Primary Brain Damage Research Articles

Neurosurgical Management of Traumatic Brain Injury

The neurosurgical management of traumatic brain injury (TBI) plays a critical role in ensuring acute survival and mitigating secondary brain damage, which significantly impacts patients' quality of life. TBI is defined as an external force impacting the skull, leading to brain injuries and subsequent functional impairments. It is a leading cause of mortality and morbidity, particularly among young individuals. The initial clinical examination is crucial, with external signs like scalp injuries, hematomas, nasal fluid leakage, skull deformities, and neurological deficits providing important clues to injury patterns. Pupil examination is particularly critical, as mydriasis coupled with reduced consciousness may indicate an acute life-threatening increase in intracranial pressure (ICP), necessitating immediate neurosurgical intervention. TBI assessment often utilizes the Glasgow Coma Scale (GCS), classifying injuries as mild (GCS 13-15), moderate (GCS 9-12), or severe (GCS <9). Even mild TBI can lead to long-term complications. TBI should be viewed as a disease process rather than a singular event. Primary brain damage results from shearing forces on the parenchyma, manifesting as contusions, hematomas, or diffuse axonal injury. Secondary brain damage is driven by mechanisms such as inflammation and spreading depolarizations. Treatment aims not only to secure immediate survival but also to reduce secondary injuries, with ICP management being crucial. Neurosurgical interventions are guided by cranial pathologies, with options including ICP monitoring, burr hole trepanation, craniotomy. In severe TBI cases with refractory ICP elevation, decompressive craniectomy may be performed as a last resort, significantly reducing mortality but often resulting in high morbidity and vegetative states, necessitating careful consideration of indications.

Neuroprotective and neuroregenerative drugs after severe traumatic brain injury : Anarrative review from aclinical perspective.

Traumatic brain injuries cause enormous individual and socioeconomic burdens. Survivors frequently struggle with motor handicaps as well as impaired cognition and emotion. In addition to the primary mechanical brain damage, complex secondary mechanisms are the main drivers of functional impairment. Many of these pathophysiological mechanisms are now well known: excitotoxic amino acids, breakdown of the blood-brain barrier, neuroinflammation with subsequent damage to cell organelles and membranes, cerebral edema, and apoptotic processes triggering neuronal death; however, paracrine resilience factors may counteract these processes. Specific neuroprotective and neuroregenerative intensive care therapies are few. This review highlights medical approaches aimed at mitigating secondary damage and promoting neurotrophic processes in severe traumatic brain injury. Some pharmacologic attempts that appeared very promising in experimental settings have had disappointing clinical results (progesterone, cyclosporineA, ronopterin, erythropoietin, dexanabinol). Thus, the search for drugs that can effectively limit ongoing posttraumatic neurological damage is ongoing. Some medications appear to be beneficial: N‑methyl-D-aspartate receptor (NMDA) antagonists (esketamine, amantadine, Mg++) reduce excitotoxicity and statins and cerebrolysin are known to counteract neuroinflammation. By supporting the impaired mitochondrial energy supply, oxidative processes are inhibited and neuroregenerative processes, such as neurogenesis, angiogenesis and synaptogenesis are promoted by citicoline and cerebrolysin. First clinical evidence shows an improvement in cognitive and thymopsychic outcomes, underlined by own clinical experience combining different therapeutic approaches. Accordingly, adjuvant treatment with neuroprotective substances appears to be apromising option, although more randomized prospective studies are still needed.

Intraoperative application of intelligent, responsive, self-assembling hydrogel rectifies oxygen and energy metabolism in traumatically injured brain

In managing severe traumatic brain injury (TBI), emergency surgery involving the removal of damaged brain tissue and intracerebral hemorrhage is a priority. Secondary brain injury caused by oxidative stress and energy metabolic disorders, triggered by both primary mechanical brain damage and surgical insult, is also a determining factor in the prognosis of TBI. Unfortunately, the effectiveness of traditional postoperative intravenous neuroprotective agents therapy is often limited by the lack of targeting, timeliness, and side effects when neuroprotective agents systemically delivered. Here, we have developed injectable, intelligent, self-assembling hydrogels (P-RT/2DG) that can achieve precise treatment through intraoperative application to the target area. P-RT/2DG hydrogels were prepared by integrating a reactive oxygen species (ROS)-responsive thioketal linker (RT) into polyethylene glycol. By scavenging ROS and releasing 2-deoxyglucose (2DG) during degradation, these hydrogels functioned both in antioxidation and energy metabolism to inhibit the vicious cycle of post-TBI ROS–lactate which provoked secondary injury. In vitro and in vivo tests confirmed the absence of systemic side effects and the neuroprotective function of P-RT/2DG hydrogels in reducing edema, nerve cell apoptosis, neuroinflammation, and maintaining the blood-brain barrier. Our study thus provides a potential treatment strategy with novel hydrogels in TBI.

213.1: Estimating the donor potential in Germany: Systematic evaluation of all in-hospital deaths of patients with primary or secondary brain damage.

213.1: Estimating the donor potential in Germany: Systematic evaluation of all in-hospital deaths of patients with primary or secondary brain damage.

Systemic immune response in young and elderly patients after traumatic brain injury

BackgroundTraumatic brain injury (TBI) is a leading cause of death and long-term disability worldwide. In addition to primary brain damage, systemic immune alterations occur, with evidence for dysregulated immune responses in aggravating TBI outcome and complications. However, immune dysfunction following TBI has been only partially understood, especially in the elderly who represent a substantial proportion of TBI patients and worst outcome. Therefore, we aimed to conduct an in-depth immunological characterization of TBI patients, by evaluating both adaptive (T and B lymphocytes) and innate (NK and monocytes) immune cells of peripheral blood mononuclear cells (PBMC) collected acutely (< 48 h) after TBI in young (18–45 yo) and elderly (> 65 yo) patients, compared to age-matched controls, and also the levels of inflammatory biomarkers.ResultsOur data show that young respond differently than elderly to TBI, highlighting the immune unfavourable status of elderly compared to young patients. While in young only CD4 T lymphocytes are activated by TBI, in elderly both CD4 and CD8 T cells are affected, and are induced to differentiate into subtypes with low cytotoxic activity, such as central memory CD4 T cells and memory precursor effector CD8 T cells. Moreover, TBI enhances the frequency of subsets that have not been previously investigated in TBI, namely the double negative CD27- IgD- and CD38-CD24- B lymphocytes, and CD56dim CD16- NK cells, both in young and elderly patients. TBI reduces the production of pro-inflammatory cytokines TNF-α and IL-6, and the expression of HLA-DM, HLA-DR, CD86/B7-2 in monocytes, suggesting a compromised ability to drive a pro-inflammatory response and to efficiently act as antigen presenting cells.ConclusionsWe described the acute immunological response induced by TBI and its relation with injury severity, which could contribute to pathologic evolution and possibly outcome. The focus on age-related immunological differences could help design specific therapeutic interventions based on patients’ characteristics.

Effect of functional electrical stimulation versus TheraTogs on gait and balance in children with hemiplegic cerebral palsy: a randomized controlled trial

BackgroundChildren with cerebral palsy exhibit postural restrictions and gait problems as a result of both primary and secondary brain damage impairments. One of the main goals of cerebral palsy rehabilitation is to improve gait and balance. As a result, the purpose of this study was to compare the effects of FES and TheraTogs on gait and balance in children with hemiplegic CP. A randomized controlled study was conducted on 30 children with hemiplegic CP (18 boys and 12 girls) between the ages of 8 and 12 years. The children were divided into two equal groups. In addition to the traditional physical treatment program, the FES group received functional electrical stimulation (pulse width 300 μs, frequency 33 Hz, 2 h/day, 3 days/week, 3 months). The TheraTogs group, on the other hand, received the TheraTogs strapping system as well as the same traditional program for the same time period. The 3-D motion analysis and the Biodex balance system were used to analyze gait parameters and postural stability at baseline and 3 months after the intervention.ResultsWhen comparing the mean values of the gait parameters and postural stability indices of children in both groups before and after treatment, a significant improvement was reported. Furthermore, the FES group showed a greater improvement in all of the measured outcomes (P < 0.001).ConclusionFunctional electrical stimulation improves gait pattern and postural stability in children with hemiplegic cerebral palsy significantly more than TheraTogs strapping systems.Clinical trial registrationThis study was registered in the ClinicalTrial.gov PRS (NCT05020834).

MESENCHYMAL STEM CELLS IN THE COMPLEX TREATMENT OF TRAUMATIC BRAIN INJURY

Relevance. The problem of effective prevention and treatment of traumatic brain injuries (TBI) of various etiologies has not been resolved in all countries of the world. Primary brain damage from trauma initiates secondary damage to the nervous tissue. As a result, the interaction of brain neural networks is disrupted and the control of somatic and visceral functions of the body is weakened. The article is based on our own clinical observations and comparison of results with literature data and provides a discussion of the prospects for the use of cell technologies in the prevention of fatal disorders of vital functions control in traumatic brain injuries.&#x0D; Objective. To evaluate the effectiveness of intranasal perineural implantation of mesenchymal stem cells (MSCs) in the complex therapy of patients with TBI.&#x0D; Materials and methods. The technique intranasal perineural administration of MSCs was used in complex therapy of 15 patients with severe TBI. The patients were 19÷69 years old, 13 men and two women. A cell suspension was isolated from the adipose tissue of the patient's abdominal wall and centrifuged for 10 min at 1500 rpm. The cell pellet was washed in phosphate buffered saline and DMEM. Cells were cultured in plastic culture flasks in a humidified atmosphere with 5% CO2 content. The cell mass was trypsinized according to standard technique and resuspended in physiological saline on the day of implantation. Dynamics of culture growth, pluripotency, phenotyping of MSCs were monitored. MSCs were injected under general anesthesia into the submucosa of the nasal cavity 3-4 times with an interval of 3-7 days, depending on the growth rate of MSCs, in a single dose from 12.0×106 to 35.0×106 cells.&#x0D; Results. The use of allogeneic and predominantly autologous MSCs of adipose tissue in the complex treatment of patients with severe TBI by intranasal perineural delivery to the area of traumatic brain injury does not cause complications and is a safe technique. 8 patients with severe TBI showed from 4 to 7 points according to the Glasgow Outcome Scale Extended, with an average of 5.4±1.1 points after 6 months. The main result is that complex therapy, including intranasal implantation of MSCs in acute and subacute periods of severe TBI, contributes to the survival of patients and restoration of neurological – including cognitive – functions control.&#x0D; Conclusions. The effectiveness of intranasal perineural implantation of MSCs in the complex therapy of patients with TBI has been demonstrated. The mechanisms of the beneficial effects of perineural implantation of MSCs in patients with TBI require further research.

Infectious complications of aneurysmal subarachnoid hemorrhage

Objective ‒ to assess the incidence of infectious complications in patients with aneurysmal subarachnoid hemorrhage (SAH); to determine the effect of the complicated course of aneurysmal SAH on the incidence of nosocomial infection.Materials and methods. The results of treatment of 250 patients in the acute period of aneurysmal SAH were analyzed, among them 124 observations (49.6 %) were identified, in which a complicated course of aneurysmal SAH was stated. In 185 cases, endovascular coiling was used to occlude the ruptured aneurysm, and in 65 cases the aneurysm was clipped. A group of patients who underwent infectious complications in the acute period of aneurysmal SAH was identified. The latter included: pneumonia, urinary tract infections, ventriculitis and meningitis.Results. The median age was 48.95 years (range 14 to 74 years). By gender, the majority were women ‒ 144 (57.6 %). Infectious complications were diagnosed in 52 (20.8 %) patients. Pneumonia was noted in 48 (19.2 %) cases. Urinary tract infections were observed in 36 (14.4 %) patients, in 7 (2.8 %) cases, infection of the nervous system (meningitis in 3 cases and ventriculitis in 4 cases). In the group of infectious complications, there were more observations referred to the group of complicated course of aneurysmal SAH ‒ 49 (92.3 %). Patients with severe SAH according to the WFNS, Hunt-Hess scales and the Fisher radiological scale prevailed. The average value was: WFNS ‒ 3.1 and Hunt‒Hess ‒ 3.7, according to the Fisher scale ‒ 3.5. Mortality in the group of infectious complications was 38.5 % (20 cases).Conclusions. Infectious complications occur with a frequency of 20.8 % and are a factor that worsens functional outcome and increases mortality in patients with aneurysmal SAH. Primary brain damage after rupture of an aneurysm, which determines the severity of SAH and the complicated course of the disease, is a predictor of the development of infectious complications.

Neuroprotective effects of flavone luteolin in neuroinflammation and neurotrauma.

Neuroinflammation leads to neurodegeneration, cognitive defects, and neurodegenerative disorders. Neurotrauma/traumatic brain injury (TBI) can cause activation of glial cells, neurons, and neuroimmune cells in the brain to release neuroinflammatory mediators. Neurotrauma leads to immediate primary brain damage (direct damage), neuroinflammatory responses, neuroinflammation, and late secondary brain damage (indirect) through neuroinflammatory mechanism. Secondary brain damage leads to chronic inflammation and the onset and progression of neurodegenerative diseases. Currently, there are no effective and specific therapeutic options to treat these brain damages or neurodegenerative diseases. Flavone luteolin is an important natural polyphenol present in several plants that show anti-inflammatory, antioxidant, anticancer, cytoprotective, and macrophage polarization effects. In this short review article, we have reviewed the neuroprotective effects of luteolin in neurotrauma and neurodegenerative disorders and pathways involved in this mechanism. We have collected data for this study from publications in the PubMed using the keywords luteolin and mast cells, neuroinflammation, neurodegenerative diseases, and TBI. Recent reports suggest that luteolin suppresses systemic and neuroinflammatory responses in Coronavirus disease 2019 (COVID-19). Studies have shown that luteolin exhibits neuroprotective effects through various mechanisms, including suppressing immune cell activation, such as mast cells, and inflammatory mediators released from these cells. In addition, luteolin can suppress neuroinflammatory response, activation of microglia and astrocytes, oxidative stress, neuroinflammation, and the severity of neuroinflammatory diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and TBI pathogenesis. In conclusion, luteolin can improve cognitive decline and enhance neuroprotection in neurodegenerative diseases, TBI, and stroke.

Mast Cell Activation, Neuroinflammation, and Tight Junction Protein Derangement in Acute Traumatic Brain Injury.

Traumatic brain injury (TBI) is one of the major health problems worldwide that causes death or permanent disability through primary and secondary damages in the brain. TBI causes primary brain damage and activates glial cells and immune and inflammatory cells, including mast cells in the brain associated with neuroinflammatory responses that cause secondary brain damage. Though the survival rate and the neurological deficiencies have shown significant improvement in many TBI patients with newer therapeutic options, the underlying pathophysiology of TBI-mediated neuroinflammation, neurodegeneration, and cognitive dysfunctions is understudied. In this study, we analyzed mast cells and neuroinflammation in weight drop-induced TBI. We analyzed mast cell activation by toluidine blue staining, serum chemokine C-C motif ligand 2 (CCL2) level by enzyme-linked immunosorbent assay (ELISA), and proteinase-activated receptor-2 (PAR-2), a mast cell and inflammation-associated protein, vascular endothelial growth factor receptor 2 (VEGFR2), and blood-brain barrier tight junction-associated claudin 5 and Zonula occludens-1 (ZO-1) protein expression in the brains of TBI mice. Mast cell activation and its numbers increased in the brains of 24 h and 72 h TBI when compared with sham control brains without TBI. Mouse brains after TBI show increased CCL2, PAR-2, and VEGFR2 expression and derangement of claudin 5 and ZO-1 expression as compared with sham control brains. TBI can cause mast cell activation, neuroinflammation, and derangement of tight junction proteins associated with increased BBB permeability. We suggest that inhibition of mast cell activation can suppress neuroimmune responses and glial cell activation-associated neuroinflammation and neurodegeneration in TBI.

Multipattern botulinum toxin therapy of post-comatose long-term consciousness disorders: central effects

The data of electroencephalography, evoked potentials of the brain and positron emission tomography are analyzed before and 3 weeks after the multipattern botulinum toxin therapy of spasticity in 25 patients with post-comatose long-term consciousness disorders, including one patient who died against the backdrop gradual improvement of consciousness from acute heart failure four months after the end of second course of multipattern botulinum toxin therapy. Found that improvements of the brain functional state against the backdrop of reduced spasticity were observed regardless of primary brain damage origin, level of consciousness and of multipattern botulinum toxin therapy course repeatability. The observed dynamics of neurophysiological indicators had a normalizing direction, some differences associated with the initial level of consciousness. Electrophysiological changes during the improvement of consciousness against the background of multipattern botulinum toxin therapy were not specific. Features of improving energy metabolism in the certain areas of the brain could be caused by just such treatment, and reflected the contribution of pathological sensorimotor integration in maintaining impaired consciousness. Postmortem neuromorphological study of the patient brain identified progenitor stem and proliferating cells and newly formed neurons in brain areas whose in-life functional state was continuously improving, newly formed neurons migrating flow through the corpus callosum and diffuse activation of axonogenesis. We assume that the central effect of multipattern botulinum toxin therapy associated with improvement of consciousness, may be a double. The first is immediate, due to a decrease in pathological afferentation from the muscles, the second - apparently deferred and prolonged, manifested in the activation of functional neurogenesis and axonogenesis in the brain. The continuation of complex multimodal research on the study of post-comatose long-term consciousness disorders seems promising.

Methodology of registration and reporting of electroencephalogram in unconsciousness patients

A unique feature of electroencephalography (EEG) in patients with primary and secondary brain damage, accompanied by impaired consciousness, is the possibility of reducing the number of recording electrodes and the high frequency of occurrence of stereotypical combinations of graphoelements (special patterns). In EEG reporting in these patients, it is possible to use the special classification developed in 2013, which designates them as “rhythmic and periodic patterns” (RPP). Its implementation significantly increases the degree of inter-rater agreement, and clinical use allows not only to diagnose non-convulsive epileptic status accurately but to predict its occurrence at the preclinical stage and to assess the likelihood of recovery of consciousness in patients with coma. The review outlines the features of EEG recording in unconsciousness patients and describes the reporting methodology of rhythmic and periodic EEG patterns.

Ganglion Cell Topography Indicates Pre- or Postnatal Damage to the Retro-Geniculate Visual System, Predicts Visual Field Function and May Identify Cerebral Visual Impairment in Children – A Multiple Case Study

ABSTRACTIn this paper, we quantify the degree of ganglion cell layer thinning due to retrograde trans-synaptic degeneration (RTSD) from retro-geniculate damage in six cases who had homonymous visual field defects known since childhood. Three had prenatal injuries, occurring close to mid-gestation and in the first parts of the early and late third trimester, respectively, and representing injuries at different early developmental stages. Three had later acquired injuries, at age 1.5, 4 and 13 years. The impact of the injury to the optic radiations was revealed by fibre tractography. The ganglion cell thinning corresponded with the visual field defects and the extent and location of the primary brain damage. The most important sign of RTSD was asymmetry of the ganglion cell topography within the macular area.

Proteomic Analysis and Biochemical Correlates of Mitochondrial Dysfunction after Low-Intensity Primary Blast Exposure.

Service members during military actions or combat training are frequently exposed to primary blasts by weaponry. Most studies have investigated moderate or severe brain injuries from blasts generating overpressures >100 kPa, whereas understanding the pathophysiology of low-intensity blast (LIB)-induced mild traumatic brain injury (mTBI) leading to neurological deficits remains elusive. Our recent studies, using an open-field LIB-induced mTBI mouse model with a peak overpressure at 46.6 kPa, demonstrated behavioral impairments and brain nanoscale damages, notably mitochondrial and axonal ultrastructural changes. In this study, we used tandem mass tagged (TMT) quantitative proteomics and bioinformatics analysis to seek insights into the molecular mechanisms underlying ultrastructural pathology. Changes in global- and phospho-proteomes were determined at 3 and 24 h and at 7 and 30 days post injury (DPI), in order to investigate the biochemical and molecular correlates of mitochondrial dysfunction. Results showed striking dynamic changes in a total of 2216 proteins and 459 phosphorylated proteins at vary time points after blast. Disruption of key canonical pathways included evidence of mitochondrial dysfunction, oxidative stress, axonal/cytoskeletal/synaptic dysregulation, and neurodegeneration. Bioinformatic analysis identified blast-induced trends in networks related to cellular growth/development/movement/assembly and cell-to-cell signaling interactions. With observations of proteomic changes, we found LIB-induced oxidative stress associated with mitochondrial dysfunction mainly at 7 and 30 DPI. These dysfunctions included impaired fission-fusion dynamics, diminished mitophagy, decreased oxidative phosphorylation, and compensated respiration-relevant enzyme activities. Insights on the early pathogenesis of primary LIB-induced brain damage provide a template for further characterization of its chronic effects, identification of potential biomarkers, and targets for intervention.

Validity of clinical examination in screening pediatric minor head trauma with loss of consciousness

Background: Minor head injury is the most common presentation in the emergency room for pediatric cases. Though most of them present with intact consciousness, there is an increased risk of primary and secondary brain damage, owing to several mechanical and cellular pathophysiological changes following trauma. Computed Tomography (CT) is the gold standard diagnostic tool for trauma; however, it has been reported that 30% of CT examinations are unwarranted. This study was carried out to evaluate the diagnostic validity of clinical examination in pediatric minor head trauma.Methods: This cross-sectional study was carried out among 355 patients between 1-15 years of age presenting to the ER, who had closed minor head trauma and loss of consciousness. Patients with GCS of 13-15 were included. A thorough clinical examination including head and neck was carried out. All the participants were subjected to CT examination. Data was entered and analyzed using Microsoft Excel spreadsheet.Results: The prevalence of minor head trauma detected by CT examination was 21.4%. The sensitivity and specificity of clinical examination were 71% and 63.8% respectively. The negative predictive value of the screening test was 89%.Conclusions: The value of clinical examination in detecting minor head trauma may be well complemented by the development of standardized clinical criteria which may be evaluated for its diagnostic capability. Following efficient clinical tool will minimize CT examinations and thereby prevent lethal complications due to radiation overdose in the pediatric population.

The Selective Antagonism of Adenosine A2B Receptors Reduces the Synaptic Failure and Neuronal Death Induced by Oxygen and Glucose Deprivation in Rat CA1 Hippocampus in Vitro.

Ischemia is a multifactorial pathology characterized by different events evolving in time. Immediately after the ischemic insult, primary brain damage is due to the massive increase of extracellular glutamate. Adenosine in the brain increases dramatically during ischemia in concentrations able to stimulate all its receptors, A1, A2A, A2B, and A3. Although adenosine exerts clear neuroprotective effects through A1 receptors during ischemia, the use of selective A1 receptor agonists is hampered by their undesirable peripheral side effects. So far, no evidence is available on the involvement of adenosine A2B receptors in cerebral ischemia. This study explored the role of adenosine A2B receptors on synaptic and cellular responses during oxygen and glucose deprivation (OGD) in the CA1 region of rat hippocampus in vitro. We conducted extracellular recordings of CA1 field excitatory post-synaptic potentials (fEPSPs); the extent of damage on neurons and glia was assessed by immunohistochemistry. Seven min OGD induced anoxic depolarization (AD) in all hippocampal slices tested and completely abolished fEPSPs that did not recover after return to normoxic condition. Seven minutes OGD was applied in the presence of the selective adenosine A2B receptor antagonists MRS1754 (500 nM) or PSB603 (50 nM), separately administered 15 min before, during and 5 min after OGD. Both antagonists were able to prevent or delay the appearance of AD and to modify synaptic responses after OGD, allowing significant recovery of neurotransmission. Adenosine A2B receptor antagonism also counteracted the reduction of neuronal density in CA1 stratum pyramidale, decreased apoptosis at least up to 3 h after the end of OGD, and maintained activated mTOR levels similar to those of controls, thus sparing neurons from the degenerative effects caused by the simil-ischemic conditions. Astrocytes significantly proliferated in CA1 stratum radiatum already 3 h after the end of OGD, possibly due to increased glutamate release. A2Breceptor antagonism significantly prevented astrocyte modifications. Both A2B receptor antagonists did not protect CA1 neurons from the neurodegeneration induced by glutamate application, indicating that the antagonistic effect is upstream of glutamate release. The selective antagonists of the adenosine A2B receptor subtype may thus represent a new class of neuroprotective drugs in ischemia.

BRAIN DERIVED NEUROTROPHIC FACTOR (BDNF) PASCACEDERA KEPALA BERAT SEBAGAI FAKTOR PERAMALAN PERJALANAN PENYAKIT {(Brain Derived Neurotrophic Factor (BDNF) as a Prognostic Factor in Severe Head Injury)}

Severe head Injury result in primary and secondary brain damage. The secondary brain damage produces a more worse effect thanthe primary one. Therefore, the process of the secondary brain damage should be prevented in order to obtain a maximum result ofpatient management. The difficulty is to make sure, whether the secondary brain damage is already very bad or, on the other hand, isstill in a positive condition, causing patient management to have a good result. The prognostic decision, is the most important thing inpatient management. The objective of this research was to find an accurate prognostic factor which is simple and non invasive for severehead injury for each time lapse, 24, 48, 72 and 120 hours after the brain damage which had caused the head injury. The installation ofan intracranial pressure (ICP) monitor for the first 24 hours, after the head injury, followed by taking a cerebrospinal fluid sample forBDNF examination at the first 24 hours, 48 hours, 72 hours and 120 hours as well. Enzyme Linked Immunosorbent Assay was used todetermine BDNF. Each subject was assessed by Glasgow Outcome Scale classification, three months after the injury. The result of thisresearch was that BDNF at 48 hours after head injury showed a significant difference (p &lt; 0.05) between good and bad Glasgow OutcomeScale classification. Thus, it can be concluded that patients with an increase in BDNF (&gt;6.16 pg/mL) 48 hours after head injury, mayhave a good prognosis.

Resolvin D1 Halts Remote Neuroinflammation and Improves Functional Recovery after Focal Brain Damage Via ALX/FPR2 Receptor-Regulated MicroRNAs.

Remote damage is a secondary phenomenon that usually occurs after a primary brain damage in regions that are distant, yet functionally connected, and that is critical for determining the outcomes of several CNS pathologies, including traumatic brain and spinal cord injuries. The understanding of remote damage-associated mechanisms has been mostly achieved in several models of focal brain injury such as the hemicerebellectomy (HCb) experimental paradigm, which helped to identify the involvement of many key players, such as inflammation, oxidative stress, apoptosis and autophagy. Currently, few interventions have been shown to successfully limit the progression of secondary damage events and there is still an unmet need for new therapeutic options. Given the emergence of the novel concept of resolution of inflammation, mediated by the newly identified ω3-derived specialized pro-resolving lipid mediators, such as resolvins, we reported a reduced ability of HCb-injured animals to produce resolvin D1 (RvD1) and an increased expression of its target receptor ALX/FPR2 in remote brain regions. The in vivo administration of RvD1 promoted functional recovery and neuroprotection by reducing the activation of Iba-1+ microglia and GFAP+ astrocytes as well as by impairing inflammatory-induced neuronal cell death in remote regions. These effects were counteracted by intracerebroventricular neutralization of ALX/FPR2, whose activation by RvD1 also down-regulated miR-146b- and miR-219a-1-dependent inflammatory markers. In conclusion, we propose that innovative therapies based on RvD1-ALX/FPR2 axis could be exploited to curtail remote damage and enable neuroprotective effects after acute focal brain damage.

New Challenges: Diagnosis of Brain Death in Newborn, Children and Adolescents

According to the current update of the German guideline on brain death (BD), participation of paediatricians is now mandatory for the examination of BD in patients younger than 14 years. The present analysis focuses on the previous practice and highlights the challenges that arise from the current update. Retrospective evaluation of the patient registry of the German organ procurement organisation (north-eastern bureau) between January, 2001 and December, 2010 with specified paediatric age groups according to the 4th update of the German guideline on BD from the 1st of July 2015. 133 patients (0-17 years) received at least one BD examination. Secondary brain damage was most frequent within the first 6 months of life whereas traumatic and other causes of primary brain damage were predominantly observed thereafter. The number of patients who received BD examination by paediatricians or were treated on neonatal/paediatric intensive care units declined with increasing age. In more than two-third of all paediatric patients, no paediatrician was involved in BD diagnostics. After enforcement of the 4th update of the German guideline on BD, the participation of qualified paediatric physicians must be increased significantly compared to previous practice. Advancements in the specialist training of paediatric physicians, adjustments in patient-centered paediatric care and interdisciplinary diagnostic teams may be solutions to meet this demand.

Rhythmic and periodic EEG patterns. Classification and clinical significance.

The review presents the methodology of electroencephalography (EEG) background analysis, sporadic epileptiform discharges classification, and description of the rhythmic and periodic patterns in patients with primary and secondary brain damage. It describes the process of decision making in starting non-convulsive status epilepticus treatment of patients with EEG-verified non-convulsive status epilepticus and the signs of 'malignant' patterns indicating the irreversibility of brain injury.