor capability and their residual brain complexity raises important moral issues, especially about appropriateness and proportionality of interventions and treatments. We argue that Clinical Ethics Consultation may be crucial in addressing these clinical scenarios, which assume aspects of further drama when the DOC derives from a sudden and unexpected acute event such as a trauma or a cerebrovascular accident in healthy patients. In these situations, given the particular vulnerability of the patients and the unpredictability of the diseases, Ethics Consultants should be involved in the therapeutic process in order to improve the standard of care, ensuring compliance with the inclinations and desires of the patients. Moreover, Ethics Consultants should monitor that the procedures are rigorously managed in the context of fully understood consent of those who are legally entitled to make decision. "

Aberrant gut-microbiota-immune-brain axis development in premature neonates with brain damage

SummaryPremature infants are at substantial risk for suffering from perinatal white matter injury. Though the gut microbiota has been implicated in early-life development, a detailed understanding of the gut-microbiota-immune-brain axis in premature neonates is lacking. Here, we profiled the gut microbiota, immunological, and neurophysiological development of 60 extremely premature infants, which received standard hospital care including antibiotics and probiotics. We found that maturation of electrocortical activity is suppressed in infants with severe brain damage. This is accompanied by elevated γδ T cell levels and increased T cell secretion of vascular endothelial growth factor and reduced secretion of neuroprotectants. Notably, Klebsiella overgrowth in the gut is highly predictive for brain damage and is associated with a pro-inflammatory immunological tone. These results suggest that aberrant development of the gut-microbiota-immune-brain axis may drive or exacerbate brain injury in extremely premature neonates and represents a promising target for novel intervention strategies.

Vasoprotective Effects of Omega-3 Polyunsaturated Fatty Acids in Cerebral Ischemia

Objective: It was to assess vasoprotective effects of ω-3 polyunsaturated fatty acids in cerebral ischemia. Methods: The experiments were carried out on 42 male outbred white rats weighing 260 ± 20 g. Modeling of cerebral ischemia was carried out under conditions of intravenous thiopental anesthesia (40-50 mg/kg). The studies used models of subtotal, partial and stepwise subtotal cerebral ischemia. The table shows the experimental groups and the number of animals in them. Subtotal cerebral ischemia (SCI) was modeled by simultaneous ligation of both common carotid arteries (CCA). Partial cerebral ischemia (PCI) was modeled by ligating one CCA on the right. Stepwise subtotal CI (SSCI) was performed by sequential ligation of both CCA with an interval of 1 day (subgroup 1), 3 days (subgroup 2), or 7 days (subgroup 3). To study the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFA), animals with CI were injected intragastrically with the drug “Omegamed” (SCI+ω-3 PUFA) at a dose of 5g/kg body weight for a week. The control group consisted of sham-operated rats of the same sex and weight. Neurological deficits were assessed in the “muscle strength”, “swimming test” and “open field” tests after 5-6 hours of the ischemic period. Results: With a stepwise bilateral ligation of both common carotid arteries with an interval of 1 day, neurological disorders were most pronounced, which indicates an aggravation of neurological deficit with a reduction in the time between CCA dressings. In rats with SCI, the changes were more pronounced than with PCI, but less than with SCI. The least pronounced changes were noted in the 3rd subgroup (the interval between CCA dressings was 7 days). Studies have shown the dependence of the severity of brain damage in SSCI on the interval between the cessation of blood flow in both CCA. At a 7-day interval between CCA dressings, compensatory mechanisms were activated, which prevented the development of morphological changes and neurological deficits. When CCA was ligated with an interval of 1 day, the degree of neurological deficit was maximal, which indicates insufficient implementation of compensatory mechanisms. Compared with the control group, the rats of the “SCI+ω3-PUFA” group retained neurological deficit, the muscle strength indicator was 86% less (p<0.05), the swimming duration - by 63% (p<0.05), the number of crossed squares - by 55% (p<0.05), the number of washes - by 62% (p<0.05), the number of racks - by 62.5% (p<0.05) and the number of bowel movements - by 60% (p<0.05). However, in comparison with the SCI group, the neurological deficit was less pronounced. There was an increase in muscle strength by 67% (p<0.05), swimming duration by 37.5% (p<0.05) and the number of squares crossed in the open field test by 31% (p<0.05), which indicates the presence of a corrective action in the ω-3 polyunsaturated fatty acids preparation. Conclusion The introduction of the preparation of ω-3 polyunsaturated fatty acids has a corrective effect in conditions of subtotal cerebral ischemia, contributing to a lesser severity of manifestations of neurological deficit (an increase in muscle strength, duration of swimming and the number of squares crossed in the open field test).

Magnetic Resonance Image of Neonatal Acute Bilirubin Encephalopathy: A Diffusion Kurtosis Imaging Study.

Background and Objective: The abnormal T1-weighted imaging of MRI can be used to characterize neonatal acute bilirubin encephalopathy (ABE) in newborns, but has limited use in evaluating the severity and prognosis of ABE. This study aims to assess the value of diffusion kurtosis imaging (DKI) in detecting ABE and understanding its pathogenesis.Method: Seventy-six newborns with hyperbilirubinemia were grouped into three groups (mild group, moderate group, and severe group) based on serum bilirubin levels. All the patients underwent conventional MRI and DKI serial, as well as 40 healthy full-term infants (control group). The regions of interest (ROIs) were the bilateral globus pallidus, dorsal thalamus, frontal lobe, auditory radiation, superior temporal gyrus, substantia nigra, hippocampus, putamen, and inferior olivary nucleus. The values of mean diffusivity (MD), axial kurtosis (AK), radial kurtosis (RK), and mean kurtosis (MK), and fractional anisotropy (FA), radial diffusivity (RD), and axis diffusivity (AD) of the ROIs were evaluated. All newborns were followed up and evaluated using the Denver Development Screening Test (DDST). According to the follow-up results, the patients were divided into the normal group, the suspicious abnormal group, and the abnormal group.Result: Compared with the control group, significant differences were observed with the increased MK of dorsal thalamus, AD of globus pallidus in the moderate group, and increased RD, MK, AK, and RK value of globus pallidus, dorsal thalamus, auditory radiation, superior temporal gyrus, and hippocampus in the severe group. The peak value of total serum bilirubin was moderately correlated with the MK of globus pallidus, dorsal thalamus, and auditory radiation and was positively correlated with the other kurtosis value. Out of 76 patients, 40 finished the DDST, and only 9 patients showed an abnormality. Compared with the normal group, the AK value of inferior olivary nucleus showed significant differences (p < 0.05) in the suspicious abnormal group, and the MK of globus pallidus, temporal gyrus, and auditory radiation; RK of globus pallidus, dorsal thalamus, and auditory radiation; and MD of globus pallidus showed significant differences (p < 0.05) in the abnormal group.Conclusion: DKI can reflect the subtle structural changes of neonatal ABE, and MK is a sensitive indicator to indicate the severity of brain damage.