Increase In Brain Volume Research Articles

Mechanisms underlying cognitive deficits in a mouse model for Costello Syndrome are distinct from other RASopathy mouse models

RASopathies, characterized by germline mutations in genes encoding proteins of the RAS-ERK signaling pathway, show overlapping phenotypes, which manifest themselves with a varying severity of intellectual disability. However, it is unclear to what extent they share the same downstream pathophysiology that underlies the cognitive deficits. Costello syndrome (CS) is a rare RASopathy caused by activating mutations in the HRAS gene. Here we investigated the mechanisms underlying the cognitive deficits of HRasG12V/G12V mice. HRasG12V/G12V mice showed robust upregulation of ERK signaling, neuronal hypertrophy, increased brain volume, spatial learning deficits, and impaired mGluR-dependent long-term depression (LTD). In contrast, long-term potentiation (LTP), which is affected in other RASopathy mouse models was unaffected. Treatment with lovastatin, a HMG-CoA-Reductase inhibitor which has been shown to rescue the behavioral phenotypes of mouse models of NF1 and Noonan syndrome, was unable to restore ERK signaling and the cognitive deficits of HRasG12V/G12V mice. Administration of a potent mitogen-activated protein kinase (MEK) inhibitor rescued the ERK upregulation and the mGluR-LTD deficit of HRasG12V/G12V mice, but failed to rescue the cognitive deficits. Taken together, this study indicates that the fundamental molecular and cellular mechanisms underlying the cognitive aspects of different RASopathies are remarkably distinct, and may require disease specific treatments.

The pro-cognitive mechanisms of physical exercise in people with schizophrenia.

Schizophrenia is associated with pervasive cognitive deficits which are unresponsive to antipsychotic medications. Physical exercise has been shown to improve cognitive functioning in people with schizophrenia, although the mechanisms for this are unclear. We conducted a systematic review of all exercise intervention studies which reported changes in brain structure, connectivity or peripheral biomarkers which could underlie cognitive improvements from exercise in schizophrenia. An electronic database search was conducted on 22 September 2016 using keywords relevant to exercise and neurocognition in schizophrenia. The search returned 2342 articles. Sixteen were eligible for inclusion, reporting data from 14 independent trials of 423 patients with schizophrenia. Seven studies used neuroimaging to examine the impact of exercise on brain structure and connectivity in schizophrenia, whereas seven other studies examined peripheral biomarkers to assess the effects of exercise. Imaging studies collectively indicated that exercise can increase brain volume in people with schizophrenia, although the regions which responded to exercise varied across studies. Most biomarker studies assessed the effects of exercise on serum levels of BDNF. Several studies found significant increases from exercise along with positive correlations between BDNF and cognitive enhancements (indicating a mechanistic link), although other studies did not observe this relationship. In conclusion, the cognitive benefits of exercise in schizophrenia may be due to exercise stimulating neurogenesis, perhaps by up-regulating BDNF, although current evidence is insufficient to draw definitive conclusions. Further exploration of the pro-cognitive mechanisms of exercise in schizophrenia would inform the development of optimal interventions for reducing cognitive impairments in this population. Linked Articles This article is part of a themed section on Pharmacology of Cognition: a Panacea for Neuropsychiatric Disease? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.19/issuetoc.

Early brain development in infants at high risk for autism spectrum disorder.

SummaryBrain enlargement has been observed in children with Autism Spectrum Disorder (ASD), but the timing of this phenomenon and its relationship to the appearance of behavioral symptoms is unknown. Retrospective head circumference and longitudinal brain volume studies of 2 year olds followed up at age 4 years, have provided evidence that increased brain volume may emerge early in development.1, 2 Studies of infants at high familial risk for autism can provide insight into the early development of autism and have found that characteristic social deficits in ASD emerge during the latter part of the first and in the second year of life3,4. These observations suggest that prospective brain imaging studies of infants at high familial risk for ASD might identify early post-natal changes in brain volume occurring before the emergence of an ASD diagnosis. In this prospective neuroimaging study of 106 infants at high familial risk of ASD and 42 low-risk infants, we show that cortical surface area hyper-expansion between 6-12 months of age precedes brain volume overgrowth observed between 12-24 months in the 15 high-risk infants diagnosed with autism at 24 months. Brain volume overgrowth was linked to the emergence and severity of autistic social deficits. A deep learning algorithm primarily using surface area information from brain MRI at 6 and 12 months of age predicted the diagnosis of autism in individual high-risk children at 24 months (with a positive predictive value of 81%, sensitivity of 88%). These findings demonstrate that early brain changes unfold during the period in which autistic behaviors are first emerging.

The assessment of fetal brain growth in diabetic pregnancy using in utero magnetic resonance imaging

To assess fetal brain growth over the third trimester in pregnant women with diabetes using in utero magnetic resonance imaging (iuMRI) to determine if greater brain growth occurs in type 1 (T1DM) when compared to gestational (GDM) diabetes mellitus. Each consented participant was scanned at three fixed times during the third trimester using iuMRI. One hundred and fifty-seven patients were approached, 48 participants were recruited, and 36 complete data sets were analysed. Three-dimensional (3D) iuMRI volume data sets were manually segmented using software to construct models of the fetal brain from which brain volumes could be calculated. Inter-rater analysis was performed, and volume differences and growth rates were compared between T1DM and GDM. Recruitment proved difficult with low uptake and high attrition rates (77.1%). Inter-rater analysis revealed excellent correlation (intraclass correlation coefficient=0.93, p<0.001) and agreement with no significant difference between operators (p=0.194). There was no evidence of increased brain volume in the T1DM group. Growth rates between visit 1 and 3 for T1DM and GDM were not significantly different (p=0.095). T1DM brain volumes were not significantly larger than GDM volumes and there was no significant divergence of brain growth over the third trimester. Constructing volume models from 3D iuMRI acquisitions is a novel technique that can be used to assess fetal brain growth. No specialist software or knowledge is required. Larger studies attempting to recruit pregnant women in the later stages of pregnancy should employ multicentre recruitment to overcome recruitment difficulties and high attrition rates.

Sexual Dimorphism in Craniometric Characteristics of Occipital Bone in Adult Human Skulls from West Bengal, India

ABSTRACTIn human evolution, changes in the anatomical features of skull were related to bipedalism and increase in brain volume. Three important landmarks on occipital bone are asterion (ast), inio...

Protection against Blast-Induced Traumatic Brain Injury by Increase in Brain Volume.

Blast-induced traumatic brain injury (bTBI) is a leading cause of injuries in recent military conflicts and it is responsible for an increased number of civilian casualties by terrorist attacks. bTBI includes a variety of neuropathological changes depending on the intensity of blast overpressure (BOP) such as brain edema, neuronal degeneration, diffuse axonal damage, and vascular dysfunction with neurological manifestations of psychological and cognitive abnormalities. Internal jugular vein (IJV) compression is known to reduce intracranial compliance by causing an increase in brain volume and was shown to reduce brain damage during closed impact-induced TBI. We investigated whether IJV compression can attenuate signs of TBI in rats after exposure to BOP. Animals were exposed to three 110 ± 5 kPa BOPs separated by 30 min intervals. Exposure to BOP resulted in a significant decrease of neuronal nuclei (NeuN) together with upregulation of aquaporin-4 (AQP-4), 3-nitrotyrosine (3-NT), and endothelin 1 receptor A (ETRA) expression in frontal cortex and hippocampus one day following exposures. IJV compression attenuated this BOP-induced increase in 3-NT in cortex and ameliorated the upregulation of AQP-4 in hippocampus. These results suggest that elevated intracranial pressure and intracerebral volume have neuroprotective potential in blast-induced TBI.

Influence of Positive End-Expiratory Pressure Ventilation on Cerebral Perfusion and Cardiac Hemodynamics

Objective: Positive end-expiratory pressure (PEEP) ventilation is used to prevent alveolar collapse and improve oxygenation. PEEP ventilation hinders venous backflow to the right atrium as well as venous outflow from the brain including the spinal cord. This may have an effect on cardiac output (CO) and could result in an elevation in intracranial pressure (ICP) — an important cause of secondary brain injury. The aim of this study was to investigate the effect of moderate changes in PEEP values on hemodynamics and cerebral perfusion in neurological patients experiencing respiratory failure. Methods: The study focused on 7 patients in a neurological intensive care unit who suffered from respiratory failure. Cerebral blood flow velocity was measured using transcranial color-coded duplex sonography (TCCS) while moderate changes in PEEP levels (10 cm, 7 cm or 5 cm H2O) were made to investigate cerebral arterial blood flow velocity, third ventricular diameter, and midline shift. Simultaneously, cardiac output was measured using a minimally invasive hemodynamic monitoring system (Vigileo® or PiCCO®). Results: Rising PEEPs resulted in a non-significant trend toward increased brain volume, as shown by a mild linear regression of changes in third ventricular diameter. However, no significant changes in cerebral blood flow parameters or hemodynamics values such as blood pressure, heart frequency or cardiac output, were noticed. Conclusion: Low to moderate changes in PEEP appear to increase brain volume slightly, but cerebral autoregulatory compensatory mechanisms are sufficient to stabilize cerebral perfusion pressure and intravasal volume status. The effects of these changes in PEEP may be challenging in patients with impaired cerebral autoregulation (for example, in patients after subarachnoid hemorrhage or severe brain trauma) as well as in patients requiring a high level of PEEP ventilation (that is, patients with acute respiratory distress syndrome). In such patients TCCS and cardiac hemodynamics monitoring are warranted.

The Pathophysiology of Brain Edema and Intracranial Hypertension

Brain edema is defined as an increase in brain volume resulting from abnormal accumulation of fluid within the brain parenchyma. Brain edema is a potentially life-threatening complication of neurocritical illness as it raises the intracranial pressure and may progress to brain herniation and death. The management of brain edema and increased intracranial pressure is a significant challenge in neurocritical care. The purpose of this review is to describe the pathophysiology of diverse types of brain edema. Key Words: Brain edema; Vasogenic edema; Cytotoxic edema; Interstitial edema; Intracranial hypertension

Increasing brain volume with physical exercise associated with lowering dementia risk

Increasing brain volume with physical exercise associated with lowering dementia risk

Brain structure in autism: a voxel-based morphometry analysis of the Autism Brain Imaging Database Exchange (ABIDE).

Increased brain volume is a consistent finding in young children with autism spectrum disorders (ASD); however, the regional specificity and developmental course of abnormal brain structure are less clear. Small sample sizes, particularly among voxel-based morphometry (VBM) investigations, likely contribute to this difficulty. Recently established large-scale neuroimaging data repositories have helped clarify the neuroanatomy of neuropsychiatric disorders such as schizophrenia and may prove useful in ASD. Structural brain images from the Autism Brain Imaging Database Exchange (ABIDE), which contains over 1100 participants, were analyzing using DARTEL VBM to investigate total brain and tissue volumes, and regional brain structure abnormalities in ASD. Two, overlapping cohorts were analyzed; an 'All Subjects' cohort (n = 833) that included all individuals with usable MRI data, and a 'Matched Samples' cohort (n = 600) comprised of ASD and TD individuals matched, within each site, on age and sex. Total brain and grey matter volumes were enlarged by approximately 1-2% in ASD; however, the effect reached statistical significance in only the All Subjects cohort. Within the All Subjects cohort, VBM analysis revealed enlargement of the left anterior superior temporal gyrus in ASD. No significant regional changes were detected in the Matched Samples cohort. There was a non-significant reduction in the correlation between IQ and TBV in ASD compared to TD. Brain structure abnormalities in ASD individuals age 6 and older consists of a subtle increase in total brain volume due to enlargement of grey matter with little evidence of regionally specific effects.

Anterior commissure versus corpus callosum: A quantitative comparison across mammals

Mammals rely on two major pathways to transfer information between the two hemispheres of the brain: the anterior commissure and the corpus callosum. Metatheria and monotremes rely exclusively on the anterior commissure for interhemispheric transfer between the isocortices and olfactory allocortices of each side, whereas Eutheria use a combination of the anterior commissure and an additional pathway exclusive to Eutheria, the corpus callosum. Midline cross-sectional area of the anterior commissure and corpus callosum were measured in a range of mammals from all three infraclasses and plotted against brain volume to determine how midline anterior commissure area and its size relative to the corpus callosum vary with brain size and taxon. In Metatheria, the square root of anterior commissure area rises in almost direct proportion with the cube root of brain volume (i.e. the ratio of the two is relatively constant), whereas among Eutheria the ratio of the square root of anterior commissure area to the cube root of brain volume declines slightly with increasing brain size. The total of isocortical and olfactory allocortical commissure area rises more rapidly with increasing brain volume among Eutheria than among Metatheria. This means that the midline isocortical and olfactory allocortical commissural area of metatherians with large brains (about 70ml) is only about 50% of that among eutherians with similarly sized brains. On the other hand, isocortical and olfactory allocortical commissural area is similar in Metatheria and Eutheria at brain volumes around 1ml. Among the Eutheria, some groups make less use of the anterior commissure pathway than do others: soricomorphs, rodents and cetaceans have smaller anterior commissures for their brain size than do afrosoricids, erinaceomorphs and proboscideans. The findings suggest that use of the anterior commissural route for isocortical commissural connections may have placed limitations on interhemispheric transfer of information among the metatherians, but only when brain size reaches 50ml or more.

A Prospective Pilot Investigation of Brain Volume, White Matter Hyperintensities, and Hemorrhagic Lesions after Mild Traumatic Brain Injury.

Traumatic brain injury (TBI) is among the most common neurological disorders. Hemorrhagic lesions and white matter hyperintensities (WMH) are radiological features associated with moderate and severe TBI. Brain volume reductions have also been observed during the months following injury. In concussion, no signs of injury are observed on conventional magnetic resonance imaging (MRI), which may be a true feature of concussion or merely due to the limited sensitivity of imaging techniques used so far. Moreover, it is not known whether volume reductions are due to the resolution of trauma-related edema or a true volume loss. Forty-five collegiate-level ice hockey players (20 females) and 15 controls (9 females), 40 players underwent 3-T MRI for hemorrhages [multi-echo susceptibility-weighted imaging (SWI)], WMH (three-dimensional fluid-attenuated inversion recovery), and brain volume at the beginning and the end of the hockey season. Concussed athletes underwent additional imaging and neuropsychological testing at 3 days, 2 weeks, and 2 months after injury. At the end of the hockey season, brain volume was reduced compared to controls by 0.32% (p < 0.034) in the whole cohort and by 0.26% (p < 0.09) in the concussed athletes. Two weeks and 2 months after concussion, brain volume was reduced by −0.08% (p = 0.027) and −0.23% (p = 0.035), respectively. In athletes, the WMH were significantly closer to the interface between gray matter and white matter compared to controls. No significant changes in the number of WMH over the duration of the study were found in athletes. No microhemorrhages were detected as a result of concussion or playing a season of ice hockey. We conclude that mild TBI does not lead to transient increases in brain volume and no new microbleeds or WMH are detectable after concussion. Brain volume reductions appear by 2 weeks after concussion and persist until at least 2 months after concussion. Brain volume is reduced between the beginning and the end of the ice hockey season.

Recent advances and future directions in preclinical research of arginine-vasopressin (AVP) receptor blocker conivaptan in the context of stroke.

Stroke is a major cause of mortality and permanent disability.The onset of stroke is followed by life-threatening pathophysiological responses including brain edema,elevation of intracranial pressure,disruption of blood-brain barrier(BBB),brain infarct and permanent tissue damage.Brain edema develops due to accumulation of water in intracellular and extracellular compartments of the brain,which causes an increase in brain volume and elevation of

Treatment of Nonsyndromic Craniosynostosis Using Multi-Split Osteotomy and Rigid Fixation with Absorbable Plates.

BackgroundNonsyndromic craniosynostosis is a relatively common craniofacial anomaly and various techniques were introduced to achieve its operative goals. Authors found that by using smaller bone fragments than that used in conventional cranioplasty, sufficiently rigid bone union and effective regeneration capacity could be achieved with better postoperative outcome, only if their stable fixation was ensured.MethodsThrough bicoronal incisional approach, involved synostotic cranial bone together with its surrounding areas were removed. The resected bone flap was split into as many pieces as possible. The extent of this ‘multi-split osteotomy’ depends on the degree of dysmorphology, expectative volume increment after surgery and probable dead space caused by bony gap between bone segments. Rigid interosseous fixation was performed with variable types of absorbable plate and screw. In all cases, the pre-operational three-dimensional computed tomography (3D CT) was checked and brain CT was taken immediately after the surgery. Also about 12 months after the operation, 3D CT was checked again to see postoperative morphology improvement, bone union, regeneration and intracranial volume change.ResultsThe bony gaps seen in the immediate postoperative brain CT were all improved as seen in the 3D CT after 12 months from the surgery. No small bone fragment resorption was observed. Brain volume increase was found to be made gradually, leaving no case of remaining epidural dead space.ConclusionWe conclude that it is meaningful in presenting a new possibility to be applied to not only nonsyndromic craniosynostosis but also other reconstructive cranial vault surgeries.

Progressive Loss of Brain Volume in Children with Sickle Cell Anemia: A Report from the Silent Cerebral Infarct Transfusion Trial Cohort

Introduction: Neurological injury is a common complication of sickle cell anemia (SCA). SCA is the most common cause of stroke in children between 1-14 years of age, while silent cerebral infarct is the most common neurologic injury in this population. Young children are particularly vulnerable to the adverse impact of strokes, and are at risk of cognitive and developmental deficits; thus, we sought to examine brain volume changes in children with SCA.The Silent Cerebral Infarct Transfusion (SIT) Trial was a multicenter trial designed to determine the efficacy of blood transfusion therapy for prevention of recurrent silent cerebral infarcts in participants with SCA. This intervention trial followed 196 children with SCA aged 5-14 years randomized to receive blood transfusion therapy or observation for 36 months (DeBaun et al. N Engl J Med. 2014;371(8):699-710). As a planned secondary analysis, we used the SIT Trial brain imaging archive to determine longitudinal brain volume change in children with SCA. We performed a multivariable analysis using demographic and clinical variables to identify predictors of brain volume change.MethodsSIT participants: The current study used a subset of the registered participants (n=169) in the SIT Trial with brain MRIs at study entry and exit, demographic and clinical information.Estimation of brain volume and percent brain volume change: Baseline brain volume and longitudinal percent brain volume change (PBVC) were derived from T1-weighted structural MRIs using the automated image analysis programs SIENAX and SIENA, respectively, from the FMRIB Software Library (FSL) (www.fmrib.ox.ac.uk/fsl). For each participant, PBVC was calculated between entry and exit brain MR scans, a mean time of 41 ± 6 months. A negative PBVC indicates a decrease in brain volume and a positive PBVC indicates an increase in brain volume. All analyses were performed blinded to the participant's identity.Statistical Analysis: A multivariable linear regression analysis was used to determine predictors of PBVC. The model included the following potential covariates : demographic variables (age, gender), laboratory measures (baseline oxygen saturation, steady state hemoglobin, steady state WBC, systolic blood pressure, % Hemoglobin F, steady state reticulocytes), clinical measures (acute chest syndrome and painful crisis rates), and regular transfusions provided as part of the trial.Results: Of the 169 SIT participants, 96 were male and 73 were female, including 80 participants in the observation group and 89 in the transfusion group. Median normalized brain volume was 1,237.6 cm3 at the study entry and 1,194.7 cm3 at exit. Baseline brain volume in males was different from females (1,290.6 cm3 vs. 1,166.6 cm3; p<0.001). Comparing total brain volumes from entry to exit, the mean percent brain volume change was -2.7% (median, -2.4%; SD, 2.75). Percent brain volume change in males was not different from females (-2.6% vs. -2.8%; p=0.75). In the multivariable analysis of demographic, clinical, and pain measures, age was the only significant predictor of PBVC (p<0.001) (Figure 1).Conclusion: Using longitudinal MRI images from the SIT Trial, we demonstrate progressive brain volume loss in children, with SCA with a mean percent brain volume change of -2.7% in the SIT Trial cohort. In comparison, brain volumes of children without SCA have been reported to remain stable in this age group (Cereb Cortex. 2012; 22 (1):1-12). We conclude that loss of brain volume begins early in children with SCA. Further investigations into the etiology of brain volume loss in children with SCA, and measures to better understand and reduce or prevent brain volume loss in SCA are needed.

Lipid metabolites of the phospholipase A2 pathway and inflammatory cytokines are associated with brain volume in paediatric cerebral malaria.

BackgroundCerebral malaria (CM) remains a significant cause of morbidity and mortality in children in sub-Saharan Africa. CM mortality has been associated with increased brain volume, seen on neuroimaging studies.MethodsTo examine the potential role of blood metabolites and inflammatory mediators in increased brain volume in Malawian children with CM, an association study was performed between plasma metabolites, cytokine levels and phospholipase A2 (PLA2) activity with brain volume.ResultsThe metabolomics analysis demonstrated arachidonic acid and other lysophospholipids to be positively associated with brain swelling. These lipids are products of the PLA2 enzyme and an association of plasma PLA2 enzymatic activity with brain swelling was confirmed. TNFα, which can upregulate PLA2 activity, was associated with brain volume. In addition, CCL2 and IL-8 were also associated with brain volume. Some of these cytokines can alter endothelial cell tight junction proteins and increase blood brain barrier permeability.ConclusionsTaken together, paediatric CM brain volume was associated with products of the PLA2 pathway and inflammatory cytokines. Their role in causality is unknown. These molecules will need to undergo testing in vitro and in animal models to understand their role in processes of increased brain volume. These observations provide novel data on host physiology associated with paediatric CM brain swelling, and may both inform pathogenesis models and suggest adjunct therapies that could improve the morbidity and mortality associated with paediatric CM.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-1036-1) contains supplementary material, which is available to authorized users.

Effects of long-term treatment on brain volume in patients with obstructive sleep apnea syndrome.

We assessed structural brain damage in obstructive sleep apnea syndrome (OSA) patients (21 males) and the effects of long-term continuous positive airway pressure (CPAP) treatment (18.2 ± 12.4 months; 8-44 months) on brain structures and investigated the relationship between severity of OSA and effects of treatment. Using deformation-based morphometry to measure local volume changes, we identified widespread neocortical and cerebellar atrophy in untreated patients compared to controls (59 males; Cohen's D = 0.6; FDR < 0.05). Analysis of longitudinally scanned magnetic resonance imaging (MRI) scans both before and after treatment showed increased brain volume following treatment (FDR < 0.05). Volume increase was correlated with longer treatment in the cortical areas that largely overlapped with the initial atrophy. The areas overlying the hippocampal dentate gyrus and the cerebellar dentate nucleus displayed a volume increase after treatment. Patients with very severe OSA (AHI > 64) presented with prefrontal atrophy and displayed an additional volume increase in this area following treatment. Higher impairment of working memory in patients prior to treatment correlated with prefrontal volume increase after treatment. The large overlap between the initial brain damage and the extent of recovery after treatment suggests partial recovery of nonpermanent structural damage. Volume increases in the dentate gyrus and the dentate nucleus possibly likely indicate compensatory neurogenesis in response to diminishing oxidative stress. Such changes in other brain structures may explain gliosis, dendritic volume increase, or inflammation. This study provides neuroimaging evidence that revealed the positive effects of long-term CPAP treatment in patients with OSA.

The bidirectional association between reduced cerebral blood flow and brain atrophy in the general population.

The question remains whether reduced cerebral blood flow (CBF) leads to brain atrophy or vice versa. We studied the longitudinal relation between CBF and brain volume in a community-dwelling population. In the Rotterdam Study, 3011 participants (mean age 59.6 years (s.d. 8.0)) underwent repeat brain magnetic resonance imaging to quantify brain volume and CBF at two time points. Adjusted linear regression models were used to investigate the bidirectional relation between CBF and brain volume. We found that smaller brain volume at baseline was associated with a steeper decrease in CBF in the whole population (standardized change per s.d. increase of total brain volume (TBV)=0.296 (95% confidence interval (CI) 0.200; 0.393)). Only in persons aged ⩾65 years, a lower CBF at baseline was associated with steeper decline of TBV (standardized change per s.d. increase of CBF=0.003 (95% CI -0.004; 0.010) in the whole population and 0.020 (95% CI 0.004; 0.036) in those aged ⩾65 years of age). Our results indicate that brain atrophy causes CBF to decrease over time, rather than vice versa. Only in persons aged >65 years of age did we find lower CBF to also relate to brain atrophy.

Corpus callosum area and brain volume in autism spectrum disorder: quantitative analysis of structural MRI from the ABIDE database.

Reduced corpus callosum area and increased brain volume are two commonly reported findings in autism spectrum disorder (ASD). We investigated these two correlates in ASD and healthy controls using T1-weighted MRI scans from the Autism Brain Imaging Data Exchange (ABIDE). Automated methods were used to segment the corpus callosum and intracranial region. No difference in the corpus callosum area was found between ASD participants and healthy controls (ASD 598.53±109mm(2); control 596.82±102mm(2); p=0.76). The ASD participants had increased intracranial volume (ASD 1,508,596±170,505mm(3); control 1,482,732±150,873.5mm(3); p=0.042). No evidence was found for overall ASD differences in the corpus callosum subregions.

Regulatory T cells ameliorate intrauterine growth retardation in a transgenic rat model for preeclampsia.

Preeclampsia is a multisystemic syndrome during pregnancy that is often associated with intrauterine growth retardation. Immunologic dysregulation, involving T cells, is implicated in the pathogenesis. The aim of this study was to evaluate the effect of upregulating regulatory T cells in an established transgenic rat model for preeclampsia. Application of superagonistic monoclonal antibody for CD28 has been shown to effectively upregulate regulatory T cells. In the first protocol (treatment protocol), we applied 1 mg of CD28 superagonist or control antibody on days 11 and 15 of pregnancy. In the second protocol (prevention protocol), the superagonist or control antibody was applied on days 1, 5, and 9. Superagonist increased regulatory T cells in circulation and placenta from 8.49±2.09% of CD4-positive T cells to 23.50±3.05% and from 3.85±1.45% to 23.27±7.64%, respectively. Blood pressure and albuminuria (30.6±15.1 versus 14.6±5.5 mg/d) were similar in the superagonist or control antibody-treated preeclamptic group for both protocols. Rats treated with CD28 superagonist showed increased pup weights in the prevention protocol (2.66±0.03 versus 2.37±0.05 g) and in the treatment protocol (3.04±0.04 versus 2.54±0.1 g). Intrauterine growth retardation, calculated by brain:liver weight ratio, was also decreased by the superagonist in both protocols. Further analysis of brain development revealed a 20% increase in brain volume by the superagonist. Induction of regulatory T cells in the circulation and the uteroplacental unit in an established preeclamptic rat model had no influence on maternal hypertension and proteinuria. However, it substantially improved fetal outcome by ameliorating intrauterine growth retardation.