Intranasal long R3 insulin-like growth factor-1 treatment promotes amyloid plaque remodeling in cerebral cortex but fails to preserve cognitive function in male 5XFAD mice.

Background: Insulin-like growth factor-1 (IGF-1) promotes neurogenesis, cell survival, and glial function, making it a promising candidate therapy in Alzheimer's disease (AD).

Objective: Long arginine 3-IGF-1 (LR3-IGF-1) is a potent IGF-1 analogue. We sought to determine whether intranasal (IN) LR3 treatment would delay cognitive decline and pathology in 5XFAD mice.

ANKS1B encoded AIDA-1 regulates social behaviors by controlling oligodendrocyte function.

Heterozygous deletions in the ANKS1B gene cause ANKS1B neurodevelopmental syndrome (ANDS), a rare genetic disease characterized by autism spectrum disorder (ASD), attention deficit/hyperactivity disorder, and speech and motor deficits. The ANKS1B gene encodes for AIDA-1, a protein that is enriched at neuronal synapses and regulates synaptic plasticity. Here we report an unexpected role for oligodendroglial deficits in ANDS pathophysiology.

Evolving brain and behaviour changes in rats following repetitive subconcussive head impacts.

There is growing concern that repetitive subconcussive head impacts, independent of concussion, alter brain structure and function, and may disproportionately affect the developing brain. Animal studies of repetitive subconcussive head impacts are needed to begin to characterize the pathological basis and mechanisms underlying imaging and functional effects of repetitive subconcussive head impacts seen in humans. Since repetitive subconcussive head impacts have been largely unexplored in animals, we aimed to characterize the evolution of imaging, behavioural and pathological effects of repetitive subconcussive head impacts in awake adolescent rodents.

Evidence for preserved insulin responsiveness in the aging rat brain.

Insulin appears to exert salutary effects in the central nervous system (CNS). Thus, brain insulin resistance has been proposed to play a role in brain aging and dementia but is conceptually complex and unlikely to fit classic definitions established in peripheral tissues. Thus, we sought to characterize brain insulin responsiveness in young (4-5 months) and old (24 months) FBN male rats using a diverse set of assays to determine the extent to which insulin effects in the CNS are impaired with age.

Corrected cerebral blood flow and reduced cerebral inflammation in berk sickle mice with higher fetal hemoglobin.

Fetal hemoglobin (HbF) is known to lessen the severity of sickle cell disease (SCD), through reductions in peripheral vaso-occlusive disease and reduced risk for cerebrovascular events. However, the influence of HbF on oxygen delivery to high metabolism tissues like the brain, or its influence on cerebral perfusion, metabolism, inflammation or function have not been widely studied. We employed a Berkley mouse model (BERK) of SCD with gamma transgenes q3 expressing exclusively human α- and β-globins with varying levels of γ globin expression to investigate the effect of HbF expression on the brain using magnetic resonance imaging (MRI), MRI diffusion tensor imaging (DTI) and spectroscopy (MRS) and hematological parameters.

Quercetin Completely Ameliorates Hypoxia-Reoxygenation-Induced Pathophysiology Severity in NY1DD Transgenic Sickle Mice: Intrinsic Mild Steady State Pathophysiology of the Disease in NY1DD Is Also Reversed.

The vaso-occlusive crisis (VOC) is a major complication of sickle cell disease (SCD); thus, strategies to ameliorate vaso-occlusive episodes are greatly needed. We evaluated the therapeutic benefits of quercetin in a SCD transgenic sickle mouse model. This disease model exhibited very mild disease pathophysiology in the steady state.

Defective myelination in an RNA polymerase III mutant leukodystrophic mouse.

RNA polymerase (Pol) III synthesizes abundant short noncoding RNAs that have essential functions in protein synthesis, secretion, and other processes. Despite the ubiquitous functions of these RNAs, mutations in Pol III subunits cause Pol III-related leukodystrophy, an early-onset neurodegenerative disease. The basis of this neural sensitivity and the mechanisms of disease pathogenesis are unknown.

Associations of Maternal Prenatal Drug Abuse With Measures of Newborn Brain Structure, Tissue Organization, and Metabolite Concentrations.

Importance: Increasing rates of illicit drug use during pregnancy may be associated with risk for long-term health problems in prenatally exposed children.

Objective: To identify the associations of prenatal exposure to illicit drugs with organization of the newborn brain.

Design, Setting, And Participants: For this cohort study, a volunteer sample of 210 illicit drug-using and nonusing mothers and their newborns was enrolled from prenatal clinics and drug abuse treatment programs in New York, New York.

Diffusion Tensor Imaging of the Evolving Response to Mild Traumatic Brain Injury in Rats.

Mild traumatic brain injury (mTBI), also known as concussion, is a serious public health challenge. Although most patients recover, a substantial minority suffers chronic disability. The mechanisms underlying mTBI-related detrimental effects remain poorly understood.

Central IGF-1 protects against features of cognitive and sensorimotor decline with aging in male mice.

Disruptions in growth hormone/insulin-like growth factor-1 (GH/IGF-1) signaling have been linked to improved longevity in mice and humans. Nevertheless, while IGF-1 levels are associated with increased cancer risk, they have been paradoxically implicated with protection from other age-related conditions, particularly in the brain, suggesting that strategies aimed at selectively increasing central IGF-1 action may have favorable effects on aging. To test this hypothesis, we generated inducible, brain-specific (TRE-IGF-1 × Camk2a-tTA) IGF-1 (bIGF-1) overexpression mice and studied effects on healthspan.

Animal models of closed-skull, repetitive mild traumatic brain injury.

The underlying mechanisms that result in neurophysiological changes and cognitive sequelae in the context of repetitive mild traumatic brain injury (rmTBI) remain poorly understood. Animal models provide a unique opportunity to examine cellular and molecular responses using histological assessment, which can give important insights on the neurophysiological changes associated with the evolution of brain injury. To better understand the potential cumulative effects of multiple concussions, the focus of animal models is shifting from single to repetitive head impacts.

The neurobiological effects of repetitive head impacts in collision sports.

It is now recognized that repetitive head impacts (RHI) in sport have the potential for long-term neurological impairments. In order to identify targets for intervention and/or pharmacological treatment, it is necessary to characterize the neurobiological mechanisms associated with RHI. This review aims to summarize animal and human studies that specifically address Blood Brain Barrier (BBB) dysfunction, abnormal neuro-metabolic and neuro-inflammatory processes as well as Tau aggregation associated with RHI in collision sports.

Brain neurochemical and hemodynamic findings in the NY1DD mouse model of mild sickle cell disease.

To characterize the cerebral profile associated with sickle cell disease (SCD), we used in vivo proton MRI and MRS to quantify hemodynamics and neurochemicals in the thalamus of NY1DD mice, a mild model of SCD, and compared them with wild-type (WT) control mice. Compared with WT mice, NY1DD mice at steady state had elevated cerebral blood flow (CBF) and concentrations of N-acetylaspartate (NAA), glutamate (Glu), alanine, total creatine and N-acetylaspartylglutamate. Concentrations of glutathione (GSH) at steady state showed a negative correlation with BOLD signal change in response to 100% oxygen, a marker for oxidative stress, and mean diffusivity assessed using diffusion-tensor imaging, a marker for edematous inflammation.

Two step Gaussian mixture model approach to characterize white matter disease based on distributional changes.

Background: Magnetic resonance imaging reveals macro- and microstructural correlates of neurodegeneration, which are often assessed using voxel-by-voxel t-tests for comparing mean image intensities measured by fractional anisotropy (FA) between cases and controls or regression analysis for associating mean intensity with putative risk factors. This analytic strategy focusing on mean intensity in individual voxels, however, fails to account for change in distribution of image intensities due to disease.

New Method: We propose a method that aims to facilitate simple and clear characterization of underlying distribution.

A simple method for determining the coagulation threshold temperature of transparent tissue-mimicking thermal therapy gel phantoms: Validated by magnetic resonance imaging thermometry.

Purpose: Tissue-mimicking thermal therapy phantoms that coagulate at specific temperatures are valuable tools for developing and evaluating treatment strategies related to thermal therapy. Here, the authors propose a simple and efficient method for determining the coagulation threshold temperature of transparent thermal therapy gel phantoms.

Methods: The authors used a previously published gel phantom recipe with 2% (w/v) of bovine serum albumin as the temperature-sensitive protein.

AAVP displaying octreotide for ligand-directed therapeutic transgene delivery in neuroendocrine tumors of the pancreas.

Patients with inoperable or unresectable pancreatic neuroendocrine tumors (NETs) have limited treatment options. These rare human tumors often express somatostatin receptors (SSTRs) and thus are clinically responsive to certain relatively stable somatostatin analogs, such as octreotide. Unfortunately, however, this tumor response is generally short-lived.

In vivo (1)H MRS and (31)P MRSI of the response to cyclocreatine in transgenic mouse liver expressing creatine kinase.

Hepatocyte transplantation has been explored as a therapeutic alternative to liver transplantation, but a means to monitor the success of the procedure is lacking. Published findings support the use of in vivo (31)P MRSI of creatine kinase (CK)-expressing hepatocytes to monitor proliferation of implanted hepatocytes. Phosphocreatine tissue level depends upon creatine (Cr) input to the CK enzyme reaction, but Cr measurement by (1)H MRS suffers from low signal-to-noise ratio (SNR).

Subcortical structure alterations impact language processing in individuals with schizophrenia and those at high genetic risk.

Objective: Cortical structural and functional anomalies have been found to associate with language impairments in both schizophrenia patients and genetic high risk individuals for developing schizophrenia. However, subcortical structures that contribute to language processing haven't been well studied in this population, and thus became the main objective of this study.

Method: We examined structural MRI data from 20 patients with schizophrenia, 21 individuals at genetic high risk, and 48 controls.

Phenotypic characterization of a Csf1r haploinsufficient mouse model of adult-onset leukodystrophy with axonal spheroids and pigmented glia (ALSP).

Mutations in the colony stimulating factor-1 receptor (CSF1R) that abrogate the expression of the affected allele or lead to the expression of mutant receptor chains devoid of kinase activity have been identified in both familial and sporadic cases of ALSP. To determine the validity of the Csf1r heterozygous mouse as a model of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) we performed behavioral, radiologic, histopathologic, ultrastructural and cytokine expression studies of young and old Csf1r+/- and control Csf1r+/+ mice. Six to 8-month old Csf1r+/- mice exhibit cognitive deficits, and by 9-11 months develop sensorimotor deficits and in male mice, depression and anxiety-like behavior.

In vivo proton MR spectroscopy of pancreatic neuroendocrine tumors in a multiple endocrine neoplasia type 1 conditional knockout mouse model.

Purpose: MR spectroscopy (MRS) can improve diagnosis and follow treatment in cancer. However, no study has yet reported application of in vivo (1)H-MRS in malignant pancreatic lesions. This study quantitatively determined whether in vivo (1)H-MRS on multiple endocrine neoplasia type 1 (Men1) conditional knockout (KO) mice and their wild type (WT) littermates could detect differences in total choline (tCho) levels between tumor and control pancreas.

A gaussian mixture model approach for estimating and comparing the shapes of distributions of neuroimaging data: diffusion-measured aging effects in brain white matter.

Neuroimaging signal intensity measures underlying physiology at each voxel unit. The brain-wide distribution of signal intensities may be used to assess gross brain abnormality. To compare distributions of brain image data between groups, t-tests are widely applied.

Soccer heading is associated with white matter microstructural and cognitive abnormalities.

Purpose: To investigate the association of soccer heading with subclinical evidence of traumatic brain injury.

Materials And Methods: With institutional review board approval and compliance with HIPAA guidelines, 37 amateur soccer players (mean age, 30.9 years; 78% [29] men, 22% [eight] women) gave written informed consent and completed a questionnaire to quantify heading in the prior 12 months and lifetime concussions.

Whole brain approaches for identification of microstructural abnormalities in individual patients: comparison of techniques applied to mild traumatic brain injury.

Purpose: Group-wise analyses of DTI in mTBI have demonstrated evidence of traumatic axonal injury (TAI), associated with adverse clinical outcomes. Although mTBI is likely to have a unique spatial pattern in each patient, group analyses implicitly assume that location of injury will be the same across patients. The purpose of this study was to optimize and validate a procedure for analysis of DTI images acquired in individual patients, which could detect inter-individual differences and be applied in the clinical setting, where patients must be assessed as individuals.

Unique topology of language processing brain network: a systems-level biomarker of schizophrenia.

Objective: Schizophrenia is a severe and heritable brain disorder. Language impairment has been hypothesized to spur its onset and underlie the characteristic symptoms. In this study, we investigate whether altered topological pattern of the language processing brain network exists and could be a potential biomarker of schizophrenia.