brain Mediterranean Diet Helps Protect Aging Brain By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Mediterranean Diet Helps Protect Aging BrainCategory: Health NewsCreated: 4/27/2010 8:10:00 AMLast Editorial Review: 4/27/2010 12:00:00 AM Full Article
brain For a Healthy Aging Brain, 'Use It or Lose It' By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: For a Healthy Aging Brain, 'Use It or Lose It'Category: Health NewsCreated: 4/28/2012 11:00:00 AMLast Editorial Review: 4/30/2012 12:00:00 AM Full Article
brain Prenatal Pesticide Exposure May Harm Kids' Brains By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Prenatal Pesticide Exposure May Harm Kids' BrainsCategory: Health NewsCreated: 5/1/2012 11:01:00 AMLast Editorial Review: 5/1/2012 12:00:00 AM Full Article
brain Exercise Plus Computer Time May Boost Seniors' Brains By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Exercise Plus Computer Time May Boost Seniors' BrainsCategory: Health NewsCreated: 5/1/2012 6:05:00 PMLast Editorial Review: 5/2/2012 12:00:00 AM Full Article
brain In Some Brain Bleeds, Patients Do Better at High-Volume Hospitals By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: In Some Brain Bleeds, Patients Do Better at High-Volume HospitalsCategory: Health NewsCreated: 5/3/2012 6:05:00 PMLast Editorial Review: 5/4/2012 12:00:00 AM Full Article
brain New Clues to the Evolution of the Human Brain By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: New Clues to the Evolution of the Human BrainCategory: Health NewsCreated: 5/3/2012 6:05:00 PMLast Editorial Review: 5/4/2012 12:00:00 AM Full Article
brain Magnetic Brain Stimulation May Temporarily Dull Nicotine Craving By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Magnetic Brain Stimulation May Temporarily Dull Nicotine CravingCategory: Health NewsCreated: 4/26/2013 12:36:00 PMLast Editorial Review: 4/29/2013 12:00:00 AM Full Article
brain Sex Lives Often an Overlooked Casualty of Traumatic Brain Injury By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Sex Lives Often an Overlooked Casualty of Traumatic Brain InjuryCategory: Health NewsCreated: 4/29/2013 2:35:00 PMLast Editorial Review: 4/30/2013 12:00:00 AM Full Article
brain Brain Differences Seen in Kids With Conduct Problems By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Brain Differences Seen in Kids With Conduct ProblemsCategory: Health NewsCreated: 5/2/2013 12:35:00 PMLast Editorial Review: 5/3/2013 12:00:00 AM Full Article
brain Laughter May Work Like Meditation in the Brain By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Laughter May Work Like Meditation in the BrainCategory: Health NewsCreated: 4/27/2014 12:35:00 PMLast Editorial Review: 4/28/2014 12:00:00 AM Full Article
brain Type 2 Diabetes May Shrink the Brain, Study Suggests By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Type 2 Diabetes May Shrink the Brain, Study SuggestsCategory: Health NewsCreated: 4/29/2014 9:35:00 AMLast Editorial Review: 4/29/2014 12:00:00 AM Full Article
brain Japan Quake Shows How Stress Alters the Brain By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Japan Quake Shows How Stress Alters the BrainCategory: Health NewsCreated: 4/29/2014 12:35:00 PMLast Editorial Review: 4/30/2014 12:00:00 AM Full Article
brain Traumatic Brain Injury Common Among Homeless Men By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Traumatic Brain Injury Common Among Homeless MenCategory: Health NewsCreated: 4/30/2014 12:35:00 PMLast Editorial Review: 5/1/2014 12:00:00 AM Full Article
brain Brain Scans Spot Possible Clues to Chronic Fatigue Syndrome By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Brain Scans Spot Possible Clues to Chronic Fatigue SyndromeCategory: Health NewsCreated: 5/2/2014 12:35:00 PMLast Editorial Review: 5/2/2014 12:00:00 AM Full Article
brain Young Brains May Gain Skills When Parents Read to Kids By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Young Brains May Gain Skills When Parents Read to KidsCategory: Health NewsCreated: 4/25/2015 12:00:00 AMLast Editorial Review: 4/27/2015 12:00:00 AM Full Article
brain Scientists Pinpoint Brain's 'Hunger Circuit' in Mice By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Scientists Pinpoint Brain's 'Hunger Circuit' in MiceCategory: Health NewsCreated: 4/28/2015 12:00:00 AMLast Editorial Review: 4/28/2015 12:00:00 AM Full Article
brain Women's Brains May Have Tougher Time Recovering From Concussion By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Women's Brains May Have Tougher Time Recovering From ConcussionCategory: Health NewsCreated: 4/28/2015 12:00:00 AMLast Editorial Review: 4/28/2015 12:00:00 AM Full Article
brain Sleep Doesn't Come Easy to Those With Brain Injuries By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Sleep Doesn't Come Easy to Those With Brain InjuriesCategory: Health NewsCreated: 4/27/2016 12:00:00 AMLast Editorial Review: 4/28/2016 12:00:00 AM Full Article
brain Psychiatric Scars of Wartime Brain Injury May Linger for Years By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Psychiatric Scars of Wartime Brain Injury May Linger for YearsCategory: Health NewsCreated: 5/1/2017 12:00:00 AMLast Editorial Review: 5/2/2017 12:00:00 AM Full Article
brain Brain Research Fuels New Migraine Treatments By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Brain Research Fuels New Migraine TreatmentsCategory: Health NewsCreated: 5/3/2017 12:00:00 AMLast Editorial Review: 5/3/2017 12:00:00 AM Full Article
brain Nearby Lightning Shut Down a Woman's Brain Implant By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Nearby Lightning Shut Down a Woman's Brain ImplantCategory: Health NewsCreated: 5/1/2018 12:00:00 AMLast Editorial Review: 5/1/2018 12:00:00 AM Full Article
brain Breast Milk Has Biggest Benefit for Preemies' Brains: Study By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Breast Milk Has Biggest Benefit for Preemies' Brains: StudyCategory: Health NewsCreated: 4/27/2019 12:00:00 AMLast Editorial Review: 4/29/2019 12:00:00 AM Full Article
brain Morning Exercise Kick-Starts Seniors' Brains By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Morning Exercise Kick-Starts Seniors' BrainsCategory: Health NewsCreated: 5/2/2019 12:00:00 AMLast Editorial Review: 5/2/2019 12:00:00 AM Full Article
brain Could Alzheimer's Spread Like an Infection Throughout the Brain? By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Could Alzheimer's Spread Like an Infection Throughout the Brain?Category: Health NewsCreated: 5/1/2019 12:00:00 AMLast Editorial Review: 5/2/2019 12:00:00 AM Full Article
brain Key Areas of the Brain Triggered in Recent Heart Attack Survivors By www.medicinenet.com Published On :: Wed, 6 May 2020 00:00:00 PDT Title: Key Areas of the Brain Triggered in Recent Heart Attack SurvivorsCategory: Health NewsCreated: 5/5/2020 12:00:00 AMLast Editorial Review: 5/6/2020 12:00:00 AM Full Article
brain What Day Is It? This Is Your Brain on Quarantine By www.webmd.com Published On :: Thu, 07 May 2020 17:06:59 EST If it feels like all your internal clocks are melting as your stay-at-home days drone on, you are not alone. Researchers say that people in various levels of COVID-19 quarantine around the world are reporting a distorted sense of time. Full Article
brain Study Ties Brain Inflammation to Several Types of Dementia By www.medicinenet.com Published On :: Wed, 18 Mar 2020 00:00:00 PDT Title: Study Ties Brain Inflammation to Several Types of DementiaCategory: Health NewsCreated: 3/18/2020 12:00:00 AMLast Editorial Review: 3/18/2020 12:00:00 AM Full Article
brain Brain Plaques Signal Alzheimer's Even Before Other Symptoms Emerge: Study By www.medicinenet.com Published On :: Tue, 14 Apr 2020 00:00:00 PDT Title: Brain Plaques Signal Alzheimer's Even Before Other Symptoms Emerge: StudyCategory: Health NewsCreated: 4/13/2020 12:00:00 AMLast Editorial Review: 4/14/2020 12:00:00 AM Full Article
brain Potato & Sausages, Cold Cuts a Bad Combo for Your Brain By www.medicinenet.com Published On :: Thu, 23 Apr 2020 00:00:00 PDT Title: Potato & Sausages, Cold Cuts a Bad Combo for Your BrainCategory: Health NewsCreated: 4/22/2020 12:00:00 AMLast Editorial Review: 4/23/2020 12:00:00 AM Full Article
brain Blood Pressure Spikes at Night May Spell Trouble for Brain By www.medicinenet.com Published On :: Mon, 20 Apr 2020 00:00:00 PDT Title: Blood Pressure Spikes at Night May Spell Trouble for BrainCategory: Health NewsCreated: 4/17/2020 12:00:00 AMLast Editorial Review: 4/20/2020 12:00:00 AM Full Article
brain Long Periods in Space Alter Astronauts' Brains By www.medicinenet.com Published On :: Wed, 15 Apr 2020 00:00:00 PDT Title: Long Periods in Space Alter Astronauts' BrainsCategory: Health NewsCreated: 4/14/2020 12:00:00 AMLast Editorial Review: 4/15/2020 12:00:00 AM Full Article
brain Greenhouse Gases Bad for Your Brain By www.medicinenet.com Published On :: Fri, 24 Apr 2020 00:00:00 PDT Title: Greenhouse Gases Bad for Your BrainCategory: Health NewsCreated: 4/23/2020 12:00:00 AMLast Editorial Review: 4/24/2020 12:00:00 AM Full Article
brain Some NFL Players May Be Misdiagnosed With Brain Disease: Study By www.medicinenet.com Published On :: Tue, 28 Apr 2020 00:00:00 PDT Title: Some NFL Players May Be Misdiagnosed With Brain Disease: StudyCategory: Health NewsCreated: 4/27/2020 12:00:00 AMLast Editorial Review: 4/28/2020 12:00:00 AM Full Article
brain Magnetic Brain 'Zap' Shows Promise Against Severe Depression By www.medicinenet.com Published On :: Wed, 8 Apr 2020 00:00:00 PDT Title: Magnetic Brain 'Zap' Shows Promise Against Severe DepressionCategory: Health NewsCreated: 4/7/2020 12:00:00 AMLast Editorial Review: 4/8/2020 12:00:00 AM Full Article
brain Could AI Help Doctors Map Out Treatments for Brain Cancers? By www.medicinenet.com Published On :: Mon, 27 Apr 2020 00:00:00 PDT Title: Could AI Help Doctors Map Out Treatments for Brain Cancers?Category: Health NewsCreated: 4/24/2020 12:00:00 AMLast Editorial Review: 4/27/2020 12:00:00 AM Full Article
brain First Good Evidence That Brain Hits 'Replay' While You Sleep By www.medicinenet.com Published On :: Wed, 6 May 2020 00:00:00 PDT Title: First Good Evidence That Brain Hits 'Replay' While You SleepCategory: Health NewsCreated: 5/5/2020 12:00:00 AMLast Editorial Review: 5/6/2020 12:00:00 AM Full Article
brain In utero MRI identifies consequences of early-gestation alcohol drinking on fetal brain development in rhesus macaques [Neuroscience] By www.pnas.org Published On :: 2020-05-05T10:31:24-07:00 One factor that contributes to the high prevalence of fetal alcohol spectrum disorder (FASD) is binge-like consumption of alcohol before pregnancy awareness. It is known that treatments are more effective with early recognition of FASD. Recent advances in retrospective motion correction for the reconstruction of three-dimensional (3D) fetal brain MRI... Full Article
brain Closing the gap between mind and brain with the dynamic connectome [Neuroscience] By www.pnas.org Published On :: 2020-05-05T10:31:24-07:00 At the pinnacle of the 17th century scientific revolution, René Descartes, the father of modern philosophy, published his monumental Meditations on First Philosophy (1), in which he proposed a division between soul and body—mind and brain—with the former in charge of our thoughts and conscious decisions (res cogitans) and the... Full Article
brain The brains of six African mole-rat species show divergent responses to hypoxia [RESEARCH ARTICLE] By jeb.biologists.org Published On :: 2020-02-10T02:27:54-08:00 Samantha M. Logan, Kama E. Szereszewski, Nigel C. Bennett, Daniel W. Hart, Barry van Jaarsveld, Matthew E. Pamenter, and Kenneth B. StoreyMole-rats are champions of self-preservation, with increased longevity compared to other rodents their size, strong antioxidant capabilities, and specialized defenses against endogenous oxidative stress. However, how the brains of these subterranean mammals handle acute in vivo hypoxia is poorly understood. This study is the first to examine the molecular response to low oxygen in six different species of hypoxia-tolerant mole-rats from sub-Saharan Africa. Protein carbonylation, a known marker of DNA damage (hydroxy-2’-deoxyguanosine), and antioxidant capacity did not change following hypoxia but HIF-1 protein levels increased significantly in the brains of two species. Nearly 30 miRNAs known to play roles in hypoxia-tolerance were differentially regulated in a species-specific manner. The miRNAs exhibiting the strongest response to low oxygen stress inhibit apoptosis and regulate neuroinflammation, likely providing neuroprotection. A principal component analysis using a subset of the molecular targets assessed herein revealed differences between control and hypoxic groups for two solitary species (Georychus capensis and Bathyergus suillus), which are ecologically adapted to a normoxic environment, suggesting a heightened sensitivity to hypoxia relative to species that may experience hypoxia more regularly in nature. By contrast, all molecular data were included in the PCA to detect a difference between control and hypoxic populations of eusocial Heterocephalus glaber, indicating they may require many lower-fold changes in signaling pathways to adapt to low oxygen settings. Finally, none of the Cryptomys hottentotus subspecies showed a statistical difference between control and hypoxic groups, presumably due to hypoxia-tolerance derived from environmental pressures associated with a subterranean and social lifestyle. Full Article
brain Interaction of the Brain-Selective Sulfotransferase SULT4A1 with Other Cytosolic Sulfotransferases: Effects on Protein Expression and Function [Articles] By dmd.aspetjournals.org Published On :: 2020-04-09T08:02:00-07:00 Sulfotransferase (SULT) 4A1 is a brain-selective sulfotransferase-like protein that has recently been shown to be essential for normal neuronal development in mice. In the present study, SULT4A1 was found to colocalize with SULT1A1/3 in human brain neurons. Using immunoprecipitation, SULT4A1 was shown to interact with both SULT1A1 and SULT1A3 when expressed in human cells. Mutation of the conserved dimerization motif located in the C terminus of the sulfotransferases prevented this interaction. Both ectopically expressed and endogenous SULT4A1 decreased SULT1A1/3 protein levels in neuronal cells, and this was also prevented by mutation of the dimerization motif. During differentiation of neuronal SH-SY5Y cells, there was a loss in SULT1A1/3 protein but an increase in SULT4A1 protein. This resulted in an increase in the toxicity of dopamine, a substrate for SULT1A3. Inhibition of SULT4A1 using small interference RNA abrogated the loss in SULT1A1/3 and reversed dopamine toxicity. These results show a reciprocal relationship between SULT4A1 and the other sulfotransferases, suggesting that it may act as a chaperone to control the expression of SULT1A1/3 in neuronal cells. SIGNIFICANCE STATEMENT The catalytically inactive sulfotransferase (SULT) 4A1 may regulate the function of other SULTs by interacting with them via a conserved dimerization motif. In neuron-like cells, SULT4A1 is able to modulate dopamine toxicity by interacting with SULT1A3, potentially decreasing the metabolism of dopamine. Full Article
brain {alpha}-Synuclein filaments from transgenic mouse and human synucleinopathy-containing brains are maȷor seed-competent species [Molecular Bases of Disease] By www.jbc.org Published On :: 2020-05-08T03:41:14-07:00 Assembled α-synuclein in nerve cells and glial cells is the defining pathological feature of neurodegenerative diseases called synucleinopathies. Seeds of α-synuclein can induce the assembly of monomeric protein. Here, we used sucrose gradient centrifugation and transiently transfected HEK 293T cells to identify the species of α-synuclein from the brains of homozygous, symptomatic mice transgenic for human mutant A53T α-synuclein (line M83) that seed aggregation. The most potent fractions contained Sarkosyl-insoluble assemblies enriched in filaments. We also analyzed six cases of idiopathic Parkinson's disease (PD), one case of familial PD, and six cases of multiple system atrophy (MSA) for their ability to induce α-synuclein aggregation. The MSA samples were more potent than those of idiopathic PD in seeding aggregation. We found that following sucrose gradient centrifugation, the most seed-competent fractions from PD and MSA brains are those that contain Sarkosyl-insoluble α-synuclein. The fractions differed between PD and MSA, consistent with the presence of distinct conformers of assembled α-synuclein in these different samples. We conclude that α-synuclein filaments are the main driving force for amplification and propagation of pathology in synucleinopathies. Full Article
brain Brain manganese and the balance between essential roles and neurotoxicity [Molecular Bases of Disease] By www.jbc.org Published On :: 2020-05-08T03:41:14-07:00 Manganese (Mn) is an essential micronutrient required for the normal development of many organs, including the brain. Although its roles as a cofactor in several enzymes and in maintaining optimal physiology are well-known, the overall biological functions of Mn are rather poorly understood. Alterations in body Mn status are associated with altered neuronal physiology and cognition in humans, and either overexposure or (more rarely) insufficiency can cause neurological dysfunction. The resultant balancing act can be viewed as a hormetic U-shaped relationship for biological Mn status and optimal brain health, with changes in the brain leading to physiological effects throughout the body and vice versa. This review discusses Mn homeostasis, biomarkers, molecular mechanisms of cellular transport, and neuropathological changes associated with disruptions of Mn homeostasis, especially in its excess, and identifies gaps in our understanding of the molecular and biochemical mechanisms underlying Mn homeostasis and neurotoxicity. Full Article
brain 18F-FAC PET Visualizes Brain-Infiltrating Leukocytes in a Mouse Model of Multiple Sclerosis By jnm.snmjournals.org Published On :: 2020-05-01T06:31:37-07:00 Brain-infiltrating leukocytes contribute to multiple sclerosis (MS) and autoimmune encephalomyelitis and likely play a role in traumatic brain injury, seizure, and stroke. Brain-infiltrating leukocytes are also primary targets for MS disease-modifying therapies. However, no method exists for noninvasively visualizing these cells in a living organism. 1-(2'-deoxy-2'-18F-fluoroarabinofuranosyl) cytosine (18F-FAC) is a PET radiotracer that measures deoxyribonucleoside salvage and accumulates preferentially in immune cells. We hypothesized that 18F-FAC PET could noninvasively image brain-infiltrating leukocytes. Methods: Healthy mice were imaged with 18F-FAC PET to quantify if this radiotracer crosses the blood–brain barrier (BBB). Experimental autoimmune encephalomyelitis (EAE) is a mouse disease model with brain-infiltrating leukocytes. To determine whether 18F-FAC accumulates in brain-infiltrating leukocytes, EAE mice were analyzed with 18F-FAC PET, digital autoradiography, and immunohistochemistry, and deoxyribonucleoside salvage activity in brain-infiltrating leukocytes was analyzed ex vivo. Fingolimod-treated EAE mice were imaged with 18F-FAC PET to assess if this approach can monitor the effect of an immunomodulatory drug on brain-infiltrating leukocytes. PET scans of individuals injected with 2-chloro-2'-deoxy-2'-18F-fluoro-9-β-d-arabinofuranosyl-adenine (18F-CFA), a PET radiotracer that measures deoxyribonucleoside salvage in humans, were analyzed to evaluate whether 18F-CFA crosses the human BBB. Results: 18F-FAC accumulates in the healthy mouse brain at levels similar to 18F-FAC in the blood (2.54 ± 0.2 and 3.04 ± 0.3 percentage injected dose per gram, respectively) indicating that 18F-FAC crosses the BBB. EAE mice accumulate 18F-FAC in the brain at 180% of the levels of control mice. Brain 18F-FAC accumulation localizes to periventricular regions with significant leukocyte infiltration, and deoxyribonucleoside salvage activity is present at similar levels in brain-infiltrating T and innate immune cells. These data suggest that 18F-FAC accumulates in brain-infiltrating leukocytes in this model. Fingolimod-treated EAE mice accumulate 18F-FAC in the brain at 37% lower levels than control-treated EAE mice, demonstrating that 18F-FAC PET can monitor therapeutic interventions in this mouse model. 18F-CFA accumulates in the human brain at 15% of blood levels (0.08 ± 0.01 and 0.54 ± 0.07 SUV, respectively), indicating that 18F-CFA does not cross the BBB in humans. Conclusion: 18F-FAC PET can visualize brain-infiltrating leukocytes in a mouse MS model and can monitor the response of these cells to an immunomodulatory drug. Translating this strategy into humans will require exploring additional radiotracers. Full Article
brain Surfactant Expression Defines an Inflamed Subtype of Lung Adenocarcinoma Brain Metastases that Correlates with Prolonged Survival By clincancerres.aacrjournals.org Published On :: 2020-05-01T00:05:36-07:00 Purpose: To provide a better understanding of the interplay between the immune system and brain metastases to advance therapeutic options for this life-threatening disease. Experimental Design: Tumor-infiltrating lymphocytes (TIL) were quantified by semiautomated whole-slide analysis in brain metastases from 81 lung adenocarcinomas. Multi-color staining enabled phenotyping of TILs (CD3, CD8, and FOXP3) on a single-cell resolution. Molecular determinants of the extent of TILs in brain metastases were analyzed by transcriptomics in a subset of 63 patients. Findings in lung adenocarcinoma brain metastases were related to published multi-omic primary lung adenocarcinoma The Cancer Genome Atlas data (n = 230) and single-cell RNA-sequencing (scRNA-seq) data (n = 52,698). Results: TIL numbers within tumor islands was an independent prognostic marker in patients with lung adenocarcinoma brain metastases. Comparative transcriptomics revealed that expression of three surfactant metabolism-related genes (SFTPA1, SFTPB, and NAPSA) was closely associated with TIL numbers. Their expression was not only prognostic in brain metastasis but also in primary lung adenocarcinoma. Correlation with scRNA-seq data revealed that brain metastases with high expression of surfactant genes might originate from tumor cells resembling alveolar type 2 cells. Methylome-based estimation of immune cell fractions in primary lung adenocarcinoma confirmed a positive association between lymphocyte infiltration and surfactant expression. Tumors with a high surfactant expression displayed a transcriptomic profile of an inflammatory microenvironment. Conclusions: The expression of surfactant metabolism-related genes (SFTPA1, SFTPB, and NAPSA) defines an inflamed subtype of lung adenocarcinoma brain metastases characterized by high abundance of TILs in close vicinity to tumor cells, a prolonged survival, and a tumor microenvironment which might be more accessible to immunotherapeutic approaches. Full Article
brain Somatic Copy-Number Alterations Contribute to Brain Metastasis [Metastasis] By cancerdiscovery.aacrjournals.org Published On :: 2020-05-01T00:05:26-07:00 In lung cancer, brain metastasis was associated with somatic amplification of MYC, YAP1, or MMP13. Full Article
brain Glial TIM-3 Modulates Immune Responses in the Brain Tumor Microenvironment By cancerres.aacrjournals.org Published On :: 2020-05-04T05:35:17-07:00 T-cell immunoglobulin and mucin domain–containing molecule 3 (TIM-3), a potential immunotherapeutic target for cancer, has been shown to display diverse characteristics in a context-dependent manner. Thus, it would be useful to delineate the precise functional features of TIM-3 in a given situation. Here, we report that glial TIM-3 shows distinctive properties in the brain tumor microenvironment. TIM-3 was expressed on both growing tumor cells and their surrounding cells including glia and T cells in an orthotopic mouse glioma model. The expression pattern of TIM-3 was distinct from those of other immune checkpoint molecules in tumor-exposed and tumor-infiltrating glia. Comparison of cells from tumor-bearing and contralateral hemispheres of a glioma model showed that TIM-3 expression was lower in tumor-infiltrating CD11b+CD45mid glial cells but higher in tumor-infiltrating CD8+ T cells. In TIM-3 mutant mice with intracellular signaling defects and Cre-inducible TIM-3 mice, TIM-3 affected the expression of several immune-associated molecules including iNOS and PD-L1 in primary glia-exposed conditioned media (CM) from brain tumors. Further, TIM-3 was cross-regulated by TLR2, but not by TLR4, in brain tumor CM- or Pam3CSK4-exposed glia. In addition, following exposure to tumor CM, IFNγ production was lower in T cells cocultured with TIM-3–defective glia than with normal glia. Collectively, these findings suggest that glial TIM-3 actively and distinctively responds to brain tumor, and plays specific intracellular and intercellular immunoregulatory roles that might be different from TIM-3 on T cells in the brain tumor microenvironment.Significance:TIM-3 is typically thought of as a T-cell checkpoint receptor. This study demonstrates a role for TIM-3 in mediating myeloid cell responses in glioblastoma. Full Article
brain [PERSPECTIVES] Brain Metastasis Organotropism By perspectivesinmedicine.cshlp.org Published On :: 2020-05-01T06:30:15-07:00 Brain metastases are associated with poor prognosis irrespective of the primary tumor they originate from. Current treatments for brain metastases are palliative, and patients with symptomatic brain metastasis have a one-year survival of <20%. Lung cancer, breast cancer, and melanoma have higher incidences of brain metastases compared with other types of cancers. However, it is not very clear why some cancers metastasize to the brain more frequently than others. Studies thus far suggest that brain-specific tropism of certain types of cancers is defined by a winning combination of the following factors: unique genetic subtypes of primary tumors or its subclones enabling detachment, dissemination, blood–brain barrier penetration, plus proliferation and survival in hypoxic low-glucose microenvironment; specific transcriptomic and epigenetic changes of colony-forming metastatic cells, allowing their outgrowth; favorable metastasis-permissive microenvironment of the brain created by interactions of cancer cells and cells in the brain through triggering inflammation, recruiting myeloid-derived suppressor cells, and promoting metabolic adaptation; immunosuppression resulting in the failure of adaptive immune response to recognize or kill cancer cells in the brain. Here, we briefly review recent advances in understanding brain metastasis organotropism and outline directions for future research. Full Article
brain Thalamic Massa Intermedia in Children with and without Midline Brain Malformations [PEDIATRICS] By www.ajnr.org Published On :: 2020-04-09T06:30:48-07:00 BACKGROUND AND PURPOSE: The massa intermedia is a normal midline transventricular thalamic connection. Massa intermedia aberrations are common in schizophrenia, Chiari II malformation, X-linked hydrocephalus, Cornelia de Lange syndrome, and diencephalic-mesencephalic junction dysplasia, among others. We have noticed that massa intermedia abnormalities often accompany other midline malformations. The massa intermedia has never been formally evaluated in a group of exclusively pediatric patients, to our knowledge. We sought to compare and contrast the prevalence, size, and location of the massa intermedia in pediatric patients with and without congenital midline brain abnormalities. MATERIALS AND METHODS: Successive 3T brain MR imaging examinations from pediatric patients with and without midline malformations were procured from the imaging data base at a pediatric hospital. Massa intermedia presence, size, morphology, and position were determined using 3D-TIWI with 1-mm isotropic resolution. The brain commissures, septum pellucidum, hypothalamus, hippocampus, vermis, and brain stem were evaluated to determine whether alterations were related to or predictive of massa intermedia abnormalities. RESULTS: The massa intermedia was more frequently absent, dysmorphic, and/or displaced in patients with additional midline abnormalities than in those without. The massa intermedia was absent in 40% of patients with midline malformations versus 12% of patients with normal findings (P < .001). Massa intermedia absence, surface area, and morphology were predictable by various attributes and alterations of the commissures, hippocampus, hypothalamus, vermis, brain stem, and third ventricle. CONCLUSIONS: Most pediatric patients have a thalamic massa intermedia centered in the anterior/superior third ventricle. Massa intermedia abnormalities are commonly associated with other midline malformations. Normal-variant massa intermedia absence is a diagnosis of exclusion. Full Article
brain Advanced ADC Histogram, Perfusion, and Permeability Metrics Show an Association with Survival and Pseudoprogression in Newly Diagnosed Diffuse Intrinsic Pontine Glioma: A Report from the Pediatric Brain Tumor Consortium [FUNCTIONAL] By www.ajnr.org Published On :: 2020-04-09T06:30:48-07:00 BACKGROUND AND PURPOSE: Diffuse intrinsic pontine glioma is a lethal childhood brain cancer with dismal prognosis and MR imaging is the primary methodology used for diagnosis and monitoring. Our aim was to determine whether advanced diffusion, perfusion, and permeability MR imaging metrics predict survival and pseudoprogression in children with newly diagnosed diffuse intrinsic pontine glioma. MATERIALS AND METHODS: A clinical trial using the poly (adenosine diphosphate ribose) polymerase (PARP) inhibitor veliparib concurrently with radiation therapy, followed by maintenance therapy with veliparib + temozolomide, in children with diffuse intrinsic pontine glioma was conducted by the Pediatric Brain Tumor Consortium. Standard MR imaging, DWI, dynamic contrast-enhanced perfusion, and DSC perfusion were performed at baseline and approximately every 2 months throughout treatment. ADC histogram metrics of T2-weighted FLAIR and enhancing tumor volume, dynamic contrast-enhanced permeability metrics for enhancing tumors, and tumor relative CBV from DSC perfusion MR imaging were calculated. Baseline values, post-radiation therapy changes, and longitudinal trends for all metrics were evaluated for associations with survival and pseudoprogression. RESULTS: Fifty children were evaluable for survival analyses. Higher baseline relative CBV was associated with shorter progression-free survival (P = .02, Q = 0.089) and overall survival (P = .006, Q = 0.055). Associations of higher baseline mean transfer constant from the blood plasma into the extravascular extracellular space with shorter progression-free survival (P = .03, Q = 0.105) and overall survival (P = .03, Q = 0.102) trended toward significance. An increase in relative CBV with time was associated with shorter progression-free survival (P < .001, Q < 0.001) and overall survival (P = .004, Q = 0.043). Associations of longitudinal mean extravascular extracellular volume fraction with progression-free survival (P = .03, Q = 0.104) and overall survival (P = .03, Q = 0.105) and maximum transfer constant from the blood plasma into the extravascular extracellular space with progression-free survival (P = .03, Q = 0.102) trended toward significance. Greater increases with time were associated with worse outcomes. True radiologic progression showed greater post-radiation therapy decreases in mode_ADC_FLAIR compared with pseudoprogression (means, –268.15 versus –26.11, P = .01.) CONCLUSIONS: ADC histogram, perfusion, and permeability MR imaging metrics in diffuse intrinsic pontine glioma are useful in predicting survival and pseudoprogression. Full Article
brain Treatment Outcomes of Endovascular Embolization Only in Patients with Unruptured Brain Arteriovenous Malformations: A Subgroup Analysis of ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations) [INTERVENTIONAL] By www.ajnr.org Published On :: 2020-04-09T06:30:48-07:00 BACKGROUND AND PURPOSE: Endovascular embolization only has been advocated for treatment of brain arteriovenous malformations in recent trials. Our aim was to evaluate the results of embolization only in a cohort of patients who were enrolled in the A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) study at 39 clinical sites in 9 countries. MATERIALS AND METHODS: We analyzed the rates and severity of stroke and death in patients who underwent embolization only. Events were identified through in-person neurologic follow-up visits performed at 6-month intervals during the first 2 years and annually, with telephone contact every 6 months thereafter. All event-related data were reviewed by independent adjudicators. RESULTS: Among 30 patients who had embolization planned, 26 underwent embolization only. A total of 13 stroke events were reported in the follow-up period among 26 subjects (ischemic, hemorrhagic, or both in 4, 7, and 2 subjects, respectively). The adverse event occurred after the first embolization in 11 of 13 patients. One patient had a major motor deficit, and 2 patients developed major visual field deficits. One event was fatal. The modified Rankin Scale score was 0–2 at last follow-up in 11 of the 12 stroke survivors. Estimated stroke-free survival was 46% at 12 months. CONCLUSIONS: Although the rates of stroke and/or death were high in patients treated with embolization only in ARUBA, the rates of favorable outcomes following stroke were high during follow-up. Full Article