Brain In Relation Research Articles

Guidelines and standards for the study of death and recalled experiences of death--a multidisciplinary consensus statement and proposed future directions.

An inadvertent consequence of advances in stem cell research, neuroscience, and resuscitation science has been to enable scientific insights regarding what happens to the human brain in relation to death. The scientific exploration of death is in large part possible due to the recognition that brain cells are more resilient to the effects of anoxia than assumed. Hence, brain cells become irreversibly damaged and "die" over hours to days postmortem. Resuscitation science has enabled life to be restored to millions of people after their hearts had stopped. These survivors have described a unique set of recollections in relation to death that appear universal. We review the literature, with a focus on death, the recalled experiences in relation to cardiac arrest, post-intensive care syndrome, and related phenomena that provide insights into potential mechanisms, ethical implications, and methodologic considerations for systematic investigation. We also identify issues and controversies related to the study of consciousness and the recalled experience of cardiac arrest and death in subjects who have been in a coma, with a view to standardize and facilitate future research.

Comparative analysis of brain in relation to the body length and weight of common carp (Cyprinus carpio) in captive (hatchery) and wild (river system) populations.

Cyprinus carpio is the member of family cyprinidae commonly called common carp. This study was aimed to find out the comparison of brain of wild (river system) and captive (hatchery reared) population of common carp. A total of thirty samples (15 from hatchery and 15 from river Swat) were collected. All the specimens were examined in Laboratory of Parasitoloy, Zoology Department, University of Malakand. Findings indicated that wild population were greater in brain size and weight as compared to hatchery reared population. The fish samples collected from captive environment (hatchery) were showing more weight and length as compared to wild population of common carps. The mean value of total weight of hatchery fishes 345±48.68 and the mean value of brain weight of hatchery reared fishes 0.28±0.047. The mean value of wild fish's total body weight 195.16±52.58 and the mean value of brain weight of wild fishes are 0.45±0.14. Present research calls for the fact that fish in dependent environmental conditions possess brain larger in size as compared to its captive population, it is due to use and disuse of brain in their environmental requirements.

Postpartum Gray Matter Changes in the Auditory Cortex.

After giving birth, a mother’s brain undergoes functional adaptations fostering the ability to properly respond to the needs of her newborn. Tuning into and understanding her baby’s crying is among the top skills required and executed in the early stages of motherhood. However, surprisingly little is known about potential changes in the anatomy of the maternal auditory cortex. Therefore, in this longitudinal study, we compared the brains of 14 healthy women between immediate postpartum (within 1–2 days of childbirth) and late postpartum (at 4–6 weeks after childbirth), focusing on areas of the primary, secondary, and higher auditory cortex. We observed significant volume increases within all auditory regions and subregions examined, which might reflect rapid adaptations of the mother’s brain in relation to reliably interpreting her newborn’s cries. There was also a trend for a larger postpartum increase within right-hemispheric regions compared to left-hemispheric regions that might be specifically linked to the ability to discern the pitch, sound, and volume of a baby’s crying. Follow-up research is warranted to replicate these findings and evaluate their current interpretation.

ITVT-03. Use of Functional MRI and DTI for Surgical Planning of Maximal Extent of Resection of CNS Tumors - A Single Neurosurgical Center’s Experience

Abstract Use of functional neuroimaging capabilities such as fMRI, DTI, MRP, MRS, AS-PET-CT, SPECT, and TMS as noninvasive tools to visualize intrinsic brain and spine morphology in relation to function have developed over the past 30 years. Amongst these imaging modalities, functional magnetic resonance imaging (fMRI) is of particular interest since it follows the physiological coupling between neuronal electrical activity and metabolic structural (cellular) activity as it relates to tissue vascularity and perfusion states. As an adjunct to this modality, MRI-based diffusion tensor imaging (DTI) allows further detailed radiographic assessment of fiber tracts in the brain in relationship to the surgical lesion of interest. In addition, combination of other imaging modalities including MR perfusion and intraoperative tools such as neuronavigation and direct cortical stimulation can help guide the extent of maximal safe resection. Herein we present a case series from our neurosurgical institution of primary intra-axial, extra-axial, supratentorial, and brainstem tumors resected using fMRI and DTI for presurgical planning allowing for maximal safe extent of resection and outcomes.

Human Brain and Blood N-Glycome Profiling in Alzheimer's Disease and Alzheimer's Disease-Related Dementias.

Glycosylation, the process of adding glycans (i.e., sugars) to proteins, is the most abundant post-translational modification. N-glycosylation is the most common form of glycosylation, and the N-glycan moieties play key roles in regulating protein functions and many other biological processes. Thus, identification and quantification of N-glycome (complete repertoire of all N-glycans in a sample) may provide new sources of biomarkers and shed light on health and disease. To date, little is known about the role of altered N-glycome in Alzheimer’s Disease and Alzheimer’s Disease-related Dementias (AD/ADRD). The current study included 45 older adults who had no cognitive impairment (NCI) at baseline, followed and examined annually, and underwent brain autopsy after death. During about 12-year follow-up, 15 developed mild cognitive impairment (MCI), 15 developed AD, and 15 remained NCI. Relative abundances of N-glycans in serum at 2 time points (baseline and proximate to death, ∼12.3 years apart) and postmortem brain tissue (dorsolateral prefrontal cortex) were quantified using MALDI-TOF-MS. Regression models were used to test the associations of N-glycans with AD/ADRD phenotypes. We detected 71 serum and 141 brain N-glycans, of which 46 were in common. Most serum N-glycans had mean fold changes less than one between baseline and proximate to death. The cross-tissue N-glycan correlations were weak. Baseline serum N-glycans were more strongly associated with AD/ADRD compared to change in serum N-glycans over time and brain N-glycans. The N-glycan associations were observed in both AD and non-AD neuropathologies. To our knowledge, this is the first comprehensive glycomic analysis in both blood and brain in relation to AD pathology. Our results suggest that altered N-glycans may serve as mechanistic biomarkers for early diagnosis and progression of AD/ADRD.

The hallmarks of environmental issues and the brain

BACKGROUND AND AIM: The aim of this presentation is to discuss the knowledge regarding the impact of the hallmark environmental insults on the brain. Air pollution, noise, heat, light at night, industrial chemicals, and lack of green space have been associated with the impairment of brain development and function and higher risk of neurological diseases and neurodegeneration. METHODS: Several hallmarks (oxidative stress, methylation, endocrine disruption, mitochondrial disfunction, telomers, intravesicular cells, miRNA, microbiome, autonomous nervous system irritation) have been suggested to underline these relationships via direct and indirect pathways. The nervous system itself controls the body's physiological processes and as such could impair the cardiovascular, metabolic/endocrine, and respiratory systems, among others. RESULTS:The efforts in understanding the intermediate role of the cellular hallmarks between the exposure and the brain effects is a path to establish causal relationships. For instance, a key development is to discover the windows of greatest sensitivity of structural and functional brain changes to air pollution. The brain has the widest vulnerable window among all systems. Prenatal exposures may have more severe consequences for the brain because brain structures are forming during this period and may cause permanent brain injury and predict cognitive impairment later in life. Supporting the importance of the prenatal period, mice experiments consistently reported that prenatal exposure to fine PM and diesel exhaust could induce inflammatory reactions and structural changes in several brain regions related with the myelination process which has been replicated in humans, in part, through impairing placental function via PM deposition in the placenta or indirectly via several of the hallmarks in peripheral blood and in the placenta itself. CONCLUSIONS:Hallmarks could be relevant for informing about the persistence or tracking of the effects until later life. It is important to simultaneously study the effect of these hallmarks together on the brain in relation to the exposome. KEYWORDS: omics technologies,Neurologic and mental health outcomes, air pollution, chemical exposues, climate

PPAR Gamma and Viral Infections of the Brain

Peroxisome Proliferator-Activated Receptor gamma (PPARγ) is a master regulator of metabolism, adipogenesis, inflammation and cell cycle, and it has been extensively studied in the brain in relation to inflammation or neurodegeneration. Little is known however about its role in viral infections of the brain parenchyma, although they represent the most frequent cause of encephalitis and are a major threat for the developing brain. Specific to viral infections is the ability to subvert signaling pathways of the host cell to ensure virus replication and spreading, as deleterious as the consequences may be for the host. In this respect, the pleiotropic role of PPARγ makes it a critical target of infection. This review aims to provide an update on the role of PPARγ in viral infections of the brain. Recent studies have highlighted the involvement of PPARγ in brain or neural cells infected by immunodeficiency virus 1, Zika virus, or human cytomegalovirus. They have provided a better understanding on PPARγ functions in the infected brain, and revealed that it can be a double-edged sword with respect to inflammation, viral replication, or neuronogenesis. They unraveled new roles of PPARγ in health and disease and could possibly help designing new therapeutic strategies.

Investigating morphological changes in the brain in relation to etiology and duration of olfactory dysfunction with voxel-based morphometry

Olfactory loss (OL) affects up to 20% of the general population and is related to changes in olfaction-related brain regions. This study investigated the effect of etiology and duration of OL on gray matter volume (GMV) of these regions in 257 patients. Voxel-based morphometry was applied to measure GMV in brain regions of interest to test the effects of etiology and duration on regional GMV and the relation between olfactory function and regional GMV. Etiology of OL had a significant effect on GMV in clusters representing the gyrus rectus and orbitofrontal cortex (OFC), bilaterally. Patients with congenital anosmia had reduced GMV in the gyrus rectus and an increased OFC volume compared to patients with acquired OL. There was a significant association between volume of the left OFC and olfactory function. This implies that changes in GMV in patients with acquired OL are mainly reflected in the OFC and depend on olfactory function. Morphology of olfactory areas in the brain therefore seems to relate to olfactory function and the subsequent degree of exposure to olfactory input in patients with acquired OL. Differences in GMV in congenital anosmia are most likely due to the fact that patients were never able to smell.

Spatial Mapping of Distributed Sensors Biomimicking the Human Vision System

Machine vision has been thoroughly studied in the past, but research thus far has lacked an engineering perspective on human vision. This paper addresses the observed and hypothetical neural behavior of the brain in relation to the visual system. In a human vision system, visual data are collected by photoreceptors in the eye, and these data are then transmitted to the rear of the brain for processing. There are millions of retinal photoreceptors of various types, and their signals must be unscrambled by the brain after they are carried through the optic nerves. This work is a forward step toward explaining how the photoreceptor locations and proximities are resolved by the brain. It is illustrated here that unlike in digital image sensors, there is no one-to-one sensor-to-processor identifier in the human vision system. Instead, the brain must go through an iterative learning process to identify the spatial locations of the photosensors in the retina. This involves a process called synaptic pruning, which can be simulated by a memristor-like component in a learning circuit model. The simulations and proposed mathematical models in this study provide a technique that can be extrapolated to create spatial distributions of networked sensors without a central observer or location knowledge base. Through the mapping technique, the retinal space with known configuration generates signals as scrambled data-feed to the logical space in the brain. This scrambled response is then reverse-engineered to map the logical space’s connectivity with the retinal space locations.

MO445BRAIN AND GUT AXIS IN CHRONIC KIDNEY DISEASE: FOCUS ON SPECIFIC BIOMARKERS, AND TIGHT JUNCTION PROTEINS

Abstract Background and Aims Chronic kidney disease (CKD) is a progressive systemic disease that affect the microvascular permeability of the blood-brain barrier (BBB) and intestinal barrier leading to increased morbidity, mortality and central nervous system symptoms. In this study we examined the relationship of blood brain and intestinal barrier dysfunction in relation to uraemic environment and increased risk of developing neurologic complications and mortality. In addition, potential proteins conferring the junctional communications were assessed. Method The study included serum samples from 216 prevalent haemodialysis (HD), 80 peritoneal dialysis (PD) and 80 healthy subjects. Permeability of the BBB was evaluated by measuring serum concentrations for brain-specific biomarkers S100B, NSE (neuron specific enolase), BDNF (brain-derived neurotrophic factor), GFAP (glial fibrillary acidic protein) using ELISA. TMAO (trimethylamine-N-Oxide) as a surrogate of gut generated uraemic toxins was analysed by mass spectrophotometry. Subcutaneous fat tissues with identified microvessels from 10 kidney transplant recipients and 11 donors were examined for expression of tight junction proteins claudin-5, occludin and JAM-1 (junction adhesion molecule-1) by immunohistochemical staining. Results HD and PD groups showed elevated cholesterol, triglyceride, creatinine, hsCRP and lower BMI, and P-albumin compared to healthy controls. BDNF serum concentrations were lower in both HD (14.0 ng/mL, IQR 8.7-19.2) and PD (17.9 ng/mL, IQR 14.4-23.4) vs controls (20.2 ng/mL, IQR 16.7-25.7). Similarly, S100B serum concentrations were lower in both HD (31.6 pg/mL, IQR 9.4-186) and PD (49.4 pg/mL, IQR 9.8-118) vs control (87.3 pg/mL, IQR 13.3-749). Conversely, NSE serum concentrations were higher in both HD (5.3 ng/mL, IQR 4.4-6.6) and PD (4.0 ng/mL, IQR 3.6-4.7) vs controls (3.5 ng/mL, IQR 2.9-4.3). Finally, TMAO serum concentration were also higher in both HD (6.4 ng/μL, IQR 4.0-11.2) and PD (3.8 ng/μL, IQR 2.2-6.3) vs controls (0.4 ng/μL, IQR 0.3-0.6). No significant sex differences in biomarker concentration were found, except for TMAO in healthy controls. Immunohistochemistry studies of endothelial tight junction proteins in microvessels, within the subcutaneous fat tissues, showed reduced expression of claudin-5 (5%), occludin (6%) and JAM-1 (5%) in kidney transplant patients vs donors (7%, 8% and 8%, respectively), and ongoing studies are indicating a trend for altered expression of tight junction proteins after ex vivo stimulation with TMAO. Conclusion We report that CKD5 patients showed disruption of BBB and intestinal barrier resulting in altered circulating serum levels of brain-specific biomarkers, secondary to a disruption in the tight junction protein markers in microvasculature of adipose tissue. These findings imply that it is important to continuously monitor cognitive function(s) in CKD. Further studies are needed to assess direct effect of TMAO on tight junction proteins which confer vascular permeability.

Morphometric Study of Lateral Ventricles of Brain by MRI in Healthy Adults in Northern Zone of Bangladesh

Background & Objective: The present study was done to provide information about the morphometric measurement of lateral ventricles of human brain in relation to age and sex in northern Bangladeshi people.
 Methods: This cross-sectional study was conducted in the Department of Anatomy, Rajshahi Medical College, Rajshahi over a period one year from July 2014 to June 2015. All patients attending at Radiology & Imaging Department of Rajshahi Medical College Hospital and at different private hospitals and clinics of Rajshahi city and had normal MRI scan of brain were the study population. A total of 60 individuals of both sexes and age ranging between 18-50 years were included in the study. Having obtained ethical clearance from the Ethical Committee and verbal consent from the patients, the data collection was commenced. Patients were asked to lie on the MRI table in supine position with head fixed and coil placed around the head. MRI was done with MRI machine (Airis II Hitachi 0.3 Tesla) and images were taken by T1WI, T2WI, STAIR, FLAIR. Images were taken from axial, sagittal and coronal planes with sequence slice thickness being 7 mm. From the images of axial slices, six proper slices were selected.
 Result: Age distribution of the subjects with respect to sex shows that nearly two-thirds (63.3%) of the female subjects were 30 or younger than 30 years old, whereas 50% of the male subjects were early middle-aged (p = 0.110). The mean lengths of frontal horn of right and left lateral ventricles in male subjects were significantly greater than those in female subjects (p = 0.002 and p = 0.001 respectively). Likewise, the right and left ventricular bodies in male subjects were significantly longer than those of their female counterparts (p = 0.033 and p = 0.012 respectively). The length of frontal horn of the lateral ventricles was found to increase with age up to 40 years in both right and left ventricles and then it began to decrease. The mean lengths of frontal horn of right and left lateral ventricles at ages ≤ 30, 31-40 and > 40 years were 27.25, 28.74 and 26.0 mm and 27.57, 28.93 and 27.19 mm respectively. While the three measures of length of frontal horn of right lateral ventricles were significantly heterogeneous (p = 0.049), the three measures of length of frontal horn of left lateral ventricles were not significantly different (p = 0.141).The mean lengths of body of right and left lateral ventricles at different ages were 40.40, 43.98, 45.11 mm and 41.06, 44.52 and 45.21 mm respectively (p = 0.001 andp = 0.001 respectively).
 Conclusion: The present study concluded that the lateral ventricles vary in size within certain limit according to age, sex and laterality. All the parameters of lateral ventricles (lengths of frontal horn, length of ventricular body) were significantly larger in males than those in females. While the length of frontal horn of the lateral ventricles (of both sides) increases in size up to the age of 40 years and thereafter regresses, the length of ventricular body bears a linear relationship with age throughout life-span.
 Ibrahim Card Med J 2020; 10 (1&2): 45-50

Hypothalamic insulin signalling as a nexus regulating mood and metabolism.

Insulin has long been known as a metabolic hormone critical in the treatment of diabetes for its peripheral effects on blood glucose. However, in the last 50years, insulin has entered the realm of neuroendocrinology and many studies have described its function on insulin receptors in the brain in relation to both metabolic and mood disorders. Indeed, rodent models of impaired insulin signalling show signs of dysregulated energy and glucose homeostasis, as well as anxiety-like and depressive behaviours. Importantly, many metabolic diseases such as obesity and diabetes increase the risk of developing mood disorders; however, the brain mechanisms underlying the connection between metabolism and mood remain unresolved. We present the current literature on the importance of the insulin receptor with respect to regulating glucose and energy homeostasis and mood-related behaviours. Specifically, we hypothesise that the insulin receptor in the hypothalamus, classically known as the homeostatic centre of the brain, plays a causal role in linking metabolic and behavioural effects of insulin signalling. In this review, we discuss insulin signalling in the hypothalamus as a critical point of neural integration controlling metabolism and mood.

T Cells Actively Infiltrate the White Matter of the Aging Monkey Brain in Relation to Increased Microglial Reactivity and Cognitive Decline

Normal aging is characterized by declines in processing speed, learning, memory, and executive function even in the absence of neurodegenerative diseases such as Alzheimer's Disease (AD). In normal aging monkeys and humans, neuronal loss does not account for cognitive impairment. Instead, loss of white matter volume and an accumulation of myelin sheath pathology begins in middle age and is associated with cognitive decline. It is unknown what causes this myelin pathology, but it likely involves increased neuroinflammation in white matter and failures in oligodendrocyte function (maturation and repair). In frontal white matter tracts vulnerable to myelin damage, microglia become chronically reactive and secrete harmful pro-inflammatory cytokines. Despite being in a phagocytic state, these microglia are ineffective at phagocytosing accruing myelin debris, which directly inhibits myelin sheath repair. Here, we asked whether reported age-related increases in pro-inflammatory markers were accompanied by an adaptive immune response involving T cells. We quantified T cells with immunohistochemistry in the brains of 34 cognitively characterized monkeys and found an age-related increase in perivascular T cells that surround CNS vasculature. We found a surprising age-related increase in T cells that infiltrate the white matter parenchyma. In the cingulum bundle the percentage of these parenchymal T cells increased with age relative to those in the perivascular space. In contrast, infiltrating T cells were rarely found in surrounding gray matter regions. We assessed whether T cell infiltration correlated with fibrinogen extravasation from the vasculature as a measure of BBB leakiness and found no correlation, suggesting that T cell infiltration is not a result of passive extravasation. Importantly, the density of T cells in the cingulum bundle correlated with microglial reactivity and with cognitive impairment. This is the first demonstration that T cell infiltration of white matter is associated with cognitive decline in the normal aging monkey.

The role of interindividual licking received and dopamine genotype on later-life licking provisioning in female rat offspring.

IntroductionRat mothers exhibit natural variations in care that propagate between generations of female offspring. However, there is limited information on genetic variation that could influence this propagation.MethodsWe assessed early‐life maternal care received by individual female rat offspring, later‐life maternal care provisioning, and dopaminergic activity in the maternal brain in relation to naturally occurring genetic polymorphisms linked to the dopaminergic system. We also conducted a systematic analysis of other genetic variants potentially related to maternal behavior in our Long‐Evans rat population.ResultsWhile we did not find a direct relationship between early‐life licking received and later‐life licking provisioning, this relationship was indirectly affected by dopamine levels in the nucleus accumbens and dependent on variation in the dopamine receptor 2 gene (rs107017253). More specifically, female rat offspring with the A/G genotype showed a positive relationship between average licking received and dopamine levels in the nucleus accumbens of the maternal brain; there was no relationship with female rat offspring with the A/A genotype. The higher dopamine levels in the nucleus accumbens corresponded with higher maternal licking provisioning from postnatal days 2–9. We also discovered and validated several new variants that were predicted by our systematic analysis.ConclusionOur findings suggest that genetic variation influences the relationship between early‐life maternal care received and the dopaminergic system of the maternal brain, which can indirectly influence later‐life maternal care provisioning.

MODALITĂȚI DE GESTIONARE A TULBURĂRILOR DE COMPORTAMENT ALE ELEVILOR

The human mind is the subject of research for various fields of activity. Socio-human research fields investigate the brain's relationship with the mind, its circumstantial and relational functionality, the biological support and the complex processes of the soul, the principles of its formation and the relationship with consciousness, as well as its mode of action at the level of the human communities. Besides these perspectives, there is a special domain of mind research: that of Christian patristic spirituality. But what are the research objectives of Christian spirituality with regard to the human mind? And why did the uman mind come to the attention of the holy Fathers of the Church? From the texts of Christian anthropology and spirituality it follows that the mind has become a subject of research because the most intimate union between man and God is at its level. This study is centered on the analysis of St. Maximus the Confessor's observations about the human mind and its spiritual possibilities

What COVID-19 tells us about the self: The deep intersubjective and cultural layers of our brain.

The COVID-19 crisis is affecting our sense of self and touches upon our existential fears. This extends to the self-other relationship, as there is both being infected and infecting the other. What does this pandemic crisis tell us about our self and relatedness, its cultural differences, and how these are rooted in the brain's relation to the world? First, we discuss the psychological and neuronal features of self and self-other relation and how they are rooted in a deeper layer of the brain's neural activity complementing its cognitive surface layer. Second, we demonstrate cultural differences of Eastern and Western concepts of the self (i.e., independency and interdependency) and how these reflect the manifestation of the brain's neuro-social and neuro-ecological alignment. Finally, we highlight the intersubjective and cultural nature of the self and its surface in the COVID-19 crisis. Discussing various lines of empirical data showing the brain's intimate alignment to both social and ecological environmental contexts, our results support the assumption of the brain's deep layer features by laying bare a continuum of different degrees of neuro-social and neuro-ecological alignment. This entails a two-stage model of self with neuro-social-ecological and psychological levels that extends the previously suggested basis model of self-specificity. We conclude that the current pandemic shows the importance of the deeper intersubjective and cultural layers of both the self and brain; their neglect can be life-threatening for the self and others and, paradoxically, might reduce, rather than enlarge, the self's sense of freedom and independence.

A Systematic Approach to Dissection of the Equine Brain-Evaluation of a Species-Adapted Protocol for Beginners and Experts.

Introduction of new imaging modalities for the equine brain have refocused attention on the horse as a natural model for ethological, neuroanatomical, and neuroscientific investigations. As opposed to imaging studies, strategies for equine neurodissection still lack a structured approach, standardization and reproducibility. In contrast to other species, where adapted protocols for sampling have been published, no comparable guideline is currently available for equids. Hence, we developed a species-specific slice protocol for whole brain vs. hemispheric dissection and tested its applicability and practicability in the field, as well as its neuroanatomical accuracy and reproducibility. Dissection steps are concisely described and depicted by schematic illustrations, photographs and instructional videos. Care was taken to show the brain in relation to the raters' hands, cutting devices and bench surface. Guidance is based on a minimum of external anatomical landmarks followed by geometric instructions that led to procurement of 14 targeted slabs. The protocol was performed on 55 formalin-fixed brains by three groups of investigators with different neuroanatomical skills. Validation of brain dissection outcomes addressed the aptitude of slabs for neuroanatomical studies as opposed to simplified routine diagnostic purposes. Across all raters, as much as 95.2% of slabs were appropriate for neuroanatomical studies, and 100% of slabs qualified for a routine diagnostic setting. Neither autolysis nor subfixation significantly affected neuroanatomical accuracy score, while a significant negative effect was observed with brain extraction artifacts. Procedure times ranged from 14 to 66 min and reached a mean duration of 23.25 ± 7.93 min in the last of five trials in inexperienced raters vs. 16 ± 2.83 min in experts, while acceleration of the dissection did not negatively impact neuroanatomical accuracy. This protocol, derived analogously to the consensus report of the International Veterinary Epilepsy Task Force in dogs and cats, allows for systematic, quick and easy dissection of the equine brain, even for inexperienced investigators. Obtained slabs feature virtually all functional subcompartments at suitable planes for both diagnostic and neuroscientific investigations and complement the data obtained from imaging studies. The instructive protocol and brain dissection videos are available in Supplementary Material.

Is Focal Cortical Dysplasia/Epilepsy Caused by Somatic MTOR Mutations Always a Unilateral Disorder?

ObjectiveTo alert about the wide margin of unpredictability that distribution of somatic MTOR mosaicism may have in the brain and the risk for independent epileptogenesis arising from the seemingly healthy contralateral hemisphere after complete removal of epileptogenic focal cortical dysplasia (FCD).MethodsClinical, EEG, MRI, histopathology, and molecular genetics in 2 patients (1 and 2) treated with focal resections and subsequent complete hemispherectomy for epileptogenic FCD due to somatic MTOR mutations. Autoptic brain study of bilateral asymmetric hemispheric dysplasia and identification of alternative allele fraction (AAF) rates for AKT1 (patient 3).ResultsThe strongly hyperactivating p.Ser2215Phe (patient 1) and p.Leu1460Pro (patient 2) MTOR mutations were at low-level AAF in the dysplastic tissue. After repeated resections and eventual complete hemispherectomy, both patients manifested intractable seizures arising from the contralateral, seemingly healthy hemisphere. In patient 3, the p.Glu17Lys AKT1 mutation exhibited random distribution and AAF rates in different tissues with double levels in the more severely dysplastic cerebral hemisphere.ConclusionsOur understanding of the distribution of somatic mutations in the brain in relation to the type of malformation and its hypothesized time of origin may be faulty. Large studies may reveal that the risk of a first surgery being disappointing might be related more to the specific somatic mammalian target of rapamycin mutation identified than to completeness of resection and that the advantages of repeated resections after a first unsuccessful operation should be weighed against the risk of the contralateral hemisphere becoming in turn epileptogenic.

Brain Iron Content in Egyptian Patients with Sickle Cell Disease: Impact on Neurocognitive Functions

Background:Children with sickle cell disease (SCD) are at a high risk for neurocognitive impairment which may be due to iron overload in brain tissue or hemoglobin polymerization and endothelial dysfunction.Primary objectivewas measuring brain iron content (using R2* values) in the caudate and thalamic regions through quantitative brain MRI in Egyptian adolescents and young adults with multi-transfused SCD in comparison to beta thalassemia major (BTM) and age- and sex-matched healthy controls.Secondary objectiveswere evaluating the impact of brain iron content on neurocognitive functions of SCD patients and its association with MRI assessment of liver iron concentration (LIC) and cardiac iron (myocardial T2*).Methods: 32 children and young adults with SCD (mean age: 15.3 ± 3.7, 19 males and 13 females), 15 BTM (mean age: 19.4 ± 4.3, 7 males and 8 females) and 11 healthy control age- and gender-matched were recruited. Thorough clinical assessment, hematological and serum ferritin were performed. Brain MRI study using multi-echo fast gradient echo sequence was performed only for 15 patients with SCD, 15 patients with BTM and 11 controls and brain R2* values of both caudate and thalamic regions (right and left sides) were calculated. LIC and myocardial T2 were performed for; 15 with SCD and 15 with BTM. 32 SCD patients were examined for the neurocognitive functions; Wechsler IV Intelligence scale (verbal, perceptual, memory, processing and total IQ), Benton Visual Retention Test and Brief Psychiatric Rating Scale (BPRS).Results:For SCD patients their mean transfusion index was 174.70±63.98ml/kg/year and mean iron overload/day 0.30±0.12 mg/kg. 30 (93.8%) all SCD patients were on regular chelation therapy; 16 were on deferiprone and 16 were on combined chelation over last 5 years. Of those 32 SCD patients; 20 received concomitantly hydroxyurea therapy. Mean total IQ for SCD patients was 86.9±10.7; 68.9% had under- threshold <90 IQ and 27.5% had average (90-109) IQ. 12.5% of SCD patients had moderate to severe anxiety and 60.8% had of SCD patients had depression. No significant differences were found between SCD, BTM as regards LIC (p=0.102) No significant differences were found between SCD, BTM and control group in all regions of interests in brain MRI except that left thalamus R2* higher in BTM patients than both SCD and controls (p=0.032). R2* values of different regions of brain in relation with the studied parameters of SCD patients was not significant except that mean right caudate R2* was higher in female 17.4±0.8 than male 15.6±1.7 (p=0.044). The correlation coefficients showed no significant association between brain R2* and LIC or heart R2* values of SCD patients. There were positive correlation between left caudate R2* and both age and HbS%, negative correlation between transfusion index and right thalamus R2*, negative correlation between HbA% and left caudate R2* among SCD patients.Conclusion:Brain iron content in adolescents and young adults with SCD was not significantly different from either controls or BTM; SCD had high prevalence of neurocognitive dysfunction, which could not be explained by brain iron content or distribution. Figure 1 Disclosures No relevant conflicts of interest to declare.

Chronic Airway Allergy Induces Pro-Inflammatory Responses in the Brain of Wildtype Mice but Not 3xTgAD Mice

The effects of systemic inflammation on the pathogenesis of Alzheimer’s disease (AD) are not clarified, both beneficial and deleterious effects being reported. Allergy is accompanied by a systemic inflammatory response and some epidemiological studies have reported a positive association between a history of allergy/asthma and dementia. To investigate whether chronic airway allergy influences the inflammatory status in the brain, AD-like pathology, and behaviour in relation to AD, we induced chronic airway allergy in triple transgenic AD (3xTgAD) and wildtype (WT) mice by repeated exposure to ovalbumin (OVA) as allergen. Behavioural tests relevant for hippocampus-dependent behaviour were performed. We found that allergy significantly increased the brain levels of immunoglobulin (Ig) G, IgE. In 3xTgAD mice, allergy increased the levels of decay accelerating factor and decreased the phosphorylation of p38. In contrast, allergy increased the levels of interleukin (IL)-1β and complement component 1q (C1q) in WT mice. Bronchoalveolar lavage fluid analysis confirmed eosinophilia in both genotypes, but the basal levels of eosinophils were lower in 3xTgAD mice. In summary, allergy induced predominantly anti-inflammatory effects in 3xTgAD mice, and pro-inflammatory effects in WT mice, thus being another potential factor to be considered when studying AD pathogenesis.