Studying the Brain in a Dish: 3D Cell Culture Models of Human Brain Development and Disease.

PubMed

Brown, Juliana; Quadrato, Giorgia; Arlotta, Paola

2018-01-01

The study of the cellular and molecular processes of the developing human brain has been hindered by access to suitable models of living human brain tissue. Recently developed 3D cell culture models offer the promise of studying fundamental brain processes in the context of human genetic background and species-specific developmental mechanisms. Here, we review the current state of 3D human brain organoid models and consider their potential to enable investigation of complex aspects of human brain development and the underpinning of human neurological disease. © 2018 Elsevier Inc. All rights reserved.

Coupling of transient near infrared photonic with magnetic nanoparticle for potential dissipation-free biomedical application in brain

PubMed Central

Sagar, Vidya; Atluri, V. S. R.; Tomitaka, A.; Shah, P.; Nagasetti, A.; Pilakka-Kanthikeel, S.; El-Hage, N.; McGoron, A.; Takemura, Y.; Nair, M.

2016-01-01

Combined treatment strategies based on magnetic nanoparticles (MNPs) with near infrared ray (NIR) biophotonic possess tremendous potential for non-invasive therapeutic approach. Nonetheless, investigations in this direction have been limited to peripheral body region and little is known about the potential biomedical application of this approach for brain. Here we report that transient NIR exposure is dissipation-free and has no adverse effect on the viability and plasticity of major brain cells in the presence or absence superparamagnetic nanoparticles. The 808 nm NIR laser module with thermocouple was employed for functional studies upon NIR exposure to brain cells. Magnetic nanoparticles were characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD), dynamic laser scattering (DLS), and vibrating sample magnetometer (VSM). Brain cells viability and plasticity were analyzed using electric cell-substrate impedance sensing system, cytotoxicity evaluation, and confocal microscopy. When efficacious non-invasive photobiomodulation and neuro-therapeutical targeting and monitoring to brain remain a formidable task, the discovery of this dissipation-free, transient NIR photonic approach for brain cells possesses remarkable potential to add new dimension. PMID:27465276

Coupling of transient near infrared photonic with magnetic nanoparticle for potential dissipation-free biomedical application in brain.

PubMed

Sagar, Vidya; Atluri, V S R; Tomitaka, A; Shah, P; Nagasetti, A; Pilakka-Kanthikeel, S; El-Hage, N; McGoron, A; Takemura, Y; Nair, M

2016-07-28

Combined treatment strategies based on magnetic nanoparticles (MNPs) with near infrared ray (NIR) biophotonic possess tremendous potential for non-invasive therapeutic approach. Nonetheless, investigations in this direction have been limited to peripheral body region and little is known about the potential biomedical application of this approach for brain. Here we report that transient NIR exposure is dissipation-free and has no adverse effect on the viability and plasticity of major brain cells in the presence or absence superparamagnetic nanoparticles. The 808 nm NIR laser module with thermocouple was employed for functional studies upon NIR exposure to brain cells. Magnetic nanoparticles were characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD), dynamic laser scattering (DLS), and vibrating sample magnetometer (VSM). Brain cells viability and plasticity were analyzed using electric cell-substrate impedance sensing system, cytotoxicity evaluation, and confocal microscopy. When efficacious non-invasive photobiomodulation and neuro-therapeutical targeting and monitoring to brain remain a formidable task, the discovery of this dissipation-free, transient NIR photonic approach for brain cells possesses remarkable potential to add new dimension.

Coupling of transient near infrared photonic with magnetic nanoparticle for potential dissipation-free biomedical application in brain

NASA Astrophysics Data System (ADS)

Sagar, Vidya; Atluri, V. S. R.; Tomitaka, A.; Shah, P.; Nagasetti, A.; Pilakka-Kanthikeel, S.; El-Hage, N.; McGoron, A.; Takemura, Y.; Nair, M.

2016-07-01

Combined treatment strategies based on magnetic nanoparticles (MNPs) with near infrared ray (NIR) biophotonic possess tremendous potential for non-invasive therapeutic approach. Nonetheless, investigations in this direction have been limited to peripheral body region and little is known about the potential biomedical application of this approach for brain. Here we report that transient NIR exposure is dissipation-free and has no adverse effect on the viability and plasticity of major brain cells in the presence or absence superparamagnetic nanoparticles. The 808 nm NIR laser module with thermocouple was employed for functional studies upon NIR exposure to brain cells. Magnetic nanoparticles were characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD), dynamic laser scattering (DLS), and vibrating sample magnetometer (VSM). Brain cells viability and plasticity were analyzed using electric cell-substrate impedance sensing system, cytotoxicity evaluation, and confocal microscopy. When efficacious non-invasive photobiomodulation and neuro-therapeutical targeting and monitoring to brain remain a formidable task, the discovery of this dissipation-free, transient NIR photonic approach for brain cells possesses remarkable potential to add new dimension.

Emotional sounds and the brain: the neuro-affective foundations of musical appreciation.

PubMed

Panksepp, Jaak; Bernatzky, Günther

2002-11-01

This article summarizes the potential role of evolved brain emotional systems in the mediation of music appreciation. A variety of examples of how music may promote behavioral change are summarized, including effects on memory, mood, brain activity as well as autonomic responses such as the experience of 'chills'. Studies on animals (e.g. young chicks) indicate that musical stimulation have measurable effects on their behaviors and brain chemistries, especially increased brain norepinephrine (NE) turnover. The evolutionary sources of musical sensitivity are discussed, as well as the potential medical-therapeutic implications of this knowledge.

Potential subjects' responses to an ethics questionnaire in a phase I study of deep brain stimulation in early Parkinson's disease.

PubMed

Finder, Stuart G; Bliton, Mark J; Gill, Chandler E; Davis, Thomas L; Konrad, Peter E; Charles, P David

2012-01-01

Central to ethically justified clinical trial design is the need for an informed consent process responsive to how potential subjects actually comprehend study participation, especially study goals, risks, and potential benefits. This will be particularly challenging when studying deep brain stimulation and whether it impedes symptom progression in Parkinson's disease, since potential subjects will be Parkinson's patients for whom deep brain stimulation will likely have therapeutic value in the future as their disease progresses. As part of an expanded informed consent process for a pilot Phase I study of deep brain stimulation in early stage Parkinson's disease, an ethics questionnaire composed of 13 open-ended questions was distributed to potential subjects. The questionnaire was designed to guide potential subjects in thinking about their potential participation. While the purpose of the study (safety and tolerability) was extensively presented during the informed consent process, in returned responses 70 percent focused on effectiveness and 91 percent included personal benefit as poten- tial benefit from enrolling. However, 91 percent also indicated helping other Parkinson's patients as motivation when considering whether or not to enroll. This combination of responses highlights two issues to which investigators need to pay close attention in future trial designs: (1) how, and in what ways, informed consent processes reinforce potential subjects' preconceived understandings of benefit, and (2) that potential subjects see themselves as part of a community of Parkinson's sufferers with responsibilities extending beyond self-interest. More importantly, it invites speculation that a different paradigm for informed consent may be needed.

The Use of Event-Related Brain Potentials to Measure Cognitive Processing Deficits in the Brain-Injured.

ERIC Educational Resources Information Center

Torello, Michael W., Jr.; And Others

Until recently it has been possible only to measure the behavioral products of cognitive processing, e.g. reaction time. However, this is a rather indirect way of studying brain substrates of cognition. Psychophysiological techniques can be used to study the neural mechanisms of cognition. In this experiment brain electrical activity was measured…

Limitations on the Developing Preterm Brain: Impact of Periventricular White Matter Lesions on Brain Connectivity and Cognition

ERIC Educational Resources Information Center

Pavlova, Marina A.; Krageloh-Mann, Ingeborg

2013-01-01

Brain lesions to the white matter in peritrigonal regions, periventricular leukomalacia, in children who were born prematurely represent an important model for studying limitations on brain development. The lesional pattern is of early origin and bilateral, that constrains the compensatory potential of the brain. We suggest that (i) topography and…

Mapping Language Function in the Brain: A Review of the Recent Literature.

ERIC Educational Resources Information Center

Crafton, Robert E.; Kido, Elissa

2000-01-01

Considers the potential importance of brain study for composition instruction, briefly describes functional imaging techniques, and reviews the findings of recent brain-mapping studies investigating the neurocognitive systems involved in language function. Presents a review of the recent literature and considers the possible implications of this…

The Potential of Using Brain Images for Authentication

PubMed Central

Zhou, Zongtan; Shen, Hui; Hu, Dewen

2014-01-01

Biometric recognition (also known as biometrics) refers to the automated recognition of individuals based on their biological or behavioral traits. Examples of biometric traits include fingerprint, palmprint, iris, and face. The brain is the most important and complex organ in the human body. Can it be used as a biometric trait? In this study, we analyze the uniqueness of the brain and try to use the brain for identity authentication. The proposed brain-based verification system operates in two stages: gray matter extraction and gray matter matching. A modified brain segmentation algorithm is implemented for extracting gray matter from an input brain image. Then, an alignment-based matching algorithm is developed for brain matching. Experimental results on two data sets show that the proposed brain recognition system meets the high accuracy requirement of identity authentication. Though currently the acquisition of the brain is still time consuming and expensive, brain images are highly unique and have the potential possibility for authentication in view of pattern recognition. PMID:25126604

The potential of using brain images for authentication.

PubMed

Chen, Fanglin; Zhou, Zongtan; Shen, Hui; Hu, Dewen

2014-01-01

Biometric recognition (also known as biometrics) refers to the automated recognition of individuals based on their biological or behavioral traits. Examples of biometric traits include fingerprint, palmprint, iris, and face. The brain is the most important and complex organ in the human body. Can it be used as a biometric trait? In this study, we analyze the uniqueness of the brain and try to use the brain for identity authentication. The proposed brain-based verification system operates in two stages: gray matter extraction and gray matter matching. A modified brain segmentation algorithm is implemented for extracting gray matter from an input brain image. Then, an alignment-based matching algorithm is developed for brain matching. Experimental results on two data sets show that the proposed brain recognition system meets the high accuracy requirement of identity authentication. Though currently the acquisition of the brain is still time consuming and expensive, brain images are highly unique and have the potential possibility for authentication in view of pattern recognition.

MicroRNAs in brain metastases: potential role as diagnostics and therapeutics.

PubMed

Alsidawi, Samer; Malek, Ehsan; Driscoll, James J

2014-06-11

Brain metastases remain a daunting adversary that negatively impact patient survival. Metastatic brain tumors affect up to 45% of all cancer patients with systemic cancer and account for ~20% of all cancer-related deaths. A complex network of non-coding RNA molecules, microRNAs (miRNAs), regulate tumor metastasis. The brain micro-environment modulates metastatic tumor growth; however, defining the precise genetic events that promote metastasis in the brain niche represents an important, unresolved problem. Understanding these events will reveal disease-based targets and offer effective strategies to treat brain metastases. Effective therapeutic strategies based upon the biology of brain metastases represent an urgent, unmet need with immediate potential for clinical impact. Studies have demonstrated the ability of miRNAs to distinguish normal from cancerous cells, primary from secondary brain tumors, and correctly categorize metastatic brain tumor tissue of origin based solely on miRNA profiles. Interestingly, manipulation of miRNAs has proven effective in cancer treatment. With the promise of reduced toxicity, increased efficacy and individually directed personalized anti-cancer therapy, using miRNA in the treatment of metastatic brain tumors may prove very useful and improve patient outcome. In this review, we focus on the potential of miRNAs as diagnostic and therapeutic targets for the treatment of metastatic brain lesions.

Do antipsychotic drugs affect brain structure? A systematic and critical review of MRI findings.

PubMed

Navari, S; Dazzan, P

2009-11-01

The potential effects of antipsychotic drugs on brain structure represent a key factor in understanding neuroanatomical changes in psychosis. This review addresses two issues: (1) do antipsychotic medications induce changes in total or regional human brain volumes and (2) do such effects depend on antipsychotic type? A systematic review of studies reporting structural brain magnetic resonance imaging (MRI) measures: (1) directly in association with antipsychotic use; and (2) in patients receiving lifetime treatment with antipsychotics in comparison with drug-naive patients or healthy controls. We searched Medline and EMBASE databases using the medical subject heading terms: 'antipsychotics' AND 'brain' AND (MRI NOT functional). The search included studies published up to 31 January 2007. Wherever possible, we reported the effect size of the difference observed. Thirty-three studies met our inclusion criteria. The results suggest that antipsychotics act regionally rather than globally on the brain. These volumetric changes are of a greater magnitude in association with typical than with atypical antipsychotic use. Indeed, there is evidence of a specific effect of antipsychotic type on the basal ganglia, with typicals specifically increasing the volume of these structures. Differential effects of antipsychotic type may also be present on the thalamus and the cortex, but data on these and other brain areas are more equivocal. Antipsychotic treatment potentially contributes to the brain structural changes observed in psychosis. Future research should take into account these potential effects, and use adequate sample sizes, to allow improved interpretation of neuroimaging findings in these disorders.

Time-resolved fluorescence spectroscopy of human brain tumors

NASA Astrophysics Data System (ADS)

Marcu, Laura; Thompson, Reid C.; Garde, Smita; Sedrak, Mark; Black, Keith L.; Yong, William H.

2002-05-01

Fluorescence spectroscopy of the endogenous emission of brain tumors has been researched as a potentially important method for the intraoperative localization of brain tumor margins. In this study, we investigate the use of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) for demarcation of primary brain tumors by studying the time-resolved spectra of gliomas of different histologic grades. Time-resolved fluorescence (3 ns, 337 nm excitation) from excised human brain tumor show differences between the time-resolved emission of malignant glioma and normal brain tissue (gray and white matter). Our findings suggest that brain tumors can be differentiated from normal brain tissue based upon unique time-resolved fluorescence signature.

Non-invasive measurement of brain glycogen by NMR spectroscopy and its application to the study of brain metabolism

PubMed Central

Tesfaye, Nolawit; Seaquist, Elizabeth R.; Öz, Gülin

2011-01-01

Glycogen is the reservoir for glucose in the brain. Beyond the general agreement that glycogen serves as an energy source in the central nervous system, its exact role in brain energy metabolism has yet to be elucidated. Experiments performed in cell and tissue culture and animals have shown that glycogen content is affected by several factors including glucose, insulin, neurotransmitters, and neuronal activation. The study of in vivo glycogen metabolism has been hindered by the inability to measure glycogen non-invasively, but in the past several years, the development of a non-invasive localized 13C nuclear magnetic resonance (NMR) spectroscopy method has enabled the study of glycogen metabolism in the conscious human. With this technique, 13C-glucose is administered intravenously and its incorporation into and wash-out from brain glycogen is tracked. One application of this method has been to the study of brain glycogen metabolism in humans during hypoglycemia: data have shown that mobilization of brain glycogen is augmented during hypoglycemia and, after a single episode of hypoglycemia, glycogen synthesis rate is increased, suggesting that glycogen stores rebound to levels greater than baseline. Such studies suggest glycogen may serve as a potential energy reservoir in hypoglycemia and may participate in the brain's adaptation to recurrent hypoglycemia and eventual development of hypoglycemia unawareness. Beyond this focused area of study, 13C NMR spectroscopy has a broad potential for application in the study of brain glycogen metabolism and carries the promise of a better understanding of the role of brain glycogen in diabetes and other conditions. PMID:21732401

Visualizing Neuroscience: Learning about the Brain through Art

ERIC Educational Resources Information Center

Chudler, Eric H.; Konrady, Paula

2006-01-01

Neuroscience is a subject that can motivate, excite, and stimulate the curiosity of everyone However, the study of the brain is made difficult by an abundance of new vocabulary words and abstract concepts. Although neuroscience has the potential to inspire students, many teachers find it difficult to include a study of the brain in their…

Stem cell-based therapies for tumors in the brain: are we there yet?

PubMed Central

Shah, Khalid

2016-01-01

Advances in understanding adult stem cell biology have facilitated the development of novel cell-based therapies for cancer. Recent developments in conventional therapies (eg, tumor resection techniques, chemotherapy strategies, and radiation therapy) for treating both metastatic and primary tumors in the brain, particularly glioblastoma have not resulted in a marked increase in patient survival. Preclinical studies have shown that multiple stem cell types exhibit inherent tropism and migrate to the sites of malignancy. Recent studies have validated the feasibility potential of using engineered stem cells as therapeutic agents to target and eliminate malignant tumor cells in the brain. This review will discuss the recent progress in the therapeutic potential of stem cells for tumors in the brain and also provide perspectives for future preclinical studies and clinical translation. PMID:27282399

Breath-holding spells may be associated with maturational delay in myelination of brain stem.

PubMed

Vurucu, Sebahattin; Karaoglu, Abdulbaki; Paksu, Sukru M; Oz, Oguzhan; Yaman, Halil; Gulgun, Mustafa; Babacan, Oguzhan; Unay, Bulent; Akin, Ridvan

2014-02-01

To evaluate possible contribution of maturational delay of brain stem in the etiology of breath-holding spells in children using brain stem auditory evoked potentials. The study group included children who experienced breath-holding spells. The control group consisted of healthy age- and sex-matched children. Age, gender, type and frequency of spell, hemoglobin, and ferritin levels in study group and brain stem auditory evoked potentials results in both groups were recorded. Study group was statistically compared with control group for brain stem auditory evoked potentials. The mean age of study and control groups was 26.3 ± 14.6 and 28.9 ± 13.9 months, respectively. The III-V and I-V interpeak latencies were significantly prolonged in the study group compared with the control group (2.07 ± 0.2 milliseconds; 1.92 ± 0.13 milliseconds and 4.00 ± 0.27 milliseconds; 3.83 ± 0.19 milliseconds; P = 0.009 and P = 0.03, respectively). At the same time, III-V and I-V interpeak latencies of patients without anemia in the study group compared with those of control group were significantly prolonged (2.09 ± 0.24 milliseconds; 1.92 ± 0.13 milliseconds and 4.04 ± 0.28 milliseconds; 3.83 ± 0.19 milliseconds; P = 0.007 and P = 0.01, respectively). Our results consider that maturational delay in myelination of brain stem may have a role in the etiology of breath-holding spells in children.

Altered spontaneous brain activity in Cushing's disease: a resting-state functional MRI study.

PubMed

Jiang, Hong; He, Na-Ying; Sun, Yu-Hao; Jian, Fang-Fang; Bian, Liu-Guan; Shen, Jian-Kang; Yan, Fu-Hua; Pan, Si-Jian; Sun, Qing-Fang

2017-03-01

Cushing's disease (CD) provides a unique and naturalist model for studying the influence of hypercortisolism on the human brain and the reversibility of these effects after resolution of the condition. This cross-sectional study used resting-state fMRI (rs-fMRI) to investigate the altered spontaneous brain activity in CD patients and the trends for potential reversibility after the resolution of the hypercortisolism. We also aim to determine the relationship of these changes with clinical characteristics and cortisol levels. Active CD patients (n = 18), remitted CD patients (n = 14) and healthy control subjects (n = 22) were included in this study. Amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values were calculated to represent spontaneous brain activity. Our study resulted in three major findings: (i) active CD patients showed significantly altered spontaneous brain activity in the posterior cingulate cortex (PCC)/precuneus (PCu), occipital lobe (OC)/cerebellum, thalamus, right postcentral gyrus (PoCG) and left prefrontal cortex (PFC); (ii) trends for partial restoration of altered spontaneous brain activity after the resolution hypercortisolism were found in several brain regions; and (iii) active CD patients showed a significant correlation between cortisol levels and ALFF/ReHo values in the PCC/PCu, a small cluster in the OC and the right IPL. This study provides a new approach to investigating brain function abnormalities in patients with CD and enhances our understanding of the effect of hypercortisolism on the human brain. Furthermore, our explorative potential reversibility study of patients with CD may facilitate the development of future longitudinal studies. © 2016 John Wiley & Sons Ltd.

Morphological Encoding in German Children's Language Production: Evidence from Event-Related Brain Potentials

ERIC Educational Resources Information Center

Jessen, Anna; Fleischhauer, Elisabeth; Clahsen, Harald

2017-01-01

This study reports developmental changes in morphological encoding across late childhood. We examined event-related brain potentials (ERPs) during the silent production of regularly vs. irregularly inflected verb forms (viz. "-t" vs. "-n" participles of German) in groups of eight- to ten-year-olds, eleven- to…

Effects of Grammatical Categories on Children's Visual Language Processing: Evidence from Event-Related Brain Potentials

ERIC Educational Resources Information Center

Weber-Fox, Christine; Hart, Laura J.; Spruill, John E., III

2006-01-01

This study examined how school-aged children process different grammatical categories. Event-related brain potentials elicited by words in visually presented sentences were analyzed according to seven grammatical categories with naturally varying characteristics of linguistic functions, semantic features, and quantitative attributes of length and…

Toward FRP-Based Brain-Machine Interfaces—Single-Trial Classification of Fixation-Related Potentials

PubMed Central

Finke, Andrea; Essig, Kai; Marchioro, Giuseppe; Ritter, Helge

2016-01-01

The co-registration of eye tracking and electroencephalography provides a holistic measure of ongoing cognitive processes. Recently, fixation-related potentials have been introduced to quantify the neural activity in such bi-modal recordings. Fixation-related potentials are time-locked to fixation onsets, just like event-related potentials are locked to stimulus onsets. Compared to existing electroencephalography-based brain-machine interfaces that depend on visual stimuli, fixation-related potentials have the advantages that they can be used in free, unconstrained viewing conditions and can also be classified on a single-trial level. Thus, fixation-related potentials have the potential to allow for conceptually different brain-machine interfaces that directly interpret cortical activity related to the visual processing of specific objects. However, existing research has investigated fixation-related potentials only with very restricted and highly unnatural stimuli in simple search tasks while participant’s body movements were restricted. We present a study where we relieved many of these restrictions while retaining some control by using a gaze-contingent visual search task. In our study, participants had to find a target object out of 12 complex and everyday objects presented on a screen while the electrical activity of the brain and eye movements were recorded simultaneously. Our results show that our proposed method for the classification of fixation-related potentials can clearly discriminate between fixations on relevant, non-relevant and background areas. Furthermore, we show that our classification approach generalizes not only to different test sets from the same participant, but also across participants. These results promise to open novel avenues for exploiting fixation-related potentials in electroencephalography-based brain-machine interfaces and thus providing a novel means for intuitive human-machine interaction. PMID:26812487

Changing Brain Networks Through Non-invasive Neuromodulation

PubMed Central

To, Wing Ting; De Ridder, Dirk; Hart Jr., John; Vanneste, Sven

2018-01-01

Background/Objective: Non-invasive neuromodulation techniques, such as repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS), have increasingly been investigated for their potential as treatments for neurological and psychiatric disorders. Despite widespread dissemination of these techniques, the underlying therapeutic mechanisms and the ideal stimulation site for a given disorder remain unknown. Increasing evidence support the possibility of non-invasive neuromodulation affecting a brain network rather than just the local stimulation target. In this article, we present evidence in a clinical setting to support the idea that non-invasive neuromodulation changes brain networks. Method: This article addresses the idea that non-invasive neuromodulation modulates brain networks, rather than just the local stimulation target, using neuromodulation studies in tinnitus and major depression as examples. We present studies that support this hypothesis from different perspectives. Main Results/Conclusion: Studies stimulating the same brain region, such as the dorsolateral prefrontal cortex (DLPFC), have shown to be effective for several disorders and studies using different stimulation sites for the same disorder have shown similar results. These findings, as well as results from studies investigating brain network connectivity on both macro and micro levels, suggest that non-invasive neuromodulation affects a brain network rather than just the local stimulation site targeted. We propose that non-invasive neuromodulation should be approached from a network perspective and emphasize the therapeutic potential of this approach through the modulation of targeted brain networks. PMID:29706876

Changing Brain Networks Through Non-invasive Neuromodulation.

PubMed

To, Wing Ting; De Ridder, Dirk; Hart, John; Vanneste, Sven

2018-01-01

Background/Objective : Non-invasive neuromodulation techniques, such as repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS), have increasingly been investigated for their potential as treatments for neurological and psychiatric disorders. Despite widespread dissemination of these techniques, the underlying therapeutic mechanisms and the ideal stimulation site for a given disorder remain unknown. Increasing evidence support the possibility of non-invasive neuromodulation affecting a brain network rather than just the local stimulation target. In this article, we present evidence in a clinical setting to support the idea that non-invasive neuromodulation changes brain networks. Method : This article addresses the idea that non-invasive neuromodulation modulates brain networks, rather than just the local stimulation target, using neuromodulation studies in tinnitus and major depression as examples. We present studies that support this hypothesis from different perspectives. Main Results/Conclusion : Studies stimulating the same brain region, such as the dorsolateral prefrontal cortex (DLPFC), have shown to be effective for several disorders and studies using different stimulation sites for the same disorder have shown similar results. These findings, as well as results from studies investigating brain network connectivity on both macro and micro levels, suggest that non-invasive neuromodulation affects a brain network rather than just the local stimulation site targeted. We propose that non-invasive neuromodulation should be approached from a network perspective and emphasize the therapeutic potential of this approach through the modulation of targeted brain networks.

Age, Intelligence, and Event-Related Brain Potentials during Late Childhood: A Longitudinal Study.

ERIC Educational Resources Information Center

Stauder, Johannes E. A.; van der Molen, Maurits W.; Molenaar, Peter C. M.

2003-01-01

Studied the relationship between event-related brain activity, age, and intelligence using a visual oddball task presented to girls at 9, 10, and 11 years of age. Findings for 26 girls suggest a qualitative shift in the relation between event-related brain activity and intelligence between 9 and 10 years of age. (SLD)

Intranasal delivery of quercetin-loaded mucoadhesive nanoemulsion for treatment of cerebral ischaemia.

PubMed

Ahmad, Niyaz; Ahmad, Rizwan; Naqvi, Atta Abbas; Alam, Md Aftab; Ashafaq, Mohammad; Abdur Rub, Rehan; Ahmad, Farhan Jalees

2018-06-01

Quercetin (QUR), as an antioxidant flavonoid, exhibits potential role in the amelioration of cerebral ischaemia; however, poor solubility as well as oral absorption results low serum and tissue levels for this drug. To enhance bioavailability, this study aims to prepare QUR nanoemulsions and administer via non-invasive nasal route in order to evaluate the drug targeting in brain. Quercetin mucoadhesive nanoemulsion (QMNE) was prepared (ionic gelation method) and optimized using various parameters, that is, particle size, entrapment efficiency, zeta potential and ex vivo permeation study. The results observed for optimized QMNE were as follows: mean globule size (91.63 ± 4.36 nm), zeta potential (-17.26 ± 1.04 mV), drug content (99.84 ± 0.34%) and viscosity (121 ± 13 cp). To evaluate the extent of bioavailability for QMNE via post-intranasal (i.n.) administration, Ultra performance liquid chromatography-mass spectroscopy (UPLC-ESI-Q-TOF-MS/MS)-based bioanalytical method was developed and validated for pharmacokinetics, biodistribution, brain-targeting efficiency (9333.33 ± 39.39%) and brain drug-targeting potential (2181.83 ± 5.69%) which revealed enhanced QUR brain bioavailability as compared to intravenous administration (i.v.). Furthermore, improved neurobehavioral activity (locomotor and grip strength), histopathology and reduced infarction volume effects were observed in middle cerebral artery occlusion (MCAO)-induced cerebral ischemic rats model after i.n. administration of QMNE. This study supports a significant role for QMNE in terms of high brain-targeting potential and formulation efficiency due to ease of access and effective targeting in brain.

Won't Get Fooled Again: An Event-Related Potential Study of Task and Repetition Effects on the Semantic Processing of Items without Semantics

ERIC Educational Resources Information Center

Laszlo, Sarah; Stites, Mallory; Federmeier, Kara D.

2012-01-01

A growing body of evidence suggests that semantic access is obligatory. Several studies have demonstrated that brain activity associated with semantic processing, measured in the N400 component of the event-related brain potential (ERP), is elicited even by meaningless, orthographically illegal strings, suggesting that semantic access is not gated…

A brain-region-based meta-analysis method utilizing the Apriori algorithm.

PubMed

Niu, Zhendong; Nie, Yaoxin; Zhou, Qian; Zhu, Linlin; Wei, Jieyao

2016-05-18

Brain network connectivity modeling is a crucial method for studying the brain's cognitive functions. Meta-analyses can unearth reliable results from individual studies. Meta-analytic connectivity modeling is a connectivity analysis method based on regions of interest (ROIs) which showed that meta-analyses could be used to discover brain network connectivity. In this paper, we propose a new meta-analysis method that can be used to find network connectivity models based on the Apriori algorithm, which has the potential to derive brain network connectivity models from activation information in the literature, without requiring ROIs. This method first extracts activation information from experimental studies that use cognitive tasks of the same category, and then maps the activation information to corresponding brain areas by using the automatic anatomical label atlas, after which the activation rate of these brain areas is calculated. Finally, using these brain areas, a potential brain network connectivity model is calculated based on the Apriori algorithm. The present study used this method to conduct a mining analysis on the citations in a language review article by Price (Neuroimage 62(2):816-847, 2012). The results showed that the obtained network connectivity model was consistent with that reported by Price. The proposed method is helpful to find brain network connectivity by mining the co-activation relationships among brain regions. Furthermore, results of the co-activation relationship analysis can be used as a priori knowledge for the corresponding dynamic causal modeling analysis, possibly achieving a significant dimension-reducing effect, thus increasing the efficiency of the dynamic causal modeling analysis.

Tuning Up the Old Brain with New Tricks: Attention Training via Neurofeedback

PubMed Central

Jiang, Yang; Abiri, Reza; Zhao, Xiaopeng

2017-01-01

Neurofeedback (NF) is a form of biofeedback that uses real-time (RT) modulation of brain activity to enhance brain function and behavioral performance. Recent advances in Brain-Computer Interfaces (BCI) and cognitive training (CT) have provided new tools and evidence that NF improves cognitive functions, such as attention and working memory (WM), beyond what is provided by traditional CT. More published studies have demonstrated the efficacy of NF, particularly for treating attention deficit hyperactivity disorder (ADHD) in children. In contrast, there have been fewer studies done in older adults with or without cognitive impairment, with some notable exceptions. The focus of this review is to summarize current success in RT NF training of older brains aiming to match those of younger brains during attention/WM tasks. We also outline potential future advances in RT brainwave-based NF for improving attention training in older populations. The rapid growth in wireless recording of brain activity, machine learning classification and brain network analysis provides new tools for combating cognitive decline and brain aging in older adults. We optimistically conclude that NF, combined with new neuro-markers (event-related potentials and connectivity) and traditional features, promises to provide new hope for brain and CT in the growing older population. PMID:28348527

Halogenated Natural Products in Dolphins: Brain-Blubber Distribution and Comparison with Halogenated Flame Retardants.

PubMed

Barón, E; Hauler, C; Gallistl, C; Giménez, J; Gauffier, P; Castillo, J J; Fernández-Maldonado, C; de Stephanis, R; Vetter, W; Eljarrat, E; Barceló, D

2015-08-04

Halogenated natural products (MHC-1, TriBHD, TetraBHD, MeO-PBDEs, Q1, and related PMBPs) and halogenated flame retardants (PBDEs, HBB, Dec 602, Dec 603, and DP) in blubber and brain are reported from five Alboran Sea delphinids (Spain). Both HNPs and HFRs were detected in brain, implying that they are able to surpass the blood-brain barrier and reach the brain, which represents a new finding for some compounds, such as Q1 and PMBPs, MHC-1, TriBHD, TetraBHD, or Dec 603. Moreover, some compounds (TetraBHD, BDE-153, or HBB) presented higher levels in brain than in blubber. This study evidence the high concentrations of HNPs in the marine environment, especially in top predators. It shows the importance of further monitoring these natural compounds and evaluating their potential toxicity, when most studies focus on anthropogenic compounds only. While no bioaccumulation was found for ∑HNPs, ∑HFRs increased significantly with body size for both common and striped dolphins. Studies evaluating BBB permeation mechanisms of these compounds together with their potential neurotoxic effects in dolphins are recommended.

Habit formation.

PubMed

Smith, Kyle S; Graybiel, Ann M

2016-03-01

Habits, both good ones and bad ones, are pervasive in animal behavior. Important frameworks have been developed to understand habits through psychological and neurobiological studies. This work has given us a rich understanding of brain networks that promote habits, and has also helped us to understand what constitutes a habitual behavior as opposed to a behavior that is more flexible and prospective. Mounting evidence from studies using neural recording methods suggests that habit formation is not a simple process. We review this evidence and take the position that habits could be sculpted from multiple dissociable changes in neural activity. These changes occur across multiple brain regions and even within single brain regions. This strategy of classifying components of a habit based on different brain signals provides a potentially useful new way to conceive of disorders that involve overly fixed behaviors as arising from different potential dysfunctions within the brain's habit network.

Habit formation

PubMed Central

Smith, Kyle S.; Graybiel, Ann M.

2016-01-01

Habits, both good ones and bad ones, are pervasive in animal behavior. Important frameworks have been developed to understand habits through psychological and neurobiological studies. This work has given us a rich understanding of brain networks that promote habits, and has also helped us to understand what constitutes a habitual behavior as opposed to a behavior that is more flexible and prospective. Mounting evidence from studies using neural recording methods suggests that habit formation is not a simple process. We review this evidence and take the position that habits could be sculpted from multiple dissociable changes in neural activity. These changes occur across multiple brain regions and even within single brain regions. This strategy of classifying components of a habit based on different brain signals provides a potentially useful new way to conceive of disorders that involve overly fixed behaviors as arising from different potential dysfunctions within the brain's habit network. PMID:27069378

The Potential of Stem Cells in Treatment of Traumatic Brain Injury.

PubMed

Weston, Nicole M; Sun, Dong

2018-01-25

Traumatic brain injury (TBI) is a global public health concern, with limited treatment options available. Despite improving survival rate after TBI, treatment is lacking for brain functional recovery and structural repair in clinic. Recent studies have suggested that the mature brain harbors neural stem cells which have regenerative capacity following brain insults. Much progress has been made in preclinical TBI model studies in understanding the behaviors, functions, and regulatory mechanisms of neural stem cells in the injured brain. Different strategies targeting these cell population have been assessed in TBI models. In parallel, cell transplantation strategy using a wide range of stem cells has been explored for TBI treatment in pre-clinical studies and some in clinical trials. This review summarized strategies which have been explored to enhance endogenous neural stem cell-mediated regeneration and recent development in cell transplantation studies for post-TBI brain repair. Thus far, neural regeneration through neural stem cells either by modulating endogenous neural stem cells or by stem cell transplantation has attracted much attention. It is highly speculated that targeting neural stem cells could be a potential strategy to repair and regenerate the injured brain. Neuroprotection and neuroregeneration are major aspects for TBI therapeutic development. With technique advancement, it is hoped that stem cell-based therapy targeting neuroregeneration will be able to translate to clinic in not so far future.

Relationships between the resting-state network and the P3: Evidence from a scalp EEG study

NASA Astrophysics Data System (ADS)

Li, Fali; Liu, Tiejun; Wang, Fei; Li, He; Gong, Diankun; Zhang, Rui; Jiang, Yi; Tian, Yin; Guo, Daqing; Yao, Dezhong; Xu, Peng

2015-10-01

The P3 is an important event-related potential that can be used to identify neural activity related to the cognitive processes of the human brain. However, the relationships, especially the functional correlations, between resting-state brain activity and the P3 have not been well established. In this study, we investigated the relationships between P3 properties (i.e., amplitude and latency) and resting-state brain networks. The results indicated that P3 amplitude was significantly correlated with resting-state network topology, and in general, larger P3 amplitudes could be evoked when the resting-state brain network was more efficient. However, no significant relationships were found for the corresponding P3 latency. Additionally, the long-range connections between the prefrontal/frontal and parietal/occipital brain regions, which represent the synchronous activity of these areas, were functionally related to the P3 parameters, especially P3 amplitude. The findings of the current study may help us better understand inter-subject variation in the P3, which may be instructive for clinical diagnosis, cognitive neuroscience studies, and potential subject selection for brain-computer interface applications.

Dietary Tocotrienol/γ-Cyclodextrin Complex Increases Mitochondrial Membrane Potential and ATP Concentrations in the Brains of Aged Mice

PubMed Central

Schloesser, Anke; Esatbeyoglu, Tuba; Piegholdt, Stefanie; Dose, Janina; Ikuta, Naoko; Okamoto, Hinako; Ishida, Yoshiyuki; Terao, Keiji; Matsugo, Seiichi; Rimbach, Gerald

2015-01-01

Brain aging is accompanied by a decrease in mitochondrial function. In vitro studies suggest that tocotrienols, including γ- and δ-tocotrienol (T3), may exhibit neuroprotective properties. However, little is known about the effect of dietary T3 on mitochondrial function in vivo. In this study, we monitored the effect of a dietary T3/γ-cyclodextrin complex (T3CD) on mitochondrial membrane potential and ATP levels in the brain of 21-month-old mice. Mice were fed either a control diet or a diet enriched with T3CD providing 100 mg T3 per kg diet for 6 months. Dietary T3CD significantly increased mitochondrial membrane potential and ATP levels compared to those of controls. The increase in MMP and ATP due to dietary T3CD was accompanied by an increase in the protein levels of the mitochondrial transcription factor A (TFAM). Furthermore, dietary T3CD slightly increased the mRNA levels of superoxide dismutase, γ-glutamyl cysteinyl synthetase, and heme oxygenase 1 in the brain. Overall, the present data suggest that T3CD increases TFAM, mitochondrial membrane potential, and ATP synthesis in the brains of aged mice. PMID:26301044

Use of the Stockwell Transform in the Detection of P300 Evoked Potentials with Low-Cost Brain Sensors.

PubMed

Pérez-Vidal, Alan F; Garcia-Beltran, Carlos D; Martínez-Sibaja, Albino; Posada-Gómez, Rubén

2018-05-09

The evoked potential is a neuronal activity that originates when a stimulus is presented. To achieve its detection, various techniques of brain signal processing can be used. One of the most studied evoked potentials is the P300 brain wave, which usually appears between 300 and 500 ms after the stimulus. Currently, the detection of P300 evoked potentials is of great importance due to its unique properties that allow the development of applications such as spellers, lie detectors, and diagnosis of psychiatric disorders. The present study was developed to demonstrate the usefulness of the Stockwell transform in the process of identifying P300 evoked potentials using a low-cost electroencephalography (EEG) device with only two brain sensors. The acquisition of signals was carried out using the Emotiv EPOC ® device—a wireless EEG headset. In the feature extraction, the Stockwell transform was used to obtain time-frequency information. The algorithms of linear discriminant analysis and a support vector machine were used in the classification process. The experiments were carried out with 10 participants; men with an average age of 25.3 years in good health. In general, a good performance (75⁻92%) was obtained in identifying P300 evoked potentials.

Nose-to-Brain Delivery of Peptide Drugs Enhanced by Coadministration of Cell-penetrating Peptides: Therapeutic Potential for Dementia.

PubMed

Kamei, Noriyasu

2017-01-01

Recent reports suggest that peptide drugs such as insulin have the potential to serve as therapeutics in neurodegenerative diseases such as Alzheimer's disease. However, the transport of these drugs to the therapeutic target, the brain, is significantly hindered by the blood-brain barrier (BBB). Intranasal administration appears to be an ideal solution for drug delivery to the brain, bypassing the BBB, however the entry of peptide drugs into neuronal and epithelial cells in the olfactory mucosa remains low. In this study, we therefore examined whether intranasal coadministration of cell-penetrating peptides (CPPs) could improve nose-to-brain drug transport. In both mice and rats, we found that direct transport of insulin into the brain was significantly facilitated when coadministered with amphipathic CPP penetratin, and eventually insulin reached the deeper regions of the brain such as the hippocampus. In the mouse line senescence-accelerated mouse prone-8 (SAMP8), spatial learning tests demonstrated that long-term intranasal coadministration of insulin with penetratin improved mild memory loss in the early stages of dementia. In contrast, the severe cognitive dysfunction in the aged SAMP8 mice was preserved despite intranasal coadministration of insulin with penetratin. The immunohistological examination of the hippocampus suggested that enhanced nose-to-brain delivery of insulin had a partial neuroprotective effect but unexpectedly increased amyloid β plaque deposition. In conclusion, intranasal coadministration of insulin with CPPs has the potential to serve as a therapeutic for mild cognitive dysfunction. To identify suitable pharmacotherapy for dementia with severe pathology, further studies of nose-to-brain delivery of molecularly appropriate biopharmaceuticals are necessary.

The MOBI-Kids Study Protocol: Challenges in Assessing Childhood and Adolescent Exposure to Electromagnetic Fields from Wireless Telecommunication Technologies and Possible Association with Brain Tumor Risk

PubMed Central

Sadetzki, Siegal; Langer, Chelsea Eastman; Bruchim, Revital; Kundi, Michael; Merletti, Franco; Vermeulen, Roel; Kromhout, Hans; Lee, Ae-Kyoung; Maslanyj, Myron; Sim, Malcolm R.; Taki, Masao; Wiart, Joe; Armstrong, Bruce; Milne, Elizabeth; Benke, Geza; Schattner, Rosa; Hutter, Hans-Peter; Woehrer, Adelheid; Krewski, Daniel; Mohipp, Charmaine; Momoli, Franco; Ritvo, Paul; Spinelli, John; Lacour, Brigitte; Delmas, Dominique; Remen, Thomas; Radon, Katja; Weinmann, Tobias; Klostermann, Swaantje; Heinrich, Sabine; Petridou, Eleni; Bouka, Evdoxia; Panagopoulou, Paraskevi; Dikshit, Rajesh; Nagrani, Rajini; Even-Nir, Hadas; Chetrit, Angela; Maule, Milena; Migliore, Enrica; Filippini, Graziella; Miligi, Lucia; Mattioli, Stefano; Yamaguchi, Naohito; Kojimahara, Noriko; Ha, Mina; Choi, Kyung-Hwa; Mannetje, Andrea ’t; Eng, Amanda; Woodward, Alistair; Carretero, Gema; Alguacil, Juan; Aragones, Nuria; Suare-Varela, Maria Morales; Goedhart, Geertje; Schouten-van Meeteren, A. Antoinette Y. N.; Reedijk, A. Ardine M. J.; Cardis, Elisabeth

2014-01-01

The rapid increase in mobile phone use in young people has generated concern about possible health effects of exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF). MOBI-Kids, a multinational case–control study, investigates the potential effects of childhood and adolescent exposure to EMF from mobile communications technologies on brain tumor risk in 14 countries. The study, which aims to include approximately 1,000 brain tumor cases aged 10–24 years and two individually matched controls for each case, follows a common protocol and builds upon the methodological experience of the INTERPHONE study. The design and conduct of a study on EMF exposure and brain tumor risk in young people in a large number of countries is complex and poses methodological challenges. This manuscript discusses the design of MOBI-Kids and describes the challenges and approaches chosen to address them, including: (1) the choice of controls operated for suspected appendicitis, to reduce potential selection bias related to low response rates among population controls; (2) investigating a young study population spanning a relatively wide age range; (3) conducting a large, multinational epidemiological study, while adhering to increasingly stricter ethics requirements; (4) investigating a rare and potentially fatal disease; and (5) assessing exposure to EMF from communication technologies. Our experience in thus far developing and implementing the study protocol indicates that MOBI-Kids is feasible and will generate results that will contribute to the understanding of potential brain tumor risks associated with use of mobile phones and other wireless communications technologies among young people. PMID:25295243

The MOBI-Kids Study Protocol: Challenges in Assessing Childhood and Adolescent Exposure to Electromagnetic Fields from Wireless Telecommunication Technologies and Possible Association with Brain Tumor Risk.

PubMed

Sadetzki, Siegal; Langer, Chelsea Eastman; Bruchim, Revital; Kundi, Michael; Merletti, Franco; Vermeulen, Roel; Kromhout, Hans; Lee, Ae-Kyoung; Maslanyj, Myron; Sim, Malcolm R; Taki, Masao; Wiart, Joe; Armstrong, Bruce; Milne, Elizabeth; Benke, Geza; Schattner, Rosa; Hutter, Hans-Peter; Woehrer, Adelheid; Krewski, Daniel; Mohipp, Charmaine; Momoli, Franco; Ritvo, Paul; Spinelli, John; Lacour, Brigitte; Delmas, Dominique; Remen, Thomas; Radon, Katja; Weinmann, Tobias; Klostermann, Swaantje; Heinrich, Sabine; Petridou, Eleni; Bouka, Evdoxia; Panagopoulou, Paraskevi; Dikshit, Rajesh; Nagrani, Rajini; Even-Nir, Hadas; Chetrit, Angela; Maule, Milena; Migliore, Enrica; Filippini, Graziella; Miligi, Lucia; Mattioli, Stefano; Yamaguchi, Naohito; Kojimahara, Noriko; Ha, Mina; Choi, Kyung-Hwa; Mannetje, Andrea 't; Eng, Amanda; Woodward, Alistair; Carretero, Gema; Alguacil, Juan; Aragones, Nuria; Suare-Varela, Maria Morales; Goedhart, Geertje; Schouten-van Meeteren, A Antoinette Y N; Reedijk, A Ardine M J; Cardis, Elisabeth

2014-01-01

The rapid increase in mobile phone use in young people has generated concern about possible health effects of exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF). MOBI-Kids, a multinational case-control study, investigates the potential effects of childhood and adolescent exposure to EMF from mobile communications technologies on brain tumor risk in 14 countries. The study, which aims to include approximately 1,000 brain tumor cases aged 10-24 years and two individually matched controls for each case, follows a common protocol and builds upon the methodological experience of the INTERPHONE study. The design and conduct of a study on EMF exposure and brain tumor risk in young people in a large number of countries is complex and poses methodological challenges. This manuscript discusses the design of MOBI-Kids and describes the challenges and approaches chosen to address them, including: (1) the choice of controls operated for suspected appendicitis, to reduce potential selection bias related to low response rates among population controls; (2) investigating a young study population spanning a relatively wide age range; (3) conducting a large, multinational epidemiological study, while adhering to increasingly stricter ethics requirements; (4) investigating a rare and potentially fatal disease; and (5) assessing exposure to EMF from communication technologies. Our experience in thus far developing and implementing the study protocol indicates that MOBI-Kids is feasible and will generate results that will contribute to the understanding of potential brain tumor risks associated with use of mobile phones and other wireless communications technologies among young people.

Transferrin-modified liposome promotes α-mangostin to penetrate the blood-brain barrier.

PubMed

Chen, Zhi-Lan; Huang, Man; Wang, Xia-Rong; Fu, Jun; Han, Min; Shen, You-Qing; Xia, Zheng; Gao, Jian-Qing

2016-02-01

α-Mangostin (α-M) is a polyphenolic xanthone that protects and improves the survival of cerebral cortical neurons against Aβ oligomer-induced toxicity in rats. α-M is a potential candidate as a treatment for Alzheimer's disease (AD). However, the efficacy was limited by the poor penetration of the drug through the blood-brain barrier (BBB). In this study, we modified the α-M liposome with transferrin (Tf) and investigated the intracellular distribution of liposomes in bEnd3 cells. In addition, the transport of α-M across the BBB in the Tf(α-M) liposome group was examined. In vitro studies demonstrated that the Tf(α-M) liposome could cross the BBB in the form of an integrated liposome. Results of the in vivo studies on the α-M distribution in the brain demonstrated that the Tf(α-M) liposome improved the brain delivery of α-M. These results indicated that the Tf liposome is a potential carrier of α-M against AD. The use of α-Mangostin (α-M) as a potential agent to treat Alzheimer's disease (AD) has been reported. However, its use is limited by the poor penetration through the blood brain barrier. The delivery of this agent by transferrin-modified liposomes was investigated by the authors in this study. The positive results could point to a better drug delivery system for brain targeting. Copyright © 2015 Elsevier Inc. All rights reserved.

Metformin treatment after the hypoxia-ischemia attenuates brain injury in newborn rats

PubMed Central

Fang, Mingchu; Jiang, Huai; Ye, Lixia; Cai, Chenchen; Hu, Yingying; Pan, Shulin; Li, Peijun; Xiao, Jian; Lin, Zhenlang

2017-01-01

Neonatal hypoxic-ischemic (HI) brain injury is a devastating disease that often leads to death and detrimental neurological deficits. The present study was designed to evaluate the ability of metformin to provide neuroprotection in a model of neonatal hypoxic-ischemic brain injury and to study the associated molecular mechanisms behind these protective effects. Here, we found that metformin treatment remarkably attenuated brain infarct volumes and brain edema at 24 h after HI injury, and the neuroprotection of metformin was associated with inhibition of neuronal apoptosis, suppression of the neuroinflammation and amelioration of the blood brain barrier breakdown. Additionally, metformin treatment conferred long-term protective against brain damage at 7 d after HI injury. Our study indicates that metformin treatment protects against neonatal hypoxic-ischemic brain injury and thus has potential as a therapy for this disease. PMID:29088867

Multiple Brain Markers are Linked to Age-Related Variation in Cognition

PubMed Central

Hedden, Trey; Schultz, Aaron P.; Rieckmann, Anna; Mormino, Elizabeth C.; Johnson, Keith A.; Sperling, Reisa A.; Buckner, Randy L.

2016-01-01

Age-related alterations in brain structure and function have been challenging to link to cognition due to potential overlapping influences of multiple neurobiological cascades. We examined multiple brain markers associated with age-related variation in cognition. Clinically normal older humans aged 65–90 from the Harvard Aging Brain Study (N = 186) were characterized on a priori magnetic resonance imaging markers of gray matter thickness and volume, white matter hyperintensities, fractional anisotropy (FA), resting-state functional connectivity, positron emission tomography markers of glucose metabolism and amyloid burden, and cognitive factors of processing speed, executive function, and episodic memory. Partial correlation and mediation analyses estimated age-related variance in cognition shared with individual brain markers and unique to each marker. The largest relationships linked FA and striatum volume to processing speed and executive function, and hippocampal volume to episodic memory. Of the age-related variance in cognition, 70–80% was accounted for by combining all brain markers (but only ∼20% of total variance). Age had significant indirect effects on cognition via brain markers, with significant markers varying across cognitive domains. These results suggest that most age-related variation in cognition is shared among multiple brain markers, but potential specificity between some brain markers and cognitive domains motivates additional study of age-related markers of neural health. PMID:25316342

Effects of DTNBP1 Genotype on Brain Development in Children

ERIC Educational Resources Information Center

Tognin, Stefania; Viding, Essi; McCrory, Eamon J.; Taylor, Lauren; O'Donovan, Michael C.; McGuire, Philip; Mechelli, Andrea

2011-01-01

Background: Schizophrenia is a neurodevelopmental disorder, and risk genes are thought to act through disruption of brain development. Several genetic studies have identified dystrobrevin-binding protein 1 (DTNBP1, also known as dysbindin) as a potential susceptibility gene for schizophrenia, but its impact on brain development is poorly…

Adolescent Brain Development and Implications for Classroom Management

ERIC Educational Resources Information Center

Mears, Derrick

2012-01-01

Studies using Magnetic Resonance Imaging (MRI) to observe the adolescent brain have shown that during adolescence multiple changes are occurring. This can provide a potential explanation for the sporadic and seemingly unpredictable behaviors that appear. It is believed that the brain of an adolescent goes through a profound neurological…

Relationship between concentrations of lutein and StARD3 among pediatric and geriatric human brain tissue

USDA-ARS?s Scientific Manuscript database

Lutein, a dietary carotenoid, selectively accumulates in human retina and brain. While many epidemiological studies show evidence of a relationship between lutein status and cognitive health, lutein's selective uptake in human brain tissue and its potential function in early neural development and c...

Cognitive Remediation: Potential Novel Brain-Based Treatment for Bipolar Disorder in Children and Adolescents

PubMed Central

Dickstein, Daniel P.; Cushman, Grace K.; Kim, Kerri L.; Weissman, Alexandra B.; Wegbreit, Ezra

2015-01-01

Bipolar disorder (BD) is among the most impairing psychiatric disorders affecting children and adolescents, despite our best psychopharmacological and psychotherapeutic treatments. Cognitive remediation, defined as a behavioral intervention designed to improve cognitive functions so as to reduce psychiatric illness, is an emerging brain-based treatment approach that has thus far not been studied in pediatric BD. The present article reviews the basic principles of cognitive remediation, describes what is known about cognitive remediation in psychiatric disorders, and delineates potential brain/behavior alterations implicated in pediatric BD that might be targets for cognitive remediation. Emerging data shows that cognitive remediation may be useful in children and adults with schizophrenia, ADHD, and anxiety disorders, and in adults with BD. Potential targets for cognitive remediation in pediatric BD include face processing, response inhibition, frustration, and cognitive flexibility. Further study is warranted to determine if cognitive remediation for these targets, or others, may serve as a novel, brain-based treatment for pediatric BD. PMID:26135596

Potential roles of hyperbaric oxygenation in the treatments of brain tumors.

PubMed

Kohshi, Kiyotaka; Beppu, Takaaki; Tanaka, Katsuyuki; Ogawa, Kazuhiko; Inoue, Osamu; Kukita, Ichiro; Clarke, Richard E

2013-01-01

Over the past 50 years hyperbaric oxygen (HBO2) therapy has been used in a wide variety of medical conditions, and one of them is cancer. Many clinical studies have been conducted to evaluate potential therapeutic effects of HBO2 as a part of cancer treatment. This review briefly summaries the potential role of HBO2 therapy in the treatment of malignant tumors and radiation injury of the brain. HBO2 therapy is used for the enhancement of radiosensitivity in the treatment of some cancers, including malignant brain tumors. Radiotherapy within 15 minutes following HBO2 exposure, a relatively new treatment regimen, has been studied at several institutes and has demonstrated promising clinical results for malignant gliomas of the brain. HBO2 therapy also increases sensitivity to some antineoplastic agents; non-randomized clinical trials using carboplatin-based chemotherapy combined with HBO2 show a significant advantage in survival for recurrent malignant gliomas. The possibilities of combining HBO2 therapy with radiotherapy and/or chemotherapy to overcome newly diagnosed and recurrent malignant gliomas deserve extensive clinical trials. HBO2 therapy also shows promising potential for the treatment and/or prevention of radiation injury of the brain after stereotactic radiosurgery for brain lesions. The possibilities with HBO2 to enhance the therapeutic effect of irradiation per se, and to even increase the radiation dose if there are ways to combat the side effects, should boost new scientific interest into the whole field of oncology looking for new armamentaria to fight cancer.

Atypical Brain Responses to Reward Cues in Autism as Revealed by Event-Related Potentials

ERIC Educational Resources Information Center

Kohls, Gregor; Peltzer, Judith; Schulte-Ruther, Martin; Kamp-Becker, Inge; Remschmidt, Helmut; Herpertz-Dahlmann, Beate; Konrad, Kerstin

2011-01-01

Social motivation deficit theories suggest that children with autism do not properly anticipate and appreciate the pleasure of social stimuli. In this study, we investigated event-related brain potentials evoked by cues that triggered social versus monetary reward anticipation in children with autism. Children with autism showed attenuated P3…

The FMRP regulon: from targets to disease convergence

PubMed Central

Fernández, Esperanza; Rajan, Nicholas; Bagni, Claudia

2013-01-01

The fragile X mental retardation protein (FMRP) is an RNA-binding protein that regulates mRNA metabolism. FMRP has been largely studied in the brain, where the absence of this protein leads to fragile X syndrome, the most frequent form of inherited intellectual disability. Since the identification of the FMRP gene in 1991, many studies have primarily focused on understanding the function/s of this protein. Hundreds of potential FMRP mRNA targets and several interacting proteins have been identified. Here, we report the identification of FMRP mRNA targets in the mammalian brain that support the key role of this protein during brain development and in regulating synaptic plasticity. We compared the genes from databases and genome-wide association studies with the brain FMRP transcriptome, and identified several FMRP mRNA targets associated with autism spectrum disorders, mood disorders and schizophrenia, showing a potential common pathway/s for these apparently different disorders. PMID:24167470

Approximate reasoning by pairwise comparisons. "Topodynamics of metastable brains" by Arturo Tozzi, et al.

NASA Astrophysics Data System (ADS)

Kakiashvili, Tamar; Koczkodaj, Waldemar W.; Magnot, Jean-Pierre

2017-07-01

The innovative approach in [1], ;Topodynamics of Metastable Brains; by Arturo Tozzi, James Peters, Andrew Fingelkurts, Alexander Fingelkurts, and Pedro Marijuan has a high potential of becoming a paradigm shift in the brain research. It seems that this study has successfully explored the possibility of applying a celebrated Borsuk-Ulam theorem to the operational architectonics of the fundamental brain-mind processes.

Independent component analysis of EEG dipole source localization in resting and action state of brain

NASA Astrophysics Data System (ADS)

Almurshedi, Ahmed; Ismail, Abd Khamim

2015-04-01

EEG source localization was studied in order to determine the location of the brain sources that are responsible for the measured potentials at the scalp electrodes using EEGLAB with Independent Component Analysis (ICA) algorithm. Neuron source locations are responsible in generating current dipoles in different states of brain through the measured potentials. The current dipole sources localization are measured by fitting an equivalent current dipole model using a non-linear optimization technique with the implementation of standardized boundary element head model. To fit dipole models to ICA components in an EEGLAB dataset, ICA decomposition is performed and appropriate components to be fitted are selected. The topographical scalp distributions of delta, theta, alpha, and beta power spectrum and cross coherence of EEG signals are observed. In close eyes condition it shows that during resting and action states of brain, alpha band was activated from occipital (O1, O2) and partial (P3, P4) area. Therefore, parieto-occipital area of brain are active in both resting and action state of brain. However cross coherence tells that there is more coherence between right and left hemisphere in action state of brain than that in the resting state. The preliminary result indicates that these potentials arise from the same generators in the brain.

Agent based modeling of the effects of potential treatments over the blood-brain barrier in multiple sclerosis.

PubMed

Pennisi, Marzio; Russo, Giulia; Motta, Santo; Pappalardo, Francesco

2015-12-01

Multiple sclerosis is a disease of the central nervous system that involves the destruction of the insulating sheath of axons, causing severe disabilities. Since the etiology of the disease is not yet fully understood, the use of novel techniques that may help to understand the disease, to suggest potential therapies and to test the effects of candidate treatments is highly advisable. To this end we developed an agent based model that demonstrated its ability to reproduce the typical oscillatory behavior observed in the most common form of multiple sclerosis, relapsing-remitting multiple sclerosis. The model has then been used to test the potential beneficial effects of vitamin D over the disease. Many scientific studies underlined the importance of the blood-brain barrier and of the mechanisms that influence its permeability on the development of the disease. In the present paper we further extend our previously developed model with a mechanism that mimics the blood-brain barrier behavior. The goal of our work is to suggest the best strategies to follow for developing new potential treatments that intervene in the blood-brain barrier. Results suggest that the best treatments should potentially prevent the opening of the blood-brain barrier, as treatments that help in recovering the blood-brain barrier functionality could be less effective. Copyright © 2015 Elsevier B.V. All rights reserved.

Inhibition of type I insulin-like growth factor receptor signaling attenuates the development of breast cancer brain metastasis.

PubMed

Saldana, Sandra M; Lee, Heng-Huan; Lowery, Frank J; Khotskaya, Yekaterina B; Xia, Weiya; Zhang, Chenyu; Chang, Shih-Shin; Chou, Chao-Kai; Steeg, Patricia S; Yu, Dihua; Hung, Mien-Chie

2013-01-01

Brain metastasis is a common cause of mortality in cancer patients, yet potential therapeutic targets remain largely unknown. The type I insulin-like growth factor receptor (IGF-IR) is known to play a role in the progression of breast cancer and is currently being investigated in the clinical setting for various types of cancer. The present study demonstrates that IGF-IR is constitutively autophosphorylated in brain-seeking breast cancer sublines. Knockdown of IGF-IR results in a decrease of phospho-AKT and phospho-p70s6k, as well as decreased migration and invasion of MDA-MB-231Br brain-seeking cells. In addition, transient ablation of IGFBP3, which is overexpressed in brain-seeking cells, blocks IGF-IR activation. Using an in vivo experimental brain metastasis model, we show that IGF-IR knockdown brain-seeking cells have reduced potential to establish brain metastases. Finally, we demonstrate that the malignancy of brain-seeking cells is attenuated by pharmacological inhibition with picropodophyllin, an IGF-IR-specific tyrosine kinase inhibitor. Together, our data suggest that the IGF-IR is an important mediator of brain metastasis and its ablation delays the onset of brain metastases in our model system.

Deconstructing multivariate decoding for the study of brain function.

PubMed

Hebart, Martin N; Baker, Chris I

2017-08-04

Multivariate decoding methods were developed originally as tools to enable accurate predictions in real-world applications. The realization that these methods can also be employed to study brain function has led to their widespread adoption in the neurosciences. However, prior to the rise of multivariate decoding, the study of brain function was firmly embedded in a statistical philosophy grounded on univariate methods of data analysis. In this way, multivariate decoding for brain interpretation grew out of two established frameworks: multivariate decoding for predictions in real-world applications, and classical univariate analysis based on the study and interpretation of brain activation. We argue that this led to two confusions, one reflecting a mixture of multivariate decoding for prediction or interpretation, and the other a mixture of the conceptual and statistical philosophies underlying multivariate decoding and classical univariate analysis. Here we attempt to systematically disambiguate multivariate decoding for the study of brain function from the frameworks it grew out of. After elaborating these confusions and their consequences, we describe six, often unappreciated, differences between classical univariate analysis and multivariate decoding. We then focus on how the common interpretation of what is signal and noise changes in multivariate decoding. Finally, we use four examples to illustrate where these confusions may impact the interpretation of neuroimaging data. We conclude with a discussion of potential strategies to help resolve these confusions in interpreting multivariate decoding results, including the potential departure from multivariate decoding methods for the study of brain function. Copyright © 2017. Published by Elsevier Inc.

[Brainstem auditory evoked potentials in neurophysiological assessment of brain stem dysfunction in patients with atherostenosis of vertebral arteries].

PubMed

Maksimova, M Yu; Sermagambetova, Zh N; Skrylev, S I; Fedin, P A; Koshcheev, A Yu; Shchipakin, V L; Sinicyn, I A

To assess brain stem dysfunction in patients with hemodynamically significant stenosis of vertebral arteries (VA) using short latency brainstem auditory evoked potentials (BAEP). The study group included 50 patients (mean age 64±6 years) with hemodynamically significant extracranial VA stenosis. Patients with hemodynamically significant extracranial VA stenosis had BAEP abnormalities including the elongation of interpeak intervals I-V and peak V latency as well as the reduction of peak I amplitude. After transluminal balloon angioplasty with stenting of VA stenoses, there was a shortening of peak V latency compared to the preoperative period that reflected the improvement of brain stem conductive functions. Atherostenosis of vertebral arteries is characterized by the signs of brain stem dysfunction, predominantly in the pontomesencephal brain stem. After transluminal balloon angioplasty with stenting of VA, the improvement of brain stem conductive functions was observed.

The maternal brain and its plasticity in humans

PubMed Central

Kim, Pilyoung; Strathearn, Lane; Swain, James E.

2015-01-01

Early mother-infant relationships play important roles in infants’ optimal development. New mothers undergo neurobiological changes that support developing mother-infant relationships regardless of great individual differences in those relationships. In this article, we review the neural plasticity in human mothers’ brains based on functional magnetic resonance imaging (fMRI) studies. First, we review the neural circuits that are involved in establishing and maintaining mother-infant relationships. Second, we discuss early postpartum factors (e.g., birth and feeding methods, hormones, and parental sensitivity) that are associated with individual differences in maternal brain neuroplasticity. Third, we discuss abnormal changes in the maternal brain related to psychopathology (i.e., postpartum depression, posttraumatic stress disorder, substance abuse) and potential brain remodeling associated with interventions. Last, we highlight potentially important future research directions to better understand normative changes in the maternal brain and risks for abnormal changes that may disrupt early mother-infant relationships. PMID:26268151

A review on potential neurotoxicity of titanium dioxide nanoparticles

NASA Astrophysics Data System (ADS)

Song, Bin; Liu, Jia; Feng, Xiaoli; Wei, Limin; Shao, Longquan

2015-08-01

As the rapid development of nanotechnology in the past three decades, titanium dioxide nanoparticles (TiO2 NPs), for their peculiar physicochemical properties, are widely applied in consumer products, food additives, cosmetics, drug carriers, and so on. However, little is known about their potential exposure and neurotoxic effects. Once NPs are unintentionally exposed to human beings, they could be absorbed, and then accumulated in the brain regions by passing through the blood-brain barrier (BBB) or through the nose-to-brain pathway, potentially leading to dysfunctions of central nerve system (CNS). Besides, NPs may affect the brain development of embryo by crossing the placental barrier. A few in vivo and in vitro researches have demonstrated that the morphology and function of neuronal or glial cells could be impaired by TiO2 NPs which might induce cell necrosis. Cellular components, such as mitochondrial, lysosome, and cytoskeleton, could also be influenced as well. The recognition ability, spatial memory, and learning ability of TiO2 NPs-treated rodents were significantly impaired, which meant that accumulation of TiO2 NPs in the brain could lead to neurodegeneration. However, conclusions obtained from those studies were not consistent with each other as researchers may choose different experimental parameters, including administration ways, dosage, size, and crystal structure of TiO2 NPs. Therefore, in order to fully understand the potential risks of TiO2 NPs to brain health, figure out research areas where further studies are required, and improve its bio-safety for applications in the near future, how TiO2 NPs interact with the brain is investigated in this review by summarizing the current researches on neurotoxicity induced by TiO2 NPs.

Enriching the Brain: How to Maximize Every Learner's Potential

ERIC Educational Resources Information Center

Jensen, Eric

2006-01-01

Eric Jensen, a leading expert in the translation of brain research into education, argues that students' achievement capacity is greatly underappreciated. Drawing from a wide range of neuroscience research as well as related studies, the author reveals that the human brain is far more dynamic and malleable than earlier believed. He offers a…

Perivascular Spaces--MRI Marker of Inflammatory Activity in the Brain?

ERIC Educational Resources Information Center

Wuerfel, Jens; Haertle, Mareile; Waiczies, Helmar; Tysiak, Eva; Bechmann, Ingo; Wernecke, Klaus D.; Zipp, Frauke; Paul, Friedemann

2008-01-01

The Virchow-Robin spaces (VRS), perivascular compartments surrounding small blood vessels as they penetrate the brain parenchyma, are increasingly recognized for their role in leucocyte trafficking as well as for their potential to modulate immune responses. In the present study, we investigated VRS numbers and volumes in different brain regions…

Brain-Science Based Cohort Studies

ERIC Educational Resources Information Center

Koizumi, Hideaki

2011-01-01

This article describes a number of human cohort studies based on the concept of brain-science and education. These studies assess the potential effects of new technologies on babies, children and adolescents, and test hypotheses drawn from animal and genetic case studies to see if they apply to people. A flood of information, virtual media,…

Facebook as communication support for persons with potential mild acquired cognitive impairment: A content and social network analysis study.

PubMed

Eghdam, Aboozar; Hamidi, Ulrika; Bartfai, Aniko; Koch, Sabine

2018-01-01

Social media has the potential to increase social participation and support for the well-being of individuals with chronic medical conditions. To date, Facebook is the most popular social medium for different types of communication. However, there is a lack of knowledge about the potential use of Facebook as a means of communication for persons with potential Mild Acquired Cognitive Impairment (MACI), a non-progressive mild cognitive impairment after an acquired brain injury. The aim of this study was to explore how persons with potential MACI, specifically persons with perceived brain fatigue after brain injury, communicate through Facebook, to classify the content of the communication and to visualize the frequency and types of interactions. A social network analysis of the interactions between members' and a qualitative content analysis of a whole year's communication of a public Facebook group for Swedish speaking persons (1310 members) with perceived brain fatigue after an illness or injury to the brain were performed. The results showed how members use social media technology and Facebook as a means for communication and support for their condition. Individual group members showed very different patterns of communication and interactions. However, for the group as a whole, the most frequent topics in their communication were related to informational support and banter in posts, and socialization in comments. The findings also showed that the majority of members only communicated with few other members and had few direct communications. The most used communication feature of Facebook was likes in form of "thumbs-up". This study indicated that social media and in this case Facebook is used for communication and social support by persons with potential MACI, and revealed that their communication behavior is similar to the healthy population. Further studies relating specific cognitive problems of the participants to the use of social media would provide more reliable results for this specific group.

Facebook as communication support for persons with potential mild acquired cognitive impairment: A content and social network analysis study

PubMed Central

Hamidi, Ulrika; Bartfai, Aniko; Koch, Sabine

2018-01-01

Introduction Social media has the potential to increase social participation and support for the well-being of individuals with chronic medical conditions. To date, Facebook is the most popular social medium for different types of communication. However, there is a lack of knowledge about the potential use of Facebook as a means of communication for persons with potential Mild Acquired Cognitive Impairment (MACI), a non-progressive mild cognitive impairment after an acquired brain injury. The aim of this study was to explore how persons with potential MACI, specifically persons with perceived brain fatigue after brain injury, communicate through Facebook, to classify the content of the communication and to visualize the frequency and types of interactions. Methods and materials A social network analysis of the interactions between members’ and a qualitative content analysis of a whole year’s communication of a public Facebook group for Swedish speaking persons (1310 members) with perceived brain fatigue after an illness or injury to the brain were performed. Results The results showed how members use social media technology and Facebook as a means for communication and support for their condition. Individual group members showed very different patterns of communication and interactions. However, for the group as a whole, the most frequent topics in their communication were related to informational support and banter in posts, and socialization in comments. The findings also showed that the majority of members only communicated with few other members and had few direct communications. The most used communication feature of Facebook was likes in form of “thumbs-up”. Conclusions This study indicated that social media and in this case Facebook is used for communication and social support by persons with potential MACI, and revealed that their communication behavior is similar to the healthy population. Further studies relating specific cognitive problems of the participants to the use of social media would provide more reliable results for this specific group. PMID:29377930

Teaching About "Brain and Learning" in High School Biology Classes: Effects on Teachers' Knowledge and Students' Theory of Intelligence.

PubMed

Dekker, Sanne; Jolles, Jelle

2015-01-01

This study evaluated a new teaching module about "Brain and Learning" using a controlled design. The module was implemented in high school biology classes and comprised three lessons: (1) brain processes underlying learning; (2) neuropsychological development during adolescence; and (3) lifestyle factors that influence learning performance. Participants were 32 biology teachers who were interested in "Brain and Learning" and 1241 students in grades 8-9. Teachers' knowledge and students' beliefs about learning potential were examined using online questionnaires. Results indicated that before intervention, biology teachers were significantly less familiar with how the brain functions and develops than with its structure and with basic neuroscientific concepts (46 vs. 75% correct answers). After intervention, teachers' knowledge of "Brain and Learning" had significantly increased (64%), and more students believed that intelligence is malleable (incremental theory). This emphasizes the potential value of a short teaching module, both for improving biology teachers' insights into "Brain and Learning," and for changing students' beliefs about intelligence.

Can nutraceuticals prevent Alzheimer's disease? Potential therapeutic role of a formulation containing shilajit and complex B vitamins.

PubMed

Carrasco-Gallardo, Carlos; Farías, Gonzalo A; Fuentes, Patricio; Crespo, Fernando; Maccioni, Ricardo B

2012-11-01

Alzheimer's disease (AD) is a brain disorder displaying a prevalence and impact in constant expansion. This expansive and epidemic behavior is concerning medical and public opinion while focusing efforts on its prevention and treatment. One important strategy to prevent this brain impairment is based on dietary changes and nutritional supplements, functional foods and nutraceuticals. In this review we discuss the potential contributions of shilajit and complex B vitamins to AD prevention. We analyze the status of biological studies and present data of a clinical trial developed in patients with mild AD. Studies suggest that shilajit and its active principle fulvic acid, as well as a formula of shilajit with B complex vitamins, emerge as novel nutraceutical with potential uses against this brain disorder. Copyright © 2012 IMSS. Published by Elsevier Inc. All rights reserved.

Effects of emotional valence and three-dimensionality of visual stimuli on brain activation: an fMRI study.

PubMed

Dores, A R; Almeida, I; Barbosa, F; Castelo-Branco, M; Monteiro, L; Reis, M; de Sousa, L; Caldas, A Castro

2013-01-01

Examining changes in brain activation linked with emotion-inducing stimuli is essential to the study of emotions. Due to the ecological potential of techniques such as virtual reality (VR), inspection of whether brain activation in response to emotional stimuli can be modulated by the three-dimensional (3D) properties of the images is important. The current study sought to test whether the activation of brain areas involved in the emotional processing of scenarios of different valences can be modulated by 3D. Therefore, the focus was made on the interaction effect between emotion-inducing stimuli of different emotional valences (pleasant, unpleasant and neutral valences) and visualization types (2D, 3D). However, main effects were also analyzed. The effect of emotional valence and visualization types and their interaction were analyzed through a 3 × 2 repeated measures ANOVA. Post-hoc t-tests were performed under a ROI-analysis approach. The results show increased brain activation for the 3D affective-inducing stimuli in comparison with the same stimuli in 2D scenarios, mostly in cortical and subcortical regions that are related to emotional processing, in addition to visual processing regions. This study has the potential of clarify brain mechanisms involved in the processing of emotional stimuli (scenarios' valence) and their interaction with three-dimensionality.

Acute injection of drugs with low addictive potential (delta(9)-tetrahydrocannabinol, 3,4-methylenedioxymethamphetamine, lysergic acid diamide) causes a much higher c-fos expression in limbic brain areas than highly addicting drugs (cocaine and morphine).

PubMed

Erdtmann-Vourliotis, M; Mayer, P; Riechert, U; Höllt, V

1999-08-25

It is regarded as a common pharmacological property responsible for the addictive potential of drugs of abuse that they are able to activate brain areas involved in the sensation of pleasure, especially the nucleus accumbens. To investigate the connection between addictive potential and stimulation of critical brain areas in more detail, we studied c-fos accumulation in response to various addicting drugs in direct comparison. The substances were injected into drug-naive rats, and c-fos mRNA levels were measured throughout the brain by in situ hybridization. Cocaine in a high dose of 50 mg/kg yielded only a discrete c-fos expression in the medial and central striatum. Morphine (50 mg/kg) caused a weak c-fos synthesis in the lateral septum. THC (delta(9)-tetrahydrocannabinol), 25 mg/kg, induced c-fos mRNA again in the lateral septum and furthermore in large parts of the striatum including the nucleus accumbens. LSD (lysergic acid diamide), 1 mg/kg, elicited a similar c-fos expression pattern as THC, but there was additionally a very strong hybridization signal in the cerebral cortex, especially in the upper layers, and in the ventral part of the periaqueductal gray. The widest range of brain areas was activated by MDMA (3, 4-methylenedioxymethamphetamine, 'ecstasy'), 6 mg/kg. In addition to the regions that responded to LSD, there was a very pronounced c-fos signal in the nucleus accumbens core and shell and in the mammillary nuclei. Taken together, our study revealed that the drugs with the highest addictive potential, cocaine and morphine, yielded a very low c-fos synthesis throughout the brain whereas the brain regions closely linked to pleasure (especially the nucleus accumbens) responded strongly to drugs with an apparently lower addictive potential (THC, LSD, MDMA).

Environmental Chemicals and Aging.

PubMed

Pearson, Brandon L; Ehninger, Dan

2017-03-01

Innovations in agriculture and medicine as well as industrial and domestic technologies are essential for the growing and aging global population. These advances generally require the use of novel natural or synthetic chemical agents with the potential to affect human health. Here, we attempt to highlight environmental chemicals and select drugs with the potential to exacerbate aging by directly affecting molecular aging cascades focusing particular attention on the brain. Finally, we call attention to some potential fruitful areas of research, particularly with advanced molecular profiling that could aid in prevention or mitigation of environmental chemical toxic influences in the periphery and the brain. We briefly summarize new research and highlight a recent study designed to prospectively identify agrochemicals with the potential to induce neurological diseases and place these discoveries into the already rich neurodegeneration and aging literature. Collectively, the research reviewed briefly here highlight chemicals with the true potential to accelerate aging, particularly in the brain, by eliciting elevated free radical stress and mitochondrial dysfunction. We make general recommendations about improved methodological approaches toward identification and regulation of chemicals that are gerontogenic to the brain.

Discovering the Neural Nature of Moral Cognition? Empirical, Theoretical, and Practical Challenges in Bioethical Research with Electroencephalography (EEG).

PubMed

Wagner, Nils-Frederic; Chaves, Pedro; Wolff, Annemarie

2017-06-01

In this article we critically review the neural mechanisms of moral cognition that have recently been studied via electroencephalography (EEG). Such studies promise to shed new light on traditional moral questions by helping us to understand how effective moral cognition is embodied in the brain. It has been argued that conflicting normative ethical theories require different cognitive features and can, accordingly, in a broadly conceived naturalistic attempt, be associated with different brain processes that are rooted in different brain networks and regions. This potentially morally relevant brain activity has been empirically investigated through EEG-based studies on moral cognition. From neuroscientific evidence gathered in these studies, a variety of normative conclusions have been drawn and bioethical applications have been suggested. We discuss methodological and theoretical merits and demerits of the attempt to use EEG techniques in a morally significant way, point to legal challenges and policy implications, indicate the potential to reveal biomarkers of psychopathological conditions, and consider issues that might inform future bioethical work.

Virtual reality and brain computer interface in neurorehabilitation

PubMed Central

Dahdah, Marie; Driver, Simon; Parsons, Thomas D.; Richter, Kathleen M.

2016-01-01

The potential benefit of technology to enhance recovery after central nervous system injuries is an area of increasing interest and exploration. The primary emphasis to date has been motor recovery/augmentation and communication. This paper introduces two original studies to demonstrate how advanced technology may be integrated into subacute rehabilitation. The first study addresses the feasibility of brain computer interface with patients on an inpatient spinal cord injury unit. The second study explores the validity of two virtual environments with acquired brain injury as part of an intensive outpatient neurorehabilitation program. These preliminary studies support the feasibility of advanced technologies in the subacute stage of neurorehabilitation. These modalities were well tolerated by participants and could be incorporated into patients' inpatient and outpatient rehabilitation regimens without schedule disruptions. This paper expands the limited literature base regarding the use of advanced technologies in the early stages of recovery for neurorehabilitation populations and speaks favorably to the potential integration of brain computer interface and virtual reality technologies as part of a multidisciplinary treatment program. PMID:27034541

Neuropsychopharmacological aesthetics: A theoretical consideration of pharmacological approaches to causative brain study in aesthetics and art.

PubMed

Spee, Blanca; Ishizu, Tomohiro; Leder, Helmut; Mikuni, Jan; Kawabata, Hideaki; Pelowski, Matthew

2018-01-01

Recent developments in neuroaesthetics have heightened the need for causative approaches to more deeply understand the mechanism underlying perception, emotion, and aesthetic experiences. This has recently been the topic for empirical work, employing several causative methods for changing brain activity, as well as comparative assessments of individuals with brain damage or disease. However, one area of study with high potential, and indeed a long history of often nonscientific use in the area of aesthetics and art, employing psychopharmacological chemicals as means of changing brain function, has not been systematically utilized. This chapter reviews the literature on this topic, analyzing neuroendocrinological (neurochemical) approaches and mechanisms that might be used to causatively study the aesthetic brain. We focus on four relevant neuromodulatory systems potentially related to aesthetic experience: the dopaminergic, serotonergic, cannabinoid, and the opioidergic system. We build a bridge to psychopharmacological methods and review drug-induced behavioral and neurobiological consequences. We conclude with a discussion of hypotheses and suggestions for future research. © 2018 Elsevier B.V. All rights reserved.

Olive-Oil-Derived Oleocanthal Enhances β-Amyloid Clearance as a Potential Neuroprotective Mechanism against Alzheimer’s Disease: In Vitro and in Vivo Studies

PubMed Central

2013-01-01

Oleocanthal, a phenolic component of extra-virgin olive oil, has been recently linked to reduced risk of Alzheimer’s disease (AD), a neurodegenerative disease that is characterized by accumulation of β-amyloid (Aβ) and tau proteins in the brain. However, the mechanism by which oleocanthal exerts its neuroprotective effect is still incompletely understood. Here, we provide in vitro and in vivo evidence for the potential of oleocanthal to enhance Aβ clearance from the brain via up-regulation of P-glycoprotein (P-gp) and LDL lipoprotein receptor related protein-1 (LRP1), major Aβ transport proteins, at the blood-brain barrier (BBB). Results from in vitro and in vivo studies demonstrated similar and consistent pattern of oleocanthal in controlling Aβ levels. In cultured mice brain endothelial cells, oleocanthal treatment increased P-gp and LRP1 expression and activity. Brain efflux index (BEI%) studies of 125I-Aβ40 showed that administration of oleocanthal extracted from extra-virgin olive oil to C57BL/6 wild-type mice enhanced 125I-Aβ40 clearance from the brain and increased the BEI% from 62.0 ± 3.0% for control mice to 79.9 ± 1.6% for oleocanthal treated mice. Increased P-gp and LRP1 expression in the brain microvessels and inhibition studies confirmed the role of up-regulation of these proteins in enhancing 125I-Aβ40 clearance after oleocanthal treatment. Furthermore, our results demonstrated significant increase in 125I-Aβ40 degradation as a result of the up-regulation of Aβ degrading enzymes following oleocanthal treatment. In conclusion, these findings provide experimental support that potential reduced risk of AD associated with extra-virgin olive oil could be mediated by enhancement of Aβ clearance from the brain. PMID:23414128

Brain Stimulation in Alzheimer's Disease.

PubMed

Chang, Chun-Hung; Lane, Hsien-Yuan; Lin, Chieh-Hsin

2018-01-01

Brain stimulation techniques can modulate cognitive functions in many neuropsychiatric diseases. Pilot studies have shown promising effects of brain stimulations on Alzheimer's disease (AD). Brain stimulations can be categorized into non-invasive brain stimulation (NIBS) and invasive brain stimulation (IBS). IBS includes deep brain stimulation (DBS), and invasive vagus nerve stimulation (VNS), whereas NIBS includes transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), electroconvulsive treatment (ECT), magnetic seizure therapy (MST), cranial electrostimulation (CES), and non-invasive VNS. We reviewed the cutting-edge research on these brain stimulation techniques and discussed their therapeutic effects on AD. Both IBS and NIBS may have potential to be developed as novel treatments for AD; however, mixed findings may result from different study designs, patients selection, population, or samples sizes. Therefore, the efficacy of NIBS and IBS in AD remains uncertain, and needs to be further investigated. Moreover, more standardized study designs with larger sample sizes and longitudinal follow-up are warranted for establishing a structural guide for future studies and clinical application.

Whole-brain diffusion tensor imaging in correlation to visual-evoked potentials in multiple sclerosis: a tract-based spatial statistics analysis.

PubMed

Lobsien, D; Ettrich, B; Sotiriou, K; Classen, J; Then Bergh, F; Hoffmann, K-T

2014-01-01

Functional correlates of microstructural damage of the brain affected by MS are incompletely understood. The purpose of this study was to evaluate correlations of visual-evoked potentials with microstructural brain changes as determined by DTI in patients with demyelinating central nervous disease. Sixty-one patients with clinically isolated syndrome or MS were prospectively recruited. The mean P100 visual-evoked potential latencies of the right and left eyes of each patient were calculated and used for the analysis. For DTI acquisition, a single-shot echo-planar imaging pulse sequence with 80 diffusion directions was performed at 3T. Fractional anisotropy, radial diffusivity, and axial diffusivity were calculated and correlated with mean P100 visual-evoked potentials by tract-based spatial statistics. Significant negative correlations between mean P100 visual-evoked potentials and fractional anisotropy and significant positive correlations between mean P100 visual-evoked potentials and radial diffusivity were found widespread over the whole brain. The highest significance was found in the optic radiation, frontoparietal white matter, and corpus callosum. Significant positive correlations between mean P100 visual-evoked potentials and axial diffusivity were less widespread, notably sparing the optic radiation. Microstructural changes of the whole brain correlated significantly with mean P100 visual-evoked potentials. The distribution of the correlations showed clear differences among axial diffusivity, fractional anisotropy, and radial diffusivity, notably in the optic radiation. This finding suggests a stronger correlation of mean P100 visual-evoked potentials to demyelination than to axonal damage. © 2014 by American Journal of Neuroradiology.

A coupled bimodal SPECT-CT imaging and brain kinetics studies of zolmitriptan-encapsulated nanostructured polymeric carriers.

PubMed

Mandlik, Satish K; Ranpise, Nisharani S; Mohanty, Bhabani S; Chaudhari, Pradip R

2018-06-01

The present investigation deals with preparation and characterization of anti-migraine zolmitriptan (ZMT) nanostructured polymeric carriers for nose to brain drug targeting. The drug-loaded colloidal nanocarriers of ZMT were prepared by modified ionic gelation of cationic chitosan with anionic sodium tripolyphosphate and characterized for particle size, zeta potential, and entrapment efficiency. Further, in order to investigate nose to brain drug targeting, biodistribution, and brain kinetics studies were performed using 99m technetium radiolabeled nanocarriers ( 99m Tc-ZMTNP) in Swiss albino mice. The results were compared with intranasal pure drug solution ( 99m Tc-ZMT) and intravenous nanocarriers ( 99m Tc-ZMTNP). A single photon emission computerized tomography (SPECT) radioimaging studies were also carried out to visualize and confirm brain uptake of nanocarriers. The optimized nanocarriers showed particle size of 161 nm, entrapment efficiency of 80.6%, and zeta potential of + 23.7 mV. The pharmacokinetic parameters, C max , and AUC 0-∞ values for ZMT concentration in the brain expressed as percent radioactivity per gram of brain in intranasal and intravenous route of administration were calculated. The brain C max and AUC 0-∞ values found in three groups, intranasal 99m Tc-ZMTNP, intranasal 99m Tc-ZMT, and intravenous 99m Tc-ZMTNP were (0.427 and 1.889), (0.272 and 0.7157), and (0.204 and 0.9333), respectively. The higher C max values of intranasal 99m Tc-ZMTNP suggests better brain uptake as compared to other routes of administration. The significant higher values of nose to brain targeting parameters namely, drug targeting index (5.57), drug targeting efficiency (557.08%), and nose to brain drug direct transport (82.05%) confirmed drug targeting to brain via nasal route. The coupled bimodal SPECT-CT scintigrams confirm the brain uptake of intranasal 99m Tc-ZMTNP demonstrating major radioactivity accumulation in brain. This study conclusively demonstrated the greater uptake of ZMT-loaded nanocarriers by nose to brain drug targeting, which proves promising drug delivery system.

Potential Beneficial Effects of Probiotics on Human Migraine Headache: A Literature Review.

PubMed

Dai, Yu-Jie; Wang, Hai-Yan; Wang, Xi-Jian; Kaye, Alan D; Sun, Yong-Hai

2017-02-01

Recent studies have shown that migraine headache is often associated with concomitant gastrointestinal diseases. There is a higher prevalence of headaches in patients with gastrointestinal disorders. These associations between migraine and gastrointestinal disorders suggest a potential link to a bidirectional modulation of gut microbiota and brain function. The underlying working mechanistic links between migraine and gastrointestinal diseases may include increased intestinal epithelial permeability and inflammation. This review presents an overview of the relationship between gut microbiota and brain function, especially with regard to migraine headache. Literature review. Anesthesia and Operation Center, Department of Anesthesiology, Chinese PLA General Hospital. The present investigation included a PubMed search using the following terms: migraine headache, gut microbiota, brain function, and probiotics. In this literature review, we mainly discussed the relationship between gut microbiota and brain function, especially with regard to migraine headache. The potential effects of probiotics supplement on migraine headache were also included. There is limited evidence from clinical studies of the positive effects of probiotics in patients with migraine headache. Large-scale randomized, placebo-controlled clinical trials are warranted to evaluate the clinical efficacy and safety of probiotics in patients with migraine headache. Similar to migraine headache, disorders of the brain involving depression and anxiety have been demonstrated to be associated with increased gut permeability. An improvement in gut microbiota and reduction of inflammation can have positive effects on strengthening gut and brain function. Moreover, it can be inferred that probiotics may have a beneficial effect on the frequency and severity of migraine headache attacks. Large-scale randomized, placebo-controlled studies are warranted in the future to evaluate the clinical efficacy and safety of probiotics in patients with migraine headache.Key words: Migraine headache, gut microbiota, brain function, probiotics.

Decade of the Brain 1990--2000: Maximizing human potential

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1991-04-01

The US Decade of the Brain offers scientists throughout the Federal Government a unique opportunity to advance and apply scientific knowledge about the brain and nervous system. During the next 10 years, scientists hope to maximize human potential through studies of human behavior, senses and communication, learning and memory, genetic/chemical alterations, and environmental interactions. Progress in these areas should lead to reductions in mortality from brain and nervous system disorders and to improvements in the quality of life. This report identifies nine research areas that could form the basis of an integrated program in the brain and behavioral sciences. Amore » chart summarizing the Federal activities in these nine areas may be found at the back of the report. In addition, three areas that span the nine research areas -- basic research, technology and international activities -- are considered.« less

Different Brain Wave Patterns and Cortical Control Abilities in Relation to Different Creative Potentials

ERIC Educational Resources Information Center

Li, Ying-Han; Tseng, Chao-Yuan; Tsai, Arthur Chih-Hsin; Huang, Andrew Chih-Wei; Lin, Wei-Lun

2016-01-01

Contemporary understanding of brain functions provides a way to probe into the mystery of creativity. However, the prior evidence regarding the relationship between creativity and brain wave patterns reveals inconsistent conclusions. One possible reason might be that the means of selecting creative individuals in the past has varied in each study.…

Non-invasive Brain Stimulation: Probing Intracortical Circuits and Improving Cognition in the Aging Brain

PubMed Central

Gomes-Osman, Joyce; Indahlastari, Aprinda; Fried, Peter J.; Cabral, Danylo L. F.; Rice, Jordyn; Nissim, Nicole R.; Aksu, Serkan; McLaren, Molly E.; Woods, Adam J.

2018-01-01

The impact of cognitive aging on brain function and structure is complex, and the relationship between aging-related structural changes and cognitive function are not fully understood. Physiological and pathological changes to the aging brain are highly variable, making it difficult to estimate a cognitive trajectory with which to monitor the conversion to cognitive decline. Beyond the information on the structural and functional consequences of cognitive aging gained from brain imaging and neuropsychological studies, non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) can enable stimulation of the human brain in vivo, offering useful insights into the functional integrity of intracortical circuits using electrophysiology and neuromodulation. TMS measurements can be used to identify and monitor changes in cortical reactivity, the integrity of inhibitory and excitatory intracortical circuits, the mechanisms of long-term potentiation (LTP)/depression-like plasticity and central cholinergic function. Repetitive TMS and tDCS can be used to modulate neuronal excitability and enhance cortical function, and thus offer a potential means to slow or reverse cognitive decline. This review will summarize and critically appraise relevant literature regarding the use of TMS and tDCS to probe cortical areas affected by the aging brain, and as potential therapeutic tools to improve cognitive function in the aging population. Challenges arising from intra-individual differences, limited reproducibility, and methodological differences will be discussed.

Cerebrospinal fluid biochemical studies in patients with Parkinson's disease: toward a potential search for biomarkers for this disease

PubMed Central

Jiménez-Jiménez, Félix J.; Alonso-Navarro, Hortensia; García-Martín, Elena; Agúndez, José A. G.

2014-01-01

The blood-brain barrier supplies brain tissues with nutrients and filters certain compounds from the brain back to the bloodstream. In several neurodegenerative diseases, including Parkinson's disease (PD), there are disruptions of the blood-brain barrier. Cerebrospinal fluid (CSF) has been widely investigated in PD and in other parkinsonian syndromes with the aim of establishing useful biomarkers for an accurate differential diagnosis among these syndromes. This review article summarizes the studies reported on CSF levels of many potential biomarkers of PD. The most consistent findings are: (a) the possible role of CSF urate on the progression of the disease; (b) the possible relations of CSF total tau and phosphotau protein with the progression of PD and with the preservation of cognitive function in PD patients; (c) the possible value of CSF beta-amyloid 1-42 as a useful marker of further cognitive decline in PD patients, and (d) the potential usefulness of CSF neurofilament (NFL) protein levels in the differential diagnosis between PD and other parkinsonian syndromes. Future multicentric, longitudinal, prospective studies with long-term follow-up and neuropathological confirmation would be useful in establishing appropriate biomarkers for PD. PMID:25426023

My Face or Yours? Event-Related Potential Correlates of Self-Face Processing

ERIC Educational Resources Information Center

Keyes, Helen; Brady, Nuala; Reilly, Richard B.; Foxe, John J.

2010-01-01

The neural basis of self-recognition is mainly studied using brain-imaging techniques which reveal much about the localization of self-processing in the brain. There are comparatively few studies using EEG which allow us to study the time course of self-recognition. In this study, participants monitored a sequence of images, including 20 distinct…

Neurophysiology of the esophagus.

PubMed

Brock, Christina; Brokjaer, Anne; Drewes, Asbjørn Mohr; Farmer, Adam D; Frøkjaer, Jens Brøndum; Gregersen, Hans; Lottrup, Christian

2014-09-01

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the methods and characteristics of esophageal afferents in humans; the pitfalls in characterization of mechanosensitive afferents; the sensitization of esophageal afferents in human studies; the brain source modeling in the understanding of the esophagus-brain axis; the use of evoked brain potentials in the esophagus; and measuring descending inhibition in animal and human studies. © 2014 New York Academy of Sciences.

The Effect of Emotional State on the Processing of Morphosyntactic and Semantic Reversal Anomalies in Japanese: Evidence from Event-Related Brain Potentials

ERIC Educational Resources Information Center

Yano, Masataka; Suzuki, Yui; Koizumi, Masatoshi

2018-01-01

The present study examined the locus responsible for the effect of emotional state on sentence processing in healthy native speakers of Japanese, using event-related brain potentials. The participants were induced into a happy, neutral, or sad mood and then subjected to electroencephalogram recording during which emotionally neutral sentences,…

In vivo imaging of reactive oxygen species in mouse brain by using [3H]Hydromethidine as a potential radical trapping radiotracer

PubMed Central

Abe, Kohji; Takai, Nozomi; Fukumoto, Kazumi; Imamoto, Natsumi; Tonomura, Misato; Ito, Miwa; Kanegawa, Naoki; Sakai, Katsunori; Morimoto, Kenji; Todoroki, Kenichiro; Inoue, Osamu

2014-01-01

To assess reactive oxygen species (ROS) production by detecting the fluorescent oxidation product, hydroethidine has been used extensively. The present study was undertaken to evaluate the potential of the hydroethidine derivative as a radiotracer to measure in vivo brain ROS production. [3H]-labeled N-methyl-2,3-diamino-6-phenyl-dihydrophenanthridine ([3H]Hydromethidine) was synthesized, and evaluated using in vitro radical-induced oxidization and in vivo brain ROS production model. In vitro studies have indicated that [3H]Hydromethidine is converted to oxidized products by a superoxide radical (O2•−) and a hydroxyl radical (OH•−) but not hydrogen peroxide (H2O2). In vivo whole-body distribution study showed that [3H]Hydromethidine rapidly penetrated the brain and then was washed out in normal mice. Microinjection of sodium nitroprusside (SNP) into the brain was performed to produce ROS such as OH•− via Fenton reaction. A significant accumulation of radioactivity immediately after [3H]Hydromethidine injection was seen in the side of the brain treated with SNP (5 and 20 nmol) compared with that in the contralateral side. These results indicated that [3H]Hydromethidine freely penetrated into the brain where it was rapidly converted to oxidized forms, which were trapped there in response to the production of ROS. Thus, [3H]Hydromethidine should be useful as a radical trapping radiotracer in the brain. PMID:25227606

Fear-potentiated startle processing in humans: Parallel fMRI and orbicularis EMG assessment during cue conditioning and extinction.

PubMed

Lindner, Katja; Neubert, Jörg; Pfannmöller, Jörg; Lotze, Martin; Hamm, Alfons O; Wendt, Julia

2015-12-01

Studying neural networks and behavioral indices such as potentiated startle responses during fear conditioning has a long tradition in both animal and human research. However, most of the studies in humans do not link startle potentiation and neural activity during fear acquisition and extinction. Therefore, we examined startle blink responses measured with electromyography (EMG) and brain activity measured with functional MRI simultaneously during differential conditioning. Furthermore, we combined these behavioral fear indices with brain network activity by analyzing the brain activity evoked by the startle probe stimulus presented during conditioned visual threat and safety cues as well as in the absence of visual stimulation. In line with previous research, we found a fear-induced potentiation of the startle blink responses when elicited during a conditioned threat stimulus and a rapid decline of amygdala activity after an initial differentiation of threat and safety cues in early acquisition trials. Increased activation during processing of threat cues was also found in the anterior insula, the anterior cingulate cortex (ACC), and the periaqueductal gray (PAG). More importantly, our results depict an increase of brain activity to probes presented during threatening in comparison to safety cues indicating an involvement of the anterior insula, the ACC, the thalamus, and the PAG in fear-potentiated startle processing during early extinction trials. Our study underlines that parallel assessment of fear-potentiated startle in fMRI paradigms can provide a helpful method to investigate common and distinct processing pathways in humans and animals and, thus, contributes to translational research. Copyright © 2015 Elsevier B.V. All rights reserved.

Removing the effect of response time on brain activity reveals developmental differences in conflict processing in the posterior medial prefrontal cortex.

PubMed

Carp, Joshua; Fitzgerald, Kate Dimond; Taylor, Stephan F; Weissman, Daniel H

2012-01-02

In functional magnetic resonance imaging (fMRI) studies, researchers often attempt to ensure that group differences in brain activity are not confounded with group differences in mean reaction time (RT). However, even when groups are matched for performance, they may differ in terms of the RT-BOLD relationship: the degree to which brain activity varies with RT on a trial-by-trial basis. Group activation differences might therefore be influenced by group differences in the relationship between brain activity and time on task. Here, we investigated whether correcting for this potential confound alters group differences in brain activity. Specifically, we reanalyzed data from a functional MRI study of response conflict in children and adults, in which conventional analyses indicated that conflict-related activity did not differ between groups. We found that the RT-BOLD relationship was weaker in children than in adults. Consequently, after removing the effect of RT on brain activity, children exhibited greater conflict-related activity than adults in both the posterior medial prefrontal cortex and the right dorsolateral prefrontal cortex. These results identify the RT-BOLD relationship as an important potential confound in fMRI studies of group differences. They also suggest that the magnitude of the RT-BOLD relationship may be a useful biomarker of brain maturity. Copyright © 2011 Elsevier Inc. All rights reserved.

Visual Evoked Potential and Magnetic Resonance Imaging are More Effective Markers of Multiple Sclerosis Progression than Laser Polarimetry with Variable Corneal Compensation.

PubMed

Kantorová, Ema; Ziak, Peter; Kurča, Egon; Koyšová, Mária; Hladká, Mária; Zeleňák, Kamil; Michalik, Jozef

2014-01-01

The aim of our study was to assess the role of laser polarimetry and visual evoked potentials (VEP) as potential biomarkers of disease progression in multiple sclerosis (MS). A total of 41 patients with MS (82 eyes) and 22 age-related healthy volunteers (44 eyes) completed the study. MS patients were divided into two groups, one (ON) with a history of optic neuritis (17 patients, 34 eyes) and another group (NON) without it (24 patients, 48 eyes). The MS patients and controls underwent laser polarimetry (GDx) examination of the retinal nerve fiber layer (RNFL). In the MS group, we also examined: Kurtzke "expanded disability status scale" (EDSS), the duration of the disorder, VEP - latency and amplitude, and conventional brain magnetic resonance imaging (MRI). Our results were statistically analyzed using ANOVA, Mann-Whitney, and Spearman correlation analyses. In the MS group, brain atrophy and new T2 brain lesions in MRI correlated with both VEP latencies and amplitudes. Separate comparisons revealed VEP latency testing to be less sensitive in ON than in NON-patients. In ON patients, VEP amplitudes correlated mildly with brain atrophy (r = -0.15) and strongly with brain new MRI lesions (r = -0.8). In NON-patients, highly significant correlation of new MRI brain lesions with VEP latencies (r = 0.63, r = 0.6) and amplitudes (r = -0.3, r = -4.2) was found. EDSS also correlated with brain atrophy in this group (r = 0.5). Our study did not find a correlation of GDx measures with MRI tests. The GDx method was not able to detect whole brain demyelinization and the degeneration process, but was only able to reveal the involvement of optic nerves in ON and NON-patients. In our study, we found that both methods (VEP and GDx) can be used for the detection of optic nerve damage, but VEP was found to be superior in evaluating whole brain demyelinization and axonal degeneration. Both VEP and MRI, but not GDx, have an important role in monitoring disease progression in MS patients, independent of the ON history.

Progesterone for Neuroprotection in Pediatric Traumatic Brain Injury

PubMed Central

Robertson, Courtney L.; Fidan, Emin; Stanley, Rachel M.; MHSA; Noje, Corina; Bayir, Hülya

2016-01-01

Objective To provide an overview of the preclinical literature on progesterone for neuroprotection after traumatic brain injury (TBI), and to describe unique features of developmental brain injury that should be considered when evaluating the therapeutic potential for progesterone treatment after pediatric TBI. Data Sources National Library of Medicine PubMed literature review. Data Selection The mechanisms of neuroprotection by progesterone are reviewed, and the preclinical literature using progesterone treatment in adult animal models of TBI are summarized. Unique features of the developing brain that could either enhance or limit the efficacy of neuroprotection by progesterone are discussed, and the limited preclinical literature using progesterone after acute injury to the developing brain is described. Finally, the current status of clinical trials of progesterone for adult TBI is reviewed. Data Extraction and Synthesis Progesterone is a pleotropic agent with beneficial effects on secondary injury cascades that occur after TBI, including cerebral edema, neuroinflammation, oxidative stress, and excitotoxicity. More than 40 studies have used progesterone for treatment after TBI in adult animal models, with results summarized in tabular form. However, very few studies have evaluated progesterone in pediatric animal models of brain injury. To date, two human Phase II trials of progesterone for adult TBI have been published, and two multi-center Phase III trials are underway. Conclusions The unique features of the developing brain from that of a mature adult brain make it necessary to independently study progesterone in clinically relevant, immature animal models of TBI. Additional preclinical studies could lead to the development of a novel neuroprotective therapy that could reduce the long-term disability in head-injured children, and could potentially provide benefit in other forms of pediatric brain injury (global ischemia, stroke, statue epilepticus). PMID:25581631

Could Cord Blood Cell Therapy Reduce Preterm Brain Injury?

PubMed Central

Li, Jingang; McDonald, Courtney A.; Fahey, Michael C.; Jenkin, Graham; Miller, Suzanne L.

2014-01-01

Major advances in neonatal care have led to significant improvements in survival rates for preterm infants, but this occurs at a cost, with a strong causal link between preterm birth and neurological deficits, including cerebral palsy (CP). Indeed, in high-income countries, up to 50% of children with CP were born preterm. The pathways that link preterm birth and brain injury are complex and multifactorial, but it is clear that preterm birth is strongly associated with damage to the white matter of the developing brain. Nearly 90% of preterm infants who later develop spastic CP have evidence of periventricular white matter injury. There are currently no treatments targeted at protecting the immature preterm brain. Umbilical cord blood (UCB) contains a diverse mix of stem and progenitor cells, and is a particularly promising source of cells for clinical applications, due to ethical and practical advantages over other potential therapeutic cell types. Recent studies have documented the potential benefits of UCB cells in reducing brain injury, particularly in rodent models of term neonatal hypoxia–ischemia. These studies indicate that UCB cells act via anti-inflammatory and immuno-modulatory effects, and release neurotrophic growth factors to support the damaged and surrounding brain tissue. The etiology of brain injury in preterm-born infants is less well understood than in term infants, but likely results from episodes of hypoperfusion, hypoxia–ischemia, and/or inflammation over a developmental period of white matter vulnerability. This review will explore current knowledge about the neuroprotective actions of UCB cells and their potential to ameliorate preterm brain injury through neonatal cell administration. We will also discuss the characteristics of UCB-derived from preterm and term infants for use in clinical applications. PMID:25346720

The blood-brain barrier and nasal drug delivery to the central nervous system.

PubMed

Miyake, Marcel Menon; Bleier, Benjamin S

2015-01-01

The blood-brain barrier (BBB) is a highly efficient system that separates the central nervous system (CNS) from general circulation and promotes selective transport of molecules that are essential for brain function. However, it also limits the distribution of systemically administered therapeutics to the brain; therefore, there is a restricted number of drugs available for the treatment of brain disorders. Several drug-targeting strategies have been developed to attempt to bypass the BBB, but none has proved sufficiently effective in reaching the brain. The objective of this study is to generally review these strategies of drug administration to the CNS. Noninvasive methods of drug delivery, such as chemical and biologic transport systems, do not represent a feasible platform, whereas for most drugs, it is still not possible to achieve therapeutic levels within the brain tissue after intravenous or oral administration, and the use of higher potency or more concentrated doses may cause serious toxic side effects. Direct intrathecal drug delivery through a catheter into the CNS also presents several problems. Intranasal drug delivery is a potential alternative method due to the direct transport into the cerebrospinal fluid (CSF) compartment along the olfactory pathway, but the study's conclusions are controversial. An endoscopic intranasal surgical procedure using established skull base surgery reconstruction techniques based on the use of a nasal mucosa surgical flap as the only obstacle between the nose and the subarachnoid space has appeared as a potential solution to increase the absorption of intranasal drugs to the CNS. Despite extensive efforts to develop new techniques to cross the BBB, none has proved sufficiently effective in reaching the brain, whereas minimizing adverse effects and the endoscopic mucosal grafting technique offers new potential promise.

Persistent hyperphagia in acquired brain injury; an observational case study of patients receiving inpatient rehabilitation.

PubMed

Rowell, Arleen M; Faruqui, Rafey A

2010-01-01

Morbid hunger or persistent hyperphagia is a relatively rare but potentially life threatening complication of acquired brain injury (ABI). This paper presents findings from an observational case study of patients with hyperphagia receiving inpatient neurobehavioural rehabilitation following their acquired brain injury. The case study has utilized dietetic and medical records of identified patients to confirm the persistent and serious nature of this presentation in order to extract important management principles. The findings confirmed that hyperphagia or morbid hunger posed potentially life-threatening health risks to the patient, primarily around weight control and fluid balance, and risks of aggression towards professional and family carers. Pharmacological or behaviour modification interventions were only partially successful in management of this presentation. The study identified a high need for environmental and cue exposure control in management of this condition.

Integrated analytical techniques with high sensitivity for studying brain translocation and potential impairment induced by intranasally instilled copper nanoparticles.

PubMed

Bai, Ru; Zhang, Lili; Liu, Ying; Li, Bai; Wang, Liming; Wang, Peng; Autrup, Herman; Beer, Christiane; Chen, Chunying

2014-04-07

Health impacts of inhalation exposure to engineered nanomaterials have attracted increasing attention. In this paper, integrated analytical techniques with high sensitivity were used to study the brain translocation and potential impairment induced by intranasally instilled copper nanoparticles (CuNPs). Mice were exposed to CuNPs in three doses (1, 10, 40 mg/kg bw). The body weight of mice decreased significantly in the 10 and 40 mg/kg group (p<0.05) but recovered slightly within exposure duration. Inductively coupled plasma mass spectrometry (ICP-MS) analysis showed that CuNPs could enter the brain. Altered distribution of some important metal elements was observed by synchrotron radiation X-ray fluorescence (SRXRF). H&E staining and immunohistochemical analysis showed that CuNPs produced damages to nerve cells and astrocyte might be the one of the potential targets of CuNPs. The changes of neurotransmitter levels in different brain regions demonstrate that the dysfunction occurred in exposed groups. These data indicated that CuNPs could enter the brain after nasal inhalation and induced damages to the central nervous system (CNS). Integration of effective analytical techniques for systematic investigations is a promising direction to better understand the biological activities of nanomaterials. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Mindfulness training for adolescents: A neurodevelopmental perspective on investigating modifications in attention and emotion regulation using event-related brain potentials.

PubMed

Sanger, Kevanne Louise; Dorjee, Dusana

2015-09-01

Mindfulness training is increasingly being introduced in schools, yet studies examining its impact on the developing brain have been scarce. A neurodevelopmental perspective on mindfulness has been advocated as a powerful tool to enhance our understanding of underlying neurocognitive changes that have implications for developmental well-being research and the implementation of mindfulness in education. To stimulate more research in the developmental cognitive neuroscience of mindfulness, this article outlines possible indexes of mindfulness-based change in adolescence, with a focus on event-related brain potential (ERP) markers. We provide methodological recommendations for future studies and offer examples of research paradigms. We also discuss how mindfulness practice could impact on the development of prefrontal brain structures and enhance attention control and emotion regulation skills in adolescents, impacting in turn on their self-regulation and coping skills. We highlight advantages of the ERP methodology in neurodevelopmental research of mindfulness. It is proposed that research using established experimental tasks targeting ERP components such as the contingent negative variability, N200, error-related negativity and error positivity, P300, and late positive potential could elucidate developmentally salient shifts in the neural plasticity of the adolescent brain induced by mindfulness practice.

A novel head-neck cooling device for concussion injury in contact sports

PubMed Central

Wang, Huan; Wang, Bonnie; Jackson, Kevin; Miller, Claire M.; Hasadsri, Linda; Llano, Daniel; Rubin, Rachael; Zimmerman, Jarred; Johnson, Curtis; Sutton, Brad

2015-01-01

Emerging research on the long-term impact of concussions on athletes has allowed public recognition of the potentially devastating effects of these and other mild head injuries. Mild traumatic brain injury (mTBI) is a multifaceted disease for which management remains a clinical challenge. Recent pre-clinical and clinical data strongly suggest a destructive synergism between brain temperature elevation and mTBI; conversely, brain hypothermia, with its broader, pleiotropic effects, represents the most potent neuro-protectant in laboratory studies to date. Although well-established in selected clinical conditions, a systemic approach to accomplish regional hypothermia has failed to yield an effective treatment strategy in traumatic brain injury (TBI). Furthermore, although systemic hypothermia remains a potentially valid treatment strategy for moderate to severe TBIs, it is neither practical nor safe for mTBIs. Therefore, selective head-neck cooling may represent an ideal strategy to provide therapeutic benefits to the brain. Optimizing brain temperature management using a National Aeronautics and Space Administration (NASA) spacesuit spinoff head-neck cooling technology before and/or after mTBI in contact sports may represent a sensible, practical, and effective method to potentially enhance recover and minimize post-injury deficits. In this paper, we discuss and summarize the anatomical, physiological, preclinical, and clinical data concerning NASA spinoff head-neck cooling technology as a potential treatment for mTBIs, particularly in the context of contact sports. PMID:28123788

Stem cell-based therapies for tumors in the brain: are we there yet?

PubMed

Shah, Khalid

2016-08-01

Advances in understanding adult stem cell biology have facilitated the development of novel cell-based therapies for cancer. Recent developments in conventional therapies (eg, tumor resection techniques, chemotherapy strategies, and radiation therapy) for treating both metastatic and primary tumors in the brain, particularly glioblastoma have not resulted in a marked increase in patient survival. Preclinical studies have shown that multiple stem cell types exhibit inherent tropism and migrate to the sites of malignancy. Recent studies have validated the feasibility potential of using engineered stem cells as therapeutic agents to target and eliminate malignant tumor cells in the brain. This review will discuss the recent progress in the therapeutic potential of stem cells for tumors in the brain and also provide perspectives for future preclinical studies and clinical translation. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Evaluation method for in situ electric field in standardized human brain for different transcranial magnetic stimulation coils

NASA Astrophysics Data System (ADS)

Iwahashi, Masahiro; Gomez-Tames, Jose; Laakso, Ilkka; Hirata, Akimasa

2017-03-01

This study proposes a method to evaluate the electric field induced in the brain by transcranial magnetic stimulation (TMS) to realize focal stimulation in the target area considering the inter-subject difference of the brain anatomy. The TMS is a non-invasive technique used for treatment/diagnosis, and it works by inducing an electric field in a specific area of the brain via a coil-induced magnetic field. Recent studies that report on the electric field distribution in the brain induced by TMS coils have been limited to simplified human brain models or a small number of detailed human brain models. Until now, no method has been developed that appropriately evaluates the coil performance for a group of subjects. In this study, we first compare the magnetic field and the magnetic vector potential distributions to determine if they can be used as predictors of the TMS focality derived from the electric field distribution. Next, the hotspots of the electric field on the brain surface of ten subjects using six coils are compared. Further, decisive physical factors affecting the focality of the induced electric field by different coils are discussed by registering the computed electric field in a standard brain space for the first time, so as to evaluate coil characteristics for a large population of subjects. The computational results suggest that the induced electric field in the target area cannot be generalized without considering the morphological variability of the human brain. Moreover, there was no remarkable difference between the various coils, although focality could be improved to a certain extent by modifying the coil design (e.g., coil radius). Finally, the focality estimated by the electric field was more correlated with the magnetic vector potential than the magnetic field in a homogeneous sphere.

Evaluation method for in situ electric field in standardized human brain for different transcranial magnetic stimulation coils.

PubMed

Iwahashi, Masahiro; Gomez-Tames, Jose; Laakso, Ilkka; Hirata, Akimasa

2017-03-21

This study proposes a method to evaluate the electric field induced in the brain by transcranial magnetic stimulation (TMS) to realize focal stimulation in the target area considering the inter-subject difference of the brain anatomy. The TMS is a non-invasive technique used for treatment/diagnosis, and it works by inducing an electric field in a specific area of the brain via a coil-induced magnetic field. Recent studies that report on the electric field distribution in the brain induced by TMS coils have been limited to simplified human brain models or a small number of detailed human brain models. Until now, no method has been developed that appropriately evaluates the coil performance for a group of subjects. In this study, we first compare the magnetic field and the magnetic vector potential distributions to determine if they can be used as predictors of the TMS focality derived from the electric field distribution. Next, the hotspots of the electric field on the brain surface of ten subjects using six coils are compared. Further, decisive physical factors affecting the focality of the induced electric field by different coils are discussed by registering the computed electric field in a standard brain space for the first time, so as to evaluate coil characteristics for a large population of subjects. The computational results suggest that the induced electric field in the target area cannot be generalized without considering the morphological variability of the human brain. Moreover, there was no remarkable difference between the various coils, although focality could be improved to a certain extent by modifying the coil design (e.g., coil radius). Finally, the focality estimated by the electric field was more correlated with the magnetic vector potential than the magnetic field in a homogeneous sphere.

Mesenchymal Stromal Cell-Derived Extracellular Vesicles Protect the Fetal Brain After Hypoxia-Ischemia.

PubMed

Ophelders, Daan R M G; Wolfs, Tim G A M; Jellema, Reint K; Zwanenburg, Alex; Andriessen, Peter; Delhaas, Tammo; Ludwig, Anna-Kristin; Radtke, Stefan; Peters, Vera; Janssen, Leon; Giebel, Bernd; Kramer, Boris W

2016-06-01

Preterm neonates are susceptible to perinatal hypoxic-ischemic brain injury, for which no treatment is available. In a preclinical animal model of hypoxic-ischemic brain injury in ovine fetuses, we have demonstrated the neuroprotective potential of systemically administered mesenchymal stromal cells (MSCs). The mechanism of MSC treatment is unclear but suggested to be paracrine, through secretion of extracellular vesicles (EVs). Therefore, we investigated in this study the protective effects of mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) in a preclinical model of preterm hypoxic-ischemic brain injury. Ovine fetuses were subjected to global hypoxia-ischemia by transient umbilical cord occlusion, followed by in utero intravenous administration of MSC-EVs. The therapeutic effects of MSC-EV administration were assessed by analysis of electrophysiological parameters and histology of the brain. Systemic administration of MSC-EVs improved brain function by reducing the total number and duration of seizures, and by preserving baroreceptor reflex sensitivity. These functional protections were accompanied by a tendency to prevent hypomyelination. Cerebral inflammation remained unaffected by the MSC-EV treatment. Our data demonstrate that MSC-EV treatment might provide a novel strategy to reduce the neurological sequelae following hypoxic-ischemic injury of the preterm brain. Our study results suggest that a cell-free preparation comprising neuroprotective MSC-EVs could substitute MSCs in the treatment of preterm neonates with hypoxic-ischemic brain injury, thereby circumventing the potential risks of systemic administration of living cells. Bone marrow-derived mesenchymal stromal cells (MSCs) show promise in treating hypoxic-ischemic injury of the preterm brain. Study results suggest administration of extracellular vesicles, rather than intact MSCs, is sufficient to exert therapeutic effects and avoids potential concerns associated with administration of living cells. The therapeutic efficacy of systemically administered mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) on hypoxia-ischemia-induced injury was assessed in the preterm ovine brain. Impaired function and structural injury of the fetal brain was improved following global hypoxia-ischemia. A cell-free preparation of MSC-EVs could substitute for the cellular counterpart in the treatment of preterm neonates with hypoxic-ischemic brain injury. This may open new clinical applications for "off-the-shelf" interventions with MSC-EVs. ©AlphaMed Press.

Investigating large-scale brain dynamics using field potential recordings: analysis and interpretation.

PubMed

Pesaran, Bijan; Vinck, Martin; Einevoll, Gaute T; Sirota, Anton; Fries, Pascal; Siegel, Markus; Truccolo, Wilson; Schroeder, Charles E; Srinivasan, Ramesh

2018-06-25

New technologies to record electrical activity from the brain on a massive scale offer tremendous opportunities for discovery. Electrical measurements of large-scale brain dynamics, termed field potentials, are especially important to understanding and treating the human brain. Here, our goal is to provide best practices on how field potential recordings (electroencephalograms, magnetoencephalograms, electrocorticograms and local field potentials) can be analyzed to identify large-scale brain dynamics, and to highlight critical issues and limitations of interpretation in current work. We focus our discussion of analyses around the broad themes of activation, correlation, communication and coding. We provide recommendations for interpreting the data using forward and inverse models. The forward model describes how field potentials are generated by the activity of populations of neurons. The inverse model describes how to infer the activity of populations of neurons from field potential recordings. A recurring theme is the challenge of understanding how field potentials reflect neuronal population activity given the complexity of the underlying brain systems.

Functional neuroimaging in multiple sclerosis with radiolabelled glia markers: preliminary comparative PET studies with [11C]vinpocetine and [11C]PK11195 in patients.

PubMed

Vas, Adám; Shchukin, Yevgeni; Karrenbauer, Virginija D; Cselényi, Zsolt; Kostulas, Kosta; Hillert, Jan; Savic, Ivanka; Takano, Akihiro; Halldin, Christer; Gulyás, Balázs

2008-01-15

With the purpose of demonstrating the use of positron emission tomography (PET) and radiolabelled glia markers to indicate regional cerebral damage, we measured with PET in four young multiplex sclerosis (MS) patients in two consecutive measurements the global and regional brain uptake as well as regional distribution and binding potential (BP) of [(11)C]vinpocetine and [(11)C]PK11195. Both ligands showed increased uptake and BP in the regions of local brain damage. However, regional BP values for [(11)C]vinpocetine were markedly higher than those for [(11)C]PK11195. This feature of the former radioligand may be related to its high brain uptake and marked affinity to the peripheral benzodiazepine receptor binding sites (PBBS), characteristic for glia cells. As local brain traumas entail reactive glia accumulation in and around the site of the damage, the present findings may indicate that [(11)C]vinpocetine marks the place or boundaries of local brain damage by binding to the PBBS present in glia cells, which, in turn, accumulate in the region of the damage. The present findings (i) confirm earlier observations with [(11)C]PK11195 as a potential glia marker in PET studies and (ii) support the working hypothesis that [(11)C]vinpocetine is a potentially useful PET marker of regional and global brain damage resulting in glia accumulation locally or globally in the human brain. The comparative analysis of the two ligands indicate that [(11)C]vinpocetine shows a number of characteristics favourable in comparison with [(11)C]PK11195.

Concentrating mixtures of neuroactive pharmaceuticals and altered neurotransmitter levels in the brain of fish exposed to a wastewater effluent.

PubMed

David, Arthur; Lange, Anke; Tyler, Charles R; Hill, Elizabeth M

2018-04-15

Fish can be exposed to a variety of neuroactive pharmaceuticals via the effluent discharges from wastewater treatment plants and concerns have arisen regarding their potential impacts on fish behaviour and ecology. In this study, we investigated the uptake of 14 neuroactive pharmaceuticals from a treated wastewater effluent into blood plasma and brain regions of roach (Rutilus rutilus) after exposure for 15days. We show that a complex mixture of pharmaceuticals including, 6 selective serotonin reuptake inhibitors, a serotonin-noradrenaline reuptake inhibitor, 3 atypical antipsychotics, 2 tricyclic antidepressants and a benzodiazepine, concentrate in different regions of the brain including the telencephalon, hypothalamus, optic tectum and hindbrain of effluent-exposed fish. Pharmaceuticals, with the exception of nordiazepam, were between 3-40 fold higher in brain compared with blood plasma, showing these neuroactive drugs are readily uptaken, into brain tissues in fish. To assess for the potential for any adverse ecotoxicological effects, the effect ratio was calculated from human therapeutic plasma concentrations (HtPCs) and the measured or predicted fish plasma concentrations of pharmaceuticals. After accounting for a safety factor of 1000, the effect ratios indicated that fluoxetine, norfluoxetine, sertraline, and amitriptyline warrant prioritisation for risk assessment studies. Furthermore, although plasma concentrations of all the pharmaceuticals were between 33 and 5714-fold below HtPCs, alterations in serotonin, glutamate, acetylcholine and tryptophan concentrations were observed in different brain regions of effluent-exposed fish. This study highlights the importance of determining the potential health effects arising from the concentration of complex environmental mixtures in risk assessment studies. Copyright © 2017 Elsevier B.V. All rights reserved.

3D brain oxygenation measurements in awake hypertensive mice using two photon phosphorescence lifetime imaging

NASA Astrophysics Data System (ADS)

Lu, Xuecong; Moeini, Mohammad; Li, Baoqiang; Zhang, Cong; Sakadžić, Sava; Lesage, Frédéric

2018-02-01

Cardiovascular risk factors, such as hypertension, have been associated with cognitive decline, potentially due to their impact on brain tissue oxygenation. In this study, high spatial resolution imaging in three dimensions was used to understand changes in brain oxygenation with hypertension. Experiments were performed on Young (WT_Y, 3-4 months, n=8), Old (WT_O, 6-7 months, n=8), and Old with hypertension (HP_O, 6-7 months, n=8) C57bL/6 awake mice. Two photon phosphorescence lifetime microscopy using an O2-sensitive phosphorescent dye PtPC343 was employed to measure two dimensional grids of PO2 in capillary beds (400um*400um, 25*25 pixels, acquired in 4 mins) and decays from arterioles. Scans were obtained continuously at depths from 50 um to 300 um under the brain surface. Using 3D measurements and a 250 um depth stack, we removed the compounding effects on brain oxygenation diffusion from surrounding brain vessels. The entire measurement of each vasculature stack required less than 30 minutes. This study indicates that among vascular risk factors, hypertension can reduce oxygen delivery and could potentially contribute to cognition decline.

[Possibilities of magnetic-laser therapy in comprehensive treatment of patients with brain concussion in acute period].

PubMed

Zubkova, O V; Samosiuk, I Z; Polishchuk, O V; Shul'ga, N M; Samosiuk, N I

2012-01-01

The efficacy of magnetic-laser therapy used according to the method developed by us was studied in patients having the brain concussion (BC) in an acute period. The study was based on the dynamics of values of the evoked vestibular potentials and the disease clinical course. It was shown that following the magnetic-laser therapy in combination with traditional pharmacotherapy in BC acute period, the statistically significant positive changes were registered in the quantitative characteristics of the evoked vestibular brain potentials that correlated with the dynamics of the disease clinical course. The data obtained substantiate the possibility of using the magnetic-laser therapy in patients with a mild craniocereblal injury in an acute period.

Brain surface temperature under a craniotomy

PubMed Central

Kalmbach, Abigail S.

2012-01-01

Many neuroscientists access surface brain structures via a small cranial window, opened in the bone above the brain region of interest. Unfortunately this methodology has the potential to perturb the structure and function of the underlying brain tissue. One potential perturbation is heat loss from the brain surface, which may result in local dysregulation of brain temperature. Here, we demonstrate that heat loss is a significant problem in a cranial window preparation in common use for electrical recording and imaging studies in mice. In the absence of corrective measures, the exposed surface of the neocortex was at ∼28°C, ∼10°C below core body temperature, and a standing temperature gradient existed, with tissue below the core temperature even several millimeters into the brain. Cooling affected cellular and network function in neocortex and resulted principally from increased heat loss due to convection and radiation through the skull and cranial window. We demonstrate that constant perfusion of solution, warmed to 37°C, over the brain surface readily corrects the brain temperature, resulting in a stable temperature of 36–38°C at all depths. Our results indicate that temperature dysregulation may be common in cranial window preparations that are in widespread use in neuroscience, underlining the need to take measures to maintain the brain temperature in many physiology experiments. PMID:22972953

Naringin alleviates early brain injury after experimental subarachnoid hemorrhage by reducing oxidative stress and inhibiting apoptosis.

PubMed

Han, Yuwei; Su, Jingyuan; Liu, Xiujuan; Zhao, Yuan; Wang, Chenchen; Li, Xiaoming

2017-07-01

This study aims to clarify the neuroprotective effect of naringin on early brain injury (EBI) following subarachnoid hemorrhage (SAH) and the possible mechanisms of naringin in the treatment of SAH. The endovascular puncture model was performed to induce SAH model in rats and the efficacy of 40mg/kg and 80mg/kg naringin were tested by intraperitoneally administration. SAH grade, neurological score, brain edema, blood-brain barrier permeability, the changes of oxidative stress related factors, apoptosis-related proteins, mitogen-activated protein kinase (MAPK) signaling pathway and neuronal morphology were detected to analyze the potential effect of naringin against SAH. The results demonstrated that naringin significantly ameliorated EBI, including SAH severity, neurologic deficits, brain edema and blood-brain barrier integrity by attenuating SAH-induced oxidative stress and apoptosis, and reduced the oxidant damage and apoptosis by inhibiting the activation of MAPK signaling pathway, which suggested a therapeutic potential of naringin in providing neuroprotection after SAH. Copyright © 2016 Elsevier Inc. All rights reserved.

Demonstration of brain noise on human EEG signals in perception of bistable images

NASA Astrophysics Data System (ADS)

Grubov, Vadim V.; Runnova, Anastasiya E.; Kurovskaya, Maria K.; Pavlov, Alexey N.; Koronovskii, Alexey A.; Hramov, Alexander E.

2016-03-01

In this report we studied human brain activity in the case of bistable visual perception. We proposed a new approach for quantitative characterization of this activity based on analysis of EEG oscillatory patterns and evoked potentials. Accordingly to theoretical background, obtained experimental EEG data and results of its analysis we studied a characteristics of brain activity during decision-making. Also we have shown that decisionmaking process has the special patterns on the EEG data.

Electroretinography and Visual Evoked Potentials in Childhood Brain Tumor Survivors.

PubMed

Pietilä, Sari; Lenko, Hanna L; Oja, Sakari; Koivisto, Anna-Maija; Pietilä, Timo; Mäkipernaa, Anne

2016-07-01

This population-based cross-sectional study evaluates the clinical value of electroretinography and visual evoked potentials in childhood brain tumor survivors. A flash electroretinography and a checkerboard reversal pattern visual evoked potential (or alternatively a flash visual evoked potential) were done for 51 survivors (age 3.8-28.7 years) after a mean follow-up time of 7.6 (1.5-15.1) years. Abnormal electroretinography was obtained in 1 case, bilaterally delayed abnormal visual evoked potentials in 22/51 (43%) cases. Nine of 25 patients with infratentorial tumor location, and altogether 12 out of 31 (39%) patients who did not have tumors involving the visual pathways, had abnormal visual evoked potentials. Abnormal electroretinographies are rarely observed, but abnormal visual evoked potentials are common even without evident anatomic lesions in the visual pathway. Bilateral changes suggest a general and possibly multifactorial toxic/adverse effect on the visual pathway. Electroretinography and visual evoked potential may have clinical and scientific value while evaluating long-term effects of childhood brain tumors and tumor treatment. © The Author(s) 2016.

Systematic Approach for the Formulation and Optimization of Solid Lipid Nanoparticles of Efavirenz by High Pressure Homogenization Using Design of Experiments for Brain Targeting and Enhanced Bioavailability

PubMed Central

Gupta, Shweta; Kesarla, Rajesh; Chotai, Narendra; Misra, Ambikanandan

2017-01-01

The nonnucleoside reverse transcriptase inhibitors, used for the treatment of HIV infections, are reported to have low bioavailability pertaining to high first-pass metabolism, high protein binding, and enzymatic metabolism. They also show low permeability across blood brain barrier. The CNS is reported to be the most important HIV reservoir site. In the present study, solid lipid nanoparticles of efavirenz were prepared with the objective of providing increased permeability and protection of drug due to biocompatible lipidic content and nanoscale size and thus developing formulation having potential for enhanced bioavailability and brain targeting. Solid lipid nanoparticles were prepared by high pressure homogenization technique using a systematic approach of design of experiments (DoE) and evaluated for particle size, polydispersity index, zeta potential, and entrapment efficiency. Particles of average size 108.5 nm having PDI of 0.172 with 64.9% entrapment efficiency were produced. Zeta potential was found to be −21.2 mV and the formulation was found stable. The in-vivo pharmacokinetic studies revealed increased concentration of the drug in brain, as desired, when administered through intranasal route indicating its potential for an attempt towards complete eradication of HIV and cure of HIV-infected patients. PMID:28243600

Teaching About “Brain and Learning” in High School Biology Classes: Effects on Teachers' Knowledge and Students' Theory of Intelligence

PubMed Central

Dekker, Sanne; Jolles, Jelle

2015-01-01

This study evaluated a new teaching module about “Brain and Learning” using a controlled design. The module was implemented in high school biology classes and comprised three lessons: (1) brain processes underlying learning; (2) neuropsychological development during adolescence; and (3) lifestyle factors that influence learning performance. Participants were 32 biology teachers who were interested in “Brain and Learning” and 1241 students in grades 8–9. Teachers' knowledge and students' beliefs about learning potential were examined using online questionnaires. Results indicated that before intervention, biology teachers were significantly less familiar with how the brain functions and develops than with its structure and with basic neuroscientific concepts (46 vs. 75% correct answers). After intervention, teachers' knowledge of “Brain and Learning” had significantly increased (64%), and more students believed that intelligence is malleable (incremental theory). This emphasizes the potential value of a short teaching module, both for improving biology teachers' insights into “Brain and Learning,” and for changing students' beliefs about intelligence. PMID:26648900

Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential.

PubMed

Lojewski, Xenia; Srimasorn, Sumitra; Rauh, Juliane; Francke, Silvan; Wobus, Manja; Taylor, Verdon; Araúzo-Bravo, Marcos J; Hallmeyer-Elgner, Susanne; Kirsch, Matthias; Schwarz, Sigrid; Schwarz, Johannes; Storch, Alexander; Hermann, Andreas

2015-10-01

Brain perivascular cells have recently been identified as a novel mesodermal cell type in the human brain. These cells reside in the perivascular niche and were shown to have mesodermal and, to a lesser extent, tissue-specific differentiation potential. Mesenchymal stem cells (MSCs) are widely proposed for use in cell therapy in many neurological disorders; therefore, it is of importance to better understand the "intrinsic" MSC population of the human brain. We systematically characterized adult human brain-derived pericytes during in vitro expansion and differentiation and compared these cells with fetal and adult human brain-derived neural stem cells (NSCs) and adult human bone marrow-derived MSCs. We found that adult human brain pericytes, which can be isolated from the hippocampus and from subcortical white matter, are-in contrast to adult human NSCs-easily expandable in monolayer cultures and show many similarities to human bone marrow-derived MSCs both regarding both surface marker expression and after whole transcriptome profile. Human brain pericytes showed a negligible propensity for neuroectodermal differentiation under various differentiation conditions but efficiently generated mesodermal progeny. Consequently, human brain pericytes resemble bone marrow-derived MSCs and might be very interesting for possible autologous and endogenous stem cell-based treatment strategies and cell therapeutic approaches for treating neurological diseases. Perivascular mesenchymal stem cells (MSCs) recently gained significant interest because of their appearance in many tissues including the human brain. MSCs were often reported as being beneficial after transplantation in the central nervous system in different neurological diseases; therefore, adult brain perivascular cells derived from human neural tissue were systematically characterized concerning neural stem cell and MSC marker expression, transcriptomics, and mesodermal and inherent neuroectodermal differentiation potential in vitro and in vivo after in utero transplantation. This study showed the lack of an innate neuronal but high mesodermal differentiation potential. Because of their relationship to mesenchymal stem cells, these adult brain perivascular mesodermal cells are of great interest for possible autologous therapeutic use. ©AlphaMed Press.

A place for the hippocampus in the cocaine addiction circuit: Potential roles for adult hippocampal neurogenesis.

PubMed

Castilla-Ortega, Estela; Serrano, Antonia; Blanco, Eduardo; Araos, Pedro; Suárez, Juan; Pavón, Francisco J; Rodríguez de Fonseca, Fernando; Santín, Luis J

2016-07-01

Cocaine addiction is a chronic brain disease in which the drug seeking habits and profound cognitive, emotional and motivational alterations emerge from drug-induced neuroadaptations on a vulnerable brain. Therefore, a 'cocaine addiction brain circuit' has been described to explain this disorder. Studies in both cocaine patients and rodents reveal the hippocampus as a main node in the cocaine addiction circuit. The contribution of the hippocampus to cocaine craving and the associated memories is essential to understand the chronic relapsing nature of addiction, which is the main obstacle for the recovery. Interestingly, the hippocampus holds a particular form of plasticity that is rare in the adult brain: the ability to generate new functional neurons. There is an active scientific debate on the contributions of these new neurons to the addicted brain. This review focuses on the potential role(s) of adult hippocampal neurogenesis (AHN) in cocaine addiction. Although the current evidence primarily originates from animal research, these preclinical studies support AHN as a relevant component for the hippocampal effects of cocaine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Atypical Laterality of Resting Gamma Oscillations in Autism Spectrum Disorders

ERIC Educational Resources Information Center

Maxwell, Christina R.; Villalobos, Michele E.; Schultz, Robert T.; Herpertz-Dahlmann, Beate; Konrad, Kerstin; Kohls, Gregor

2015-01-01

Abnormal brain oscillatory activity has been found in autism spectrum disorders (ASD) and proposed as a potential biomarker. While several studies have investigated gamma oscillations in ASD, none have examined resting gamma power across multiple brain regions. This study investigated resting gamma power using EEG in 15 boys with ASD and 18 age…

Education, the Brain and Dementia: Neuroprotection or Compensation?

ERIC Educational Resources Information Center

Brayne, Carol; Ince, Paul G.; Keage, Hannah A. D.; McKeith, Ian G.; Matthews, Fiona E.; Polvikoski, Tuomo; Sulkava, Raimo

2010-01-01

The potential protective role of education for dementia is an area of major interest. Almost all older people have some pathology in their brain at death but have not necessarily died with dementia. We have explored these two observations in large population-based cohort studies (Epidemiological Clinicopathological Studies in Europe; EClipSE) in…

Childhood Brain Tumor Epidemiology: A Brain Tumor Epidemiology Consortium Review

PubMed Central

Johnson, Kimberly J.; Cullen, Jennifer; Barnholtz-Sloan, Jill S.; Ostrom, Quinn T.; Langer, Chelsea E.; Turner, Michelle C.; McKean-Cowdin, Roberta; Fisher, James L.; Lupo, Philip J.; Partap, Sonia; Schwartzbaum, Judith A.; Scheurer, Michael E.

2014-01-01

Childhood brain tumors are the most common pediatric solid tumor and include several histological subtypes. Although progress has been made in improving survival rates for some subtypes, understanding of risk factors for childhood brain tumors remains limited to a few genetic syndromes and ionizing radiation to the head and neck. In this report, we review descriptive and analytical epidemiology childhood brain tumor studies from the past decade and highlight priority areas for future epidemiology investigations and methodological work that is needed to advance our understanding of childhood brain tumor causes. Specifically, we summarize the results of a review of studies published since 2004 that have analyzed incidence and survival in different international regions and that have examined potential genetic, immune system, developmental and birth characteristics, and environmental risk factors. PMID:25192704

Discovery of new candidate genes related to brain development using protein interaction information.

PubMed

Chen, Lei; Chu, Chen; Kong, Xiangyin; Huang, Tao; Cai, Yu-Dong

2015-01-01

Human brain development is a dramatic process composed of a series of complex and fine-tuned spatiotemporal gene expressions. A good comprehension of this process can assist us in developing the potential of our brain. However, we have only limited knowledge about the genes and gene functions that are involved in this biological process. Therefore, a substantial demand remains to discover new brain development-related genes and identify their biological functions. In this study, we aimed to discover new brain-development related genes by building a computational method. We referred to a series of computational methods used to discover new disease-related genes and developed a similar method. In this method, the shortest path algorithm was executed on a weighted graph that was constructed using protein-protein interactions. New candidate genes fell on at least one of the shortest paths connecting two known genes that are related to brain development. A randomization test was then adopted to filter positive discoveries. Of the final identified genes, several have been reported to be associated with brain development, indicating the effectiveness of the method, whereas several of the others may have potential roles in brain development.

Brain-penetrating 2-aminobenzimidazole H(1)-antihistamines for the treatment of insomnia.

PubMed

Coon, Timothy; Moree, Wilna J; Li, Binfeng; Yu, Jinghua; Zamani-Kord, Said; Malany, Siobhan; Santos, Mark A; Hernandez, Lisa M; Petroski, Robert E; Sun, Aixia; Wen, Jenny; Sullivan, Sue; Haelewyn, Jason; Hedrick, Michael; Hoare, Samuel J; Bradbury, Margaret J; Crowe, Paul D; Beaton, Graham

2009-08-01

The benzimidazole core of the selective non-brain-penetrating H(1)-antihistamine mizolastine was used to identify a series of brain-penetrating H(1)-antihistamines for the potential treatment of insomnia. Using cassette PK studies, brain-penetrating H(1)-antihistamines were identified and in vivo efficacy was demonstrated in a rat EEG/EMG model. Further optimization focused on strategies to attenuate an identified hERG liability, leading to the discovery of 4i with a promising in vitro profile.

Bedside functional brain imaging in critically-ill children using high-density EEG source modeling and multi-modal sensory stimulation.

PubMed

Eytan, Danny; Pang, Elizabeth W; Doesburg, Sam M; Nenadovic, Vera; Gavrilovic, Bojan; Laussen, Peter; Guerguerian, Anne-Marie

2016-01-01

Acute brain injury is a common cause of death and critical illness in children and young adults. Fundamental management focuses on early characterization of the extent of injury and optimizing recovery by preventing secondary damage during the days following the primary injury. Currently, bedside technology for measuring neurological function is mainly limited to using electroencephalography (EEG) for detection of seizures and encephalopathic features, and evoked potentials. We present a proof of concept study in patients with acute brain injury in the intensive care setting, featuring a bedside functional imaging set-up designed to map cortical brain activation patterns by combining high density EEG recordings, multi-modal sensory stimulation (auditory, visual, and somatosensory), and EEG source modeling. Use of source-modeling allows for examination of spatiotemporal activation patterns at the cortical region level as opposed to the traditional scalp potential maps. The application of this system in both healthy and brain-injured participants is demonstrated with modality-specific source-reconstructed cortical activation patterns. By combining stimulation obtained with different modalities, most of the cortical surface can be monitored for changes in functional activation without having to physically transport the subject to an imaging suite. The results in patients in an intensive care setting with anatomically well-defined brain lesions suggest a topographic association between their injuries and activation patterns. Moreover, we report the reproducible application of a protocol examining a higher-level cortical processing with an auditory oddball paradigm involving presentation of the patient's own name. This study reports the first successful application of a bedside functional brain mapping tool in the intensive care setting. This application has the potential to provide clinicians with an additional dimension of information to manage critically-ill children and adults, and potentially patients not suited for magnetic resonance imaging technologies.

Tetrapentylammonium block of chloramine-T and veratridine modified rat brain type IIA sodium channels

PubMed Central

Ghatpande, A S; Rao, S; Sikdar, S K

2001-01-01

Tetrapentylammonium (TPeA) block of rat brain type IIA sodium channel α subunit was studied using whole cell patch clamp. Results indicate that TPeA blocks the inactivating brain sodium channel in a potential and use-dependent manner similar to that of the cardiac sodium channel. Removal of inactivation using chloramine-T (CT) unmasks a time-dependent block by TPeA consistent with slow blocking kinetics. On the other hand, no time dependence is observed when inactivation is abolished by modification with veratridine. TPeA does not bind in a potential-dependent fashion to veratridine-modified channels and does not significantly affect gating of veratridine-modified channels suggesting that high affinity binding of TPeA to the brain sodium channel is lost after veratridine modification. PMID:11309247

Brain in situ hybridization maps as a source for reverse-engineering transcriptional regulatory networks: Alzheimer's disease insights

DOE Office of Scientific and Technical Information (OSTI.GOV)

Acquaah-Mensah, George K.; Taylor, Ronald C.

Microarray data have been a valuable resource for identifying transcriptional regulatory relationships among genes. As an example, brain region-specific transcriptional regulatory events have the potential of providing etiological insights into Alzheimer Disease (AD). However, there is often a paucity of suitable brain-region specific expression data obtained via microarrays or other high throughput means. The Allen Brain Atlas in situ hybridization (ISH) data sets (Jones et al., 2009) represent a potentially valuable alternative source of high-throughput brain region-specific gene expression data for such purposes. In this study, Allen BrainAtlasmouse ISH data in the hippocampal fields were extracted, focusing on 508 genesmore » relevant to neurodegeneration. Transcriptional regulatory networkswere learned using three high-performing network inference algorithms. Only 17% of regulatory edges from a network reverse-engineered based on brain region-specific ISH data were also found in a network constructed upon gene expression correlations inmousewhole brain microarrays, thus showing the specificity of gene expression within brain sub-regions. Furthermore, the ISH data-based networks were used to identify instructive transcriptional regulatory relationships. Ncor2, Sp3 and Usf2 form a unique three-party regulatory motif, potentially affecting memory formation pathways. Nfe2l1, Egr1 and Usf2 emerge among regulators of genes involved in AD (e.g. Dhcr24, Aplp2, Tia1, Pdrx1, Vdac1, andSyn2). Further, Nfe2l1, Egr1 and Usf2 are sensitive to dietary factors and could be among links between dietary influences and genes in the AD etiology. Thus, this approach of harnessing brain region-specific ISH data represents a rare opportunity for gleaning unique etiological insights for diseases such as AD.« less

Dimethyl sulfoxide (DMSO) as a potential contrast agent for brain tumors.

PubMed

Delgado-Goñi, T; Martín-Sitjar, J; Simões, R V; Acosta, M; Lope-Piedrafita, S; Arús, C

2013-02-01

Dimethyl sulfoxide (DMSO) is commonly used in preclinical studies of animal models of high-grade glioma as a solvent for chemotherapeutic agents. A strong DMSO signal was detected by single-voxel MRS in the brain of three C57BL/6 control mice during a pilot study of DMSO tolerance after intragastric administration. This led us to investigate the accumulation and wash-out kinetics of DMSO in both normal brain parenchyma (n=3 control mice) by single-voxel MRS, and in 12 GL261 glioblastomas (GBMs) by single-voxel MRS (n=3) and MRSI (n=9). DMSO accumulated differently in each tissue type, reaching its highest concentration in tumors: 6.18 ± 0.85 µmol/g water, 1.5-fold higher than in control mouse brain (p<0.05). A faster wash-out was detected in normal brain parenchyma with respect to GBM tissue: half-lives of 2.06 ± 0.58 and 4.57 ± 1.15 h, respectively. MRSI maps of time-course DMSO changes revealed clear hotspots of differential spatial accumulation in GL261 tumors. Additional MRSI studies with four mice bearing oligodendrogliomas (ODs) revealed similar results as in GBM tumors. The lack of T(1) contrast enhancement post-gadolinium (gadopentetate dimeglumine, Gd-DTPA) in control mouse brain and mice with ODs suggested that DMSO was fully able to cross the intact blood-brain barrier in both normal brain parenchyma and in low-grade tumors. Our results indicate a potential role for DMSO as a contrast agent for brain tumor detection, even in those tumors 'invisible' to standard gadolinium-enhanced MRI, and possibly for monitoring heterogeneities associated with progression or with therapeutic response. Copyright © 2012 John Wiley & Sons, Ltd.

The neurobiology of psychopathy.

PubMed

Glenn, Andrea L; Raine, Adrian

2008-09-01

Numerous studies have tackled the complex challenge of understanding the neural substrates of psychopathy, revealing that brain abnormalities exist on several levels and in several structures. As we discover more about complex neural networks, it becomes increasingly difficult to clarify how these systems interact with each other to produce the distinct pattern of behavioral and personality characteristics observed in psychopathy. The authors review the recent research on the neurobiology of psychopathy, beginning with molecular neuroscience work and progressing to the level of brain structures and their connectivity. Potential factors that may affect the development of brain impairments, as well as how some systems may be targeted for potential treatment, are discussed.

Trends in brain oxygenation during mental and physical exercise measured using near-infrared spectroscopy (NIRS): potential for early detection of Alzheimer's disease

NASA Astrophysics Data System (ADS)

Allen, Monica S.; Allen, Jeffery W.; Mikkilineni, Shweta; Liu, Hanli

2005-04-01

Motivation: Early diagnosis of Alzheimer's disease (AD) is crucial because symptoms respond best to available treatments in the initial stages of the disease. Recent studies have shown that marked changes in brain oxygenation during mental and physical tasks can be used for noninvasive functional brain imaging to detect Alzheimer"s disease. The goal of our study is to explore the possibility of using near infrared spectroscopy (NIRS) and mapping (NIRM) as a diagnostic tool for AD before the onset of significant morphological changes in the brain. Methods: A 16-channel NIRS brain imager was used to noninvasively measure spatial and temporal changes in cerebral hemodynamics induced during verbal fluency task and physical activity. The experiments involved healthy subjects (n = 10) in the age range of 25+/-5 years. The NIRS signals were taken from the subjects' prefrontal cortex during the activities. Results and Conclusion: Trends of oxygenated and deoxygenated hemoglobin in the prefrontal cortex of the brain were observed. During the mental stimulation, the subjects showed significant increase in oxygenated hemoglobin [HbO2] with a simultaneous decrease in deoxygenated hemoglobin [Hb]. However, physical exercise caused a rise in levels of HbO2 with small variations in Hb. This study basically demonstrates that NIRM taken from the prefrontal cortex of the human brain is sensitive to both mental and physical tasks and holds potential to serve as a diagnostic means for early detection of Alzheimer's disease.

Nose-to-brain peptide delivery - The potential of nanotechnology.

PubMed

Samaridou, Eleni; Alonso, Maria José

2018-06-01

Nose-to-brain (N-to-B) delivery offers to protein and peptide drugs the possibility to reach the brain in a non-invasive way. This article is a comprehensive review of the state-of-the-art of this emerging peptide delivery route, as well as of the challenges associated to it. Emphasis is given on the potential of nanosized drug delivery carriers to enhance the direct N-to-B transport of protein or peptide drugs. In particular, polymer- and lipid- based nanocarriers are comparatively analyzed in terms of the influence of their physicochemical characteristics and composition on their in vivo fate and efficacy. The use of biorecognitive ligands and permeation enhancers in order to enhance their brain targeting efficiency is also discussed. The article concludes highlighting the early stage of this research field and its still unveiled potential. The final message is that more explicatory PK/PD studies are required in order to achieve the translation from preclinical to the clinical development phase. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clarifying Relations Between Dispositional Aggression and Brain Potential Response: Overlapping and Distinct Contributions of Impulsivity and Stress Reactivity

PubMed Central

Venables, Noah C.; Patrick, Christopher J.; Hall, Jason R.; Bernat, Edward M.

2011-01-01

Impulsive-aggressive individuals exhibit deficits in amplitude of the P3 brain potential response, however, it remains unclear how separable dispositional traits account for this association. The current study sought to clarify the basis of this association by examining contributions of trait impulsiveness and stress reactivity to the observed relationship between dispositional aggression and amplitude of the P3 brain potential response in a visual novelty-oddball procedure. A significant negative association was found between aggressiveness and amplitude of P3 response to both target and novel stimuli over frontal-central scalp sites. Impulsivity showed a parallel inverse relationship with P3 amplitude, attributable to its overlap with dispositional aggression. In contrast, stress reactivity did not exhibit a zero-order association with P3 amplitude, but modestly predicted P3 in a positive direction after accounting for its overlap with aggression. Results are discussed in terms of their implications for individual difference variables and brain processes underlying impulsive-aggressive behavior. PMID:21262318

Therapeutic Potential of Curcumin for the Treatment of Brain Tumors

PubMed Central

Klinger, Neil V.

2016-01-01

Brain malignancies currently carry a poor prognosis despite the current multimodal standard of care that includes surgical resection and adjuvant chemotherapy and radiation. As new therapies are desperately needed, naturally occurring chemical compounds have been studied for their potential chemotherapeutic benefits and low toxicity profile. Curcumin, found in the rhizome of turmeric, has extensive therapeutic promise via its antioxidant, anti-inflammatory, and antiproliferative properties. Preclinical in vitro and in vivo data have shown it to be an effective treatment for brain tumors including glioblastoma multiforme. These effects are potentiated by curcumin's ability to induce G2/M cell cycle arrest, activation of apoptotic pathways, induction of autophagy, disruption of molecular signaling, inhibition of invasion, and metastasis and by increasing the efficacy of existing chemotherapeutics. Further, clinical data suggest that it has low toxicity in humans even at large doses. Curcumin is a promising nutraceutical compound that should be evaluated in clinical trials for the treatment of human brain tumors. PMID:27807473

Neurocognitive mechanisms of mathematical giftedness: A literature review.

PubMed

Zhang, Li; Gan, John Q; Wang, Haixian

2017-01-01

Mathematically gifted children/adolescents have demonstrated exceptional abilities and traits in logical reasoning, mental imagery, and creative thinking. In the field of cognitive neuroscience, the past studies on mathematically gifted brains have concentrated on investigating event-related brain activation regions, cerebral laterality of cognitive functions, functional specialization that is uniquely dedicated for specific cognitive purposes, and functional interactions among discrete brain regions. From structural and functional perspectives, these studies have witnessed both "general" and "unique" neural characteristics of mathematically gifted brains. In this article, the theoretical background, empirical studies, and neurocognitive mechanisms of mathematically gifted children/adolescents are reviewed. Based on the integration of the findings, some potential directions for the future research are identified and discussed.

Neuroimaging Studies Illustrate the Commonalities Between Ageing and Brain Diseases.

PubMed

Cole, James H

2018-07-01

The lack of specificity in neuroimaging studies of neurological and psychiatric diseases suggests that these different diseases have more in common than is generally considered. Potentially, features that are secondary effects of different pathological processes may share common neurobiological underpinnings. Intriguingly, many of these mechanisms are also observed in studies of normal (i.e., non-pathological) brain ageing. Different brain diseases may be causing premature or accelerated ageing to the brain, an idea that is supported by a line of "brain ageing" research that combines neuroimaging data with machine learning analysis. In reviewing this field, I conclude that such observations could have important implications, suggesting that we should shift experimental paradigm: away from characterizing the average case-control brain differences resulting from a disease toward methods that place individuals in their age-appropriate context. This will also lead naturally to clinical applications, whereby neuroimaging can contribute to a personalized-medicine approach to improve brain health. © 2018 WILEY Periodicals, Inc.

Transferrin-appended PEGylated nanoparticles for temozolomide delivery to brain: in vitro characterisation.

PubMed

Jain, Aviral; Chasoo, Gousia; Singh, Shashank K; Saxena, Ajit K; Jain, Sanjay K

2011-01-01

Polymer-based nanotechnologies are proposed to be an alternative for drug administration, delivery and targeting to those of conventional formulations. The blood brain barrier is frequently a rate-limiting factor in determining permeation of a drug into brain. In this study, the surface-engineered long-circulating PLGA nanoparticles (NPs) were assessed for brain-specific delivery. Long circulating NPs of PLGA- and PEG-synthesised copolymer were prepared by emulsification solvent evaporation method. Further, the surface of PEGylated NPs was modified by anchoring transferrin (Tf) ligand for receptor-mediated targeting to brain. NPs were characterised for shape and size, zeta potential, entrapment efficiency and in vitro drug release. In vitro cytotoxicity studies were performed on human cancer cell lines. Confocal Laser Scanning Microscopy studies show the enhanced uptake of Tf-appended PEGylated NPs and their localisation in the brain tissues. Hence, the specific role of Tf ligand on PEGylated NPs for brain delivery was confirmed.

Silicon chip with capacitors and transistors for interfacing organotypic brain slice of rat hippocampus.

PubMed

Hutzler, Michael; Fromherz, Peter

2004-04-01

Probing projections between brain areas and their modulation by synaptic potentiation requires dense arrays of contacts for noninvasive electrical stimulation and recording. Semiconductor technology is able to provide planar arrays with high spatial resolution to be used with planar neuronal structures such as organotypic brain slices. To address basic methodical issues we developed a silicon chip with simple arrays of insulated capacitors and field-effect transistors for stimulation of neuronal activity and recording of evoked field potentials. Brain slices from rat hippocampus were cultured on that substrate. We achieved local stimulation of the CA3 region by applying defined voltage pulses to the chip capacitors. Recording of resulting local field potentials in the CA1 region was accomplished with transistors. The relationship between stimulation and recording was rationalized by a sheet conductor model. By combining a row of capacitors with a row of transistors we determined a simple stimulus-response matrix from CA3 to CA1. Possible contributions of inhomogeneities of synaptic projection, of tissue structure and of neuroelectronic interfacing were considered. The study provides the basis for a development of semiconductor chips with high spatial resolution that are required for long-term studies of topographic mapping.

Down syndrome's brain dynamics: analysis of fractality in resting state.

PubMed

Hemmati, Sahel; Ahmadlou, Mehran; Gharib, Masoud; Vameghi, Roshanak; Sajedi, Firoozeh

2013-08-01

To the best knowledge of the authors there is no study on nonlinear brain dynamics of down syndrome (DS) patients, whereas brain is a highly complex and nonlinear system. In this study, fractal dimension of EEG, as a key characteristic of brain dynamics, showing irregularity and complexity of brain dynamics, was used for evaluation of the dynamical changes in the DS brain. The results showed higher fractality of the DS brain in almost all regions compared to the normal brain, which indicates less centrality and higher irregular or random functioning of the DS brain regions. Also, laterality analysis of the frontal lobe showed that the normal brain had a right frontal laterality of complexity whereas the DS brain had an inverse pattern (left frontal laterality). Furthermore, the high accuracy of 95.8 % obtained by enhanced probabilistic neural network classifier showed the potential of nonlinear dynamic analysis of the brain for diagnosis of DS patients. Moreover, the results showed that the higher EEG fractality in DS is associated with the higher fractality in the low frequencies (delta and theta), in broad regions of the brain, and the high frequencies (beta and gamma), majorly in the frontal regions.

Preservation of mitochondrial functional integrity in mitochondria isolated from small cryopreserved mouse brain areas.

PubMed

Valenti, Daniela; de Bari, Lidia; De Filippis, Bianca; Ricceri, Laura; Vacca, Rosa Anna

2014-01-01

Studies of mitochondrial bioenergetics in brain pathophysiology are often precluded by the need to isolate mitochondria immediately after tissue dissection from a large number of brain biopsies for comparative studies. Here we present a procedure of cryopreservation of small brain areas from which mitochondrial enriched fractions (crude mitochondria) with high oxidative phosphorylation efficiency can be isolated. Small mouse brain areas were frozen and stored in a solution containing glycerol as cryoprotectant. Crude mitochondria were isolated by differential centrifugation from both cryopreserved and freshly explanted brain samples and were compared with respect to their ability to generate membrane potential and produce ATP. Intactness of outer and inner mitochondrial membranes was verified by polarographic ascorbate and cytochrome c tests and spectrophotometric assay of citrate synthase activity. Preservation of structural integrity and oxidative phosphorylation efficiency was successfully obtained in crude mitochondria isolated from different areas of cryopreserved mouse brain samples. Long-term cryopreservation of small brain areas from which intact and phosphorylating mitochondria can be isolated for the study of mitochondrial bioenergetics will significantly expand the study of mitochondrial defects in neurological pathologies, allowing large comparative studies and favoring interlaboratory and interdisciplinary analyses. Copyright © 2013 Elsevier Inc. All rights reserved.

Caffeine intake increases plasma ketones: an acute metabolic study in humans.

PubMed

Vandenberghe, Camille; St-Pierre, Valérie; Courchesne-Loyer, Alexandre; Hennebelle, Marie; Castellano, Christian-Alexandre; Cunnane, Stephen C

2017-04-01

Brain glucose uptake declines during aging and is significantly impaired in Alzheimer's disease. Ketones are the main alternative brain fuel to glucose so they represent a potential approach to compensate for the brain glucose reduction. Caffeine is of interest as a potential ketogenic agent owing to its actions on lipolysis and lipid oxidation but whether it is ketogenic in humans is unknown. This study aimed to evaluate the acute ketogenic effect of 2 doses of caffeine (2.5; 5.0 mg/kg) in 10 healthy adults. Caffeine given at breakfast significantly stimulated ketone production in a dose-dependent manner (+88%; +116%) and also raised plasma free fatty acids. Whether caffeine has long-term ketogenic effects or could enhance the ketogenic effect of medium chain triglycerides remains to be determined.

A new method for registration of kinesthetic evoked potentials for studies of proprioceptive sensitivity in normal subjects and patients with organic lesions in the brain.

PubMed

Gordeev, S A; Voronin, S G

2015-01-01

The proprioceptive sensitivity of healthy volunteers and convalescents after acute cerebrovascular episodes was studied by a new neurophysiological method for registration of kinesthetic evoked potentials emerging in response to passive 50(o) bending of the hand in the wrist joint with the angular acceleration of 350 rad/sec(2). Kinesthetic evoked potentials were recorded above the somatosensory cortex projection areas in the hemispheres contra- and ipsilateral to the stimulated limb. The patients exhibited significantly longer latencies and lesser amplitudes of the early components of response in the involved hemisphere in comparison with normal subjects. The method for registration of the kinesthetic evoked potentials allows a more detailed study of the mechanisms of kinesthetic sensitivity in health and in organic involvement of the brain.

Therapeutic Potential of Intravenous Immunoglobulin in Acute Brain Injury

PubMed Central

Thom, Vivien; Arumugam, Thiruma V.; Magnus, Tim; Gelderblom, Mathias

2017-01-01

Acute ischemic and traumatic injury of the central nervous system (CNS) is known to induce a cascade of inflammatory events that lead to secondary tissue damage. In particular, the sterile inflammatory response in stroke has been intensively investigated in the last decade, and numerous experimental studies demonstrated the neuroprotective potential of a targeted modulation of the immune system. Among the investigated immunomodulatory agents, intravenous immunoglobulin (IVIg) stand out due to their beneficial therapeutic potential in experimental stroke as well as several other experimental models of acute brain injuries, which are characterized by a rapidly evolving sterile inflammatory response, e.g., trauma, subarachnoid hemorrhage. IVIg are therapeutic preparations of polyclonal immunoglobulin G, extracted from the plasma of thousands of donors. In clinical practice, IVIg are the treatment of choice for diverse autoimmune diseases and various mechanisms of action have been proposed. Only recently, several experimental studies implicated a therapeutic potential of IVIg even in models of acute CNS injury, and suggested that the immune system as well as neuronal cells can directly be targeted by IVIg. This review gives further insight into the role of secondary inflammation in acute brain injury with an emphasis on stroke and investigates the therapeutic potential of IVIg. PMID:28824617

Towards the utilization of EEG as a brain imaging tool.

PubMed

Michel, Christoph M; Murray, Micah M

2012-06-01

Recent advances in signal analysis have engendered EEG with the status of a true brain mapping and brain imaging method capable of providing spatio-temporal information regarding brain (dys)function. Because of the increasing interest in the temporal dynamics of brain networks, and because of the straightforward compatibility of the EEG with other brain imaging techniques, EEG is increasingly used in the neuroimaging community. However, the full capability of EEG is highly underestimated. Many combined EEG-fMRI studies use the EEG only as a spike-counter or an oscilloscope. Many cognitive and clinical EEG studies use the EEG still in its traditional way and analyze grapho-elements at certain electrodes and latencies. We here show that this way of using the EEG is not only dangerous because it leads to misinterpretations, but it is also largely ignoring the spatial aspects of the signals. In fact, EEG primarily measures the electric potential field at the scalp surface in the same way as MEG measures the magnetic field. By properly sampling and correctly analyzing this electric field, EEG can provide reliable information about the neuronal activity in the brain and the temporal dynamics of this activity in the millisecond range. This review explains some of these analysis methods and illustrates their potential in clinical and experimental applications. Copyright © 2011 Elsevier Inc. All rights reserved.

Efficacy of brain-computer interface-driven neuromuscular electrical stimulation for chronic paresis after stroke.

PubMed

Mukaino, Masahiko; Ono, Takashi; Shindo, Keiichiro; Fujiwara, Toshiyuki; Ota, Tetsuo; Kimura, Akio; Liu, Meigen; Ushiba, Junichi

2014-04-01

Brain computer interface technology is of great interest to researchers as a potential therapeutic measure for people with severe neurological disorders. The aim of this study was to examine the efficacy of brain computer interface, by comparing conventional neuromuscular electrical stimulation and brain computer interface-driven neuromuscular electrical stimulation, using an A-B-A-B withdrawal single-subject design. A 38-year-old male with severe hemiplegia due to a putaminal haemorrhage participated in this study. The design involved 2 epochs. In epoch A, the patient attempted to open his fingers during the application of neuromuscular electrical stimulation, irrespective of his actual brain activity. In epoch B, neuromuscular electrical stimulation was applied only when a significant motor-related cortical potential was observed in the electroencephalogram. The subject initially showed diffuse functional magnetic resonance imaging activation and small electro-encephalogram responses while attempting finger movement. Epoch A was associated with few neurological or clinical signs of improvement. Epoch B, with a brain computer interface, was associated with marked lateralization of electroencephalogram (EEG) and blood oxygenation level dependent responses. Voluntary electromyogram (EMG) activity, with significant EEG-EMG coherence, was also prompted. Clinical improvement in upper-extremity function and muscle tone was observed. These results indicate that self-directed training with a brain computer interface may induce activity- dependent cortical plasticity and promote functional recovery. This preliminary clinical investigation encourages further research using a controlled design.

Maternal adiposity negatively influences infant brain white matter development

USDA-ARS?s Scientific Manuscript database

Objective: To study potential effects of maternal body composition on central nervous system (CNS) development of newborn infants. Methods: Diffusion tensor imaging was used to evaluate brain white matter development in 2-week-old, full-term, appropriate for gestational age infants from uncomplicat...

Brain functional magnetic resonance imaging response to glucose and fructose infusions in humans

USDA-ARS?s Scientific Manuscript database

Objective: In animals, intracerebroventricular glucose and fructose have opposing effects on appetite and weight regulation. In humans, functional brain magnetic resonance imaging (fMRI) studies during carbohydrate ingestion suggest that glucose may regulate HT signaling but are potentially confoun...

In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences

PubMed Central

Zhu, Xiao-Hong; Lu, Ming; Lee, Byeong-Yeul; Ugurbil, Kamil; Chen, Wei

2015-01-01

NAD is an essential metabolite that exists in NAD+ or NADH form in all living cells. Despite its critical roles in regulating mitochondrial energy production through the NAD+/NADH redox state and modulating cellular signaling processes through the activity of the NAD+-dependent enzymes, the method for quantifying intracellular NAD contents and redox state is limited to a few in vitro or ex vivo assays, which are not suitable for studying a living brain or organ. Here, we present a magnetic resonance (MR) -based in vivo NAD assay that uses the high-field MR scanner and is capable of noninvasively assessing NAD+ and NADH contents and the NAD+/NADH redox state in intact human brain. The results of this study provide the first insight, to our knowledge, into the cellular NAD concentrations and redox state in the brains of healthy volunteers. Furthermore, an age-dependent increase of intracellular NADH and age-dependent reductions in NAD+, total NAD contents, and NAD+/NADH redox potential of the healthy human brain were revealed in this study. The overall findings not only provide direct evidence of declined mitochondrial functions and altered NAD homeostasis that accompany the normal aging process but also, elucidate the merits and potentials of this new NAD assay for noninvasively studying the intracellular NAD metabolism and redox state in normal and diseased human brain or other organs in situ. PMID:25730862

Practical Designs of Brain-Computer Interfaces Based on the Modulation of EEG Rhythms

NASA Astrophysics Data System (ADS)

Wang, Yijun; Gao, Xiaorong; Hong, Bo; Gao, Shangkai

A brain-computer interface (BCI) is a communication channel which does not depend on the brain's normal output pathways of peripheral nerves and muscles [1-3]. It supplies paralyzed patients with a new approach to communicate with the environment. Among various brain monitoring methods employed in current BCI research, electroencephalogram (EEG) is the main interest due to its advantages of low cost, convenient operation and non-invasiveness. In present-day EEG-based BCIs, the following signals have been paid much attention: visual evoked potential (VEP), sensorimotor mu/beta rhythms, P300 evoked potential, slow cortical potential (SCP), and movement-related cortical potential (MRCP). Details about these signals can be found in chapter "Brain Signals for Brain-Computer Interfaces". These systems offer some practical solutions (e.g., cursor movement and word processing) for patients with motor disabilities.

Blood biomarkers for brain injury: What are we measuring?

PubMed Central

Kawata, Keisuke; Liu, Charles Y.; Merkel, Steven F.; Ramirez, Servio H.; Tierney, Ryan T.; Langford, Dianne

2016-01-01

Accurate diagnosis for mild traumatic brain injury (mTBI) remains challenging, as prognosis and return-to-play/work decisions are based largely on patient reports. Numerous investigations have identified and characterized cellular factors in the blood as potential biomarkers for TBI, in the hope that these factors may be used to gauge the severity of brain injury. None of these potential biomarkers have advanced to use in the clinical setting. Some of the most extensively studied blood biomarkers for TBI include S100β, neuron-specific enolase, glial fibrillary acidic protein, and Tau. Understanding the biological function of each of these factors may be imperative to achieve progress in the field. We address the basic question: what are we measuring? This review will discuss blood biomarkers in terms of cellular origin, normal and pathological function, and possible reasons for increased blood levels. Considerations in the selection, evaluation, and validation of potential biomarkers will also be addressed, along with mechanisms that allow brain-derived proteins to enter the bloodstream after TBI. Lastly, we will highlight perspectives and implications for repetitive neurotrauma in the field of blood biomarkers for brain injury. PMID:27181909

Counter striking psychosis: Commercial video games as potential treatment in schizophrenia? A systematic review of neuroimaging studies.

PubMed

Suenderhauf, Claudia; Walter, Anna; Lenz, Claudia; Lang, Undine E; Borgwardt, Stefan

2016-09-01

Schizophrenia is a severe, chronic, and strongly disabling neuropsychiatric disorder, characterized by cognitive decline, positive and negative symptoms. Positive symptoms respond well to antipsychotic medication and psycho-social interventions, in contrast to negative symptoms and neurocognitive impairments. Cognitive deficits have been linked to a poorer outcome and hence specific cognitive remediation therapies have been proposed. Their effectiveness is nowadays approved and neurobiological correlates have been reconfirmed by brain imaging studies. Interestingly, recent MRI work showed that commercial video games modified similar brain areas as these specialized training programs. If gray matter increases and functional brain modulations would translate in better cognitive and every day functioning, commercial video game training could be an enjoyable and economically interesting treatment option for patients with neuropsychiatric disorders. This systematic review summarizes advances in the area with emphasis on imaging studies dealing with brain changes upon video game training and contrasts them to conventional cognitive remediation. Moreover, we discuss potential challenges therapeutic video game development and research would have to face in future treatment of schizophrenia. Copyright © 2016. Published by Elsevier Ltd.

Characterizing and Modulating Brain Circuitry through Transcranial Magnetic Stimulation Combined with Electroencephalography.

PubMed

Farzan, Faranak; Vernet, Marine; Shafi, Mouhsin M D; Rotenberg, Alexander; Daskalakis, Zafiris J; Pascual-Leone, Alvaro

2016-01-01

The concurrent combination of transcranial magnetic stimulation (TMS) with electroencephalography (TMS-EEG) is a powerful technology for characterizing and modulating brain networks across developmental, behavioral, and disease states. Given the global initiatives in mapping the human brain, recognition of the utility of this technique is growing across neuroscience disciplines. Importantly, TMS-EEG offers translational biomarkers that can be applied in health and disease, across the lifespan, and in humans and animals, bridging the gap between animal models and human studies. However, to utilize the full potential of TMS-EEG methodology, standardization of TMS-EEG study protocols is needed. In this article, we review the principles of TMS-EEG methodology, factors impacting TMS-EEG outcome measures, and the techniques for preventing and correcting artifacts in TMS-EEG data. To promote the standardization of this technique, we provide comprehensive guides for designing TMS-EEG studies and conducting TMS-EEG experiments. We conclude by reviewing the application of TMS-EEG in basic, cognitive and clinical neurosciences, and evaluate the potential of this emerging technology in brain research.

Characterizing and Modulating Brain Circuitry through Transcranial Magnetic Stimulation Combined with Electroencephalography

PubMed Central

Farzan, Faranak; Vernet, Marine; Shafi, Mouhsin M. D.; Rotenberg, Alexander; Daskalakis, Zafiris J.; Pascual-Leone, Alvaro

2016-01-01

The concurrent combination of transcranial magnetic stimulation (TMS) with electroencephalography (TMS-EEG) is a powerful technology for characterizing and modulating brain networks across developmental, behavioral, and disease states. Given the global initiatives in mapping the human brain, recognition of the utility of this technique is growing across neuroscience disciplines. Importantly, TMS-EEG offers translational biomarkers that can be applied in health and disease, across the lifespan, and in humans and animals, bridging the gap between animal models and human studies. However, to utilize the full potential of TMS-EEG methodology, standardization of TMS-EEG study protocols is needed. In this article, we review the principles of TMS-EEG methodology, factors impacting TMS-EEG outcome measures, and the techniques for preventing and correcting artifacts in TMS-EEG data. To promote the standardization of this technique, we provide comprehensive guides for designing TMS-EEG studies and conducting TMS-EEG experiments. We conclude by reviewing the application of TMS-EEG in basic, cognitive and clinical neurosciences, and evaluate the potential of this emerging technology in brain research. PMID:27713691

Modulation of Cholinergic Pathways and Inflammatory Mediators in Blast-Induced Traumatic Brain Injury

DTIC Science & Technology

2013-01-01

matic brain injury (TBI). Centrally acting acetylcholinesterase (AChE) inhibitors are also being considered as potential therapeutic candidates...repeated blast exposures [12]. AChE inhibitors are possible therapeutic candidates against Alzheimer’s disease and TBI [13–15]. In this study, we...esterase inhibitor , as described earlier [12,17–19]. Brain AChE activity was expressed as milliunits/mg protein. 2.3. Microarray analysis Various

Transcriptomic configuration of mouse brain induced by adolescent exposure to 3,4-methylenedioxymethamphetamine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eun, Jung Woo; Kwack, Seung Jun; Noh, Ji Heon

The amphetamine derivative ({+-})-3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a synthetic amphetamine analogue used recreationally to obtain an enhanced affiliative emotional response. MDMA is a potent monoaminergic neurotoxin with the potential to damage brain serotonin and/or dopamine neurons. As the majority of MDMA users are young adults, the risk that users may expose the fetus to MDMA is a concern. However, the majority of studies on MDMA have investigated the effects on adult animals. Here, we investigated whether long-term exposure to MDMA, especially in adolescence, could induce comprehensive transcriptional changes in mouse brain. Transcriptomic analysis of mouse brain regions demonstrated significantmore » gene expression changes in the cerebral cortex. Supervised analysis identified 1028 genes that were chronically dysregulated by long-term exposure to MDMA in adolescent mice. Functional categories most represented by this MDMA characteristic signature are intracellular molecular signaling pathways of neurotoxicity, such as, the MAPK signaling pathway, the Wnt signaling pathway, neuroactive ligand-receptor interaction, long-term potentiation, and the long-term depression signaling pathway. Although these resultant large-scale molecular changes remain to be studied associated with functional brain damage caused by MDMA, our observations delineate the possible neurotoxic effects of MDMA on brain function, and have therapeutic implications concerning neuro-pathological conditions associated with MDMA abuse.« less

Preventable and Potentially Preventable Traumatic Death Rates in Neurosurgery Department: A Single Center Experience.

PubMed

Ha, Mahnjeong; Kim, Byung Chul; Choi, Seonuoo; Cho, Won Ho; Choi, Hyuk Jin

2016-10-01

Preventable and potentially preventable traumatic death rates is a method to evaluate the preventability of the traumatic deaths in emergency medical department. To evaluate the preventability of the traumatic deaths in patients who were admitted to neurosurgery department, we performed this study. A retrospective review identified 52 patients who admitted to neurosurgery department with severe traumatic brain injuries between 2013 and 2014. Based on radiologic and clinical state at emergency room, each preventability of death was estimated by professional panel discussion. And the final death rates were calculated. The preventable and potentially preventable traumatic death rates was 19.2% in this study. This result is lower than that of the research of 2012, Korean preventable and potentially preventable traumatic death rates. The rate of preventable and potentially preventable traumatic death of operation group is lower than that of conservative treatment group. Also, we confirmed that direct transfer and the time to operation are important to reduce the preventability. We report the preventable and potentially preventable traumatic death rates of our institute for evaluation of preventability in severe traumatic brain injuries during the last 2 years. For decrease of preventable death, we suggest that continuous survey of the death rate of traumatic brain injury patients is required.

Preventable and Potentially Preventable Traumatic Death Rates in Neurosurgery Department: A Single Center Experience

PubMed Central

Ha, Mahnjeong; Kim, Byung Chul; Choi, Seonuoo; Cho, Won Ho

2016-01-01

Objective Preventable and potentially preventable traumatic death rates is a method to evaluate the preventability of the traumatic deaths in emergency medical department. To evaluate the preventability of the traumatic deaths in patients who were admitted to neurosurgery department, we performed this study. Methods A retrospective review identified 52 patients who admitted to neurosurgery department with severe traumatic brain injuries between 2013 and 2014. Based on radiologic and clinical state at emergency room, each preventability of death was estimated by professional panel discussion. And the final death rates were calculated. Results The preventable and potentially preventable traumatic death rates was 19.2% in this study. This result is lower than that of the research of 2012, Korean preventable and potentially preventable traumatic death rates. The rate of preventable and potentially preventable traumatic death of operation group is lower than that of conservative treatment group. Also, we confirmed that direct transfer and the time to operation are important to reduce the preventability. Conclusion We report the preventable and potentially preventable traumatic death rates of our institute for evaluation of preventability in severe traumatic brain injuries during the last 2 years. For decrease of preventable death, we suggest that continuous survey of the death rate of traumatic brain injury patients is required. PMID:27857910

Law, Responsibility, and the Brain

NASA Astrophysics Data System (ADS)

Mobbs, Dean; Lau, Hakwan C.; Jones, Owen D.; Frith, Chris D.

In perhaps the first attempt to link the brain to mental illness, Hippocrates elegantly wrote that it is the brain that makes us mad or delirious. Epitomizing one of the fundamental assumptions of contemporary neuroscience, Hippocrates' words resonate far beyond the classic philosophical puzzle of mind and body and posit that our behavior, no matter how monstrous, lies at the mercy of our brain's integrity. While clinicopathological observations have long pointed to several putative neurobiological systems as important in antisocial and violent criminal behavior, recent advances in brain-imaging have the potential to provide unparalleled insight. Consequently, brain-imaging studies have reinvigorated the neurophilosophical and legal debate of whether we are free agents in control of our own actions or mere prisoners of a biologically determined brain. In this chapter, we review studies pointing to brain dysfunction in criminally violent individuals and address a range of philosophical and practical issues concerning the use of brainimaging in court. We finally lay out several guidelines for its use in the legal system.

Differences between brain mass and body weight scaling to height: potential mechanism of reduced mass-specific resting energy expenditure of taller adults.

PubMed

Heymsfield, Steven B; Chirachariyavej, Thamrong; Rhyu, Im Joo; Roongpisuthipong, Chulaporn; Heo, Moonseong; Pietrobelli, Angelo

2009-01-01

Adult resting energy expenditure (REE) scales as height( approximately 1.5), whereas body weight (BW) scales as height( approximately 2). Mass-specific REE (i.e., REE/BW) is thus lower in tall subjects compared with their shorter counterparts, the mechanism of which is unknown. We evaluated the hypothesis that high-metabolic-rate brain mass scales to height with a power significantly less than that of BW, a theory that if valid would provide a potential mechanism for height-related REE effects. The hypothesis was tested by measuring brain mass on a large (n = 372) postmortem sample of Thai men. Since brain mass-body size relations may be influenced by age, the hypothesis was secondarily explored in Thai men age < or =45 yr (n = 299) and with brain magnetic resonance imaging (MRI) studies in Korean men (n = 30) age > or =20<30 yr. The scaling of large body compartments was examined in a third group of Asian men living in New York (NY, n = 28) with MRI and dual-energy X-ray absorptiometry. Brain mass scaled to height with a power (mean +/- SEE; 0.46 +/- 0.13) significantly smaller (P < 0.001) than that of BW scaled to height (2.36 +/- 0.19) in the whole group of Thai men; brain mass/BW scaled negatively to height (-1.94 +/- 0.20, P < 0.001). Similar results were observed in younger Thai men, and results for brain mass/BW vs. height were directionally the same (P = 0.09) in Korean men. Skeletal muscle and bone scaled to height with powers similar to that of BW (i.e., approximately 2-3) in the NY Asian men. Models developed using REE estimates in Thai men suggest that brain accounts for most of the REE/BW height dependency. Tall and short men thus differ in relative brain mass, but the proportions of BW as large compartments appear independent of height, observations that provide a potential mechanistic basis for related differences in REE and that have implications for the study of adult energy requirements.

In vivo evaluation of 18F-MNI698: an 18F-labeled radiotracer for imaging of serotonin 4 receptors in brain.

PubMed

Tavares, Adriana Alexandre S; Caillé, Fabien; Barret, Olivier; Papin, Caroline; Lee, Hsiaoju; Morley, Thomas J; Fowles, Krista; Holden, Daniel; Seibyl, John P; Alagille, David; Tamagnan, Gilles D

2014-05-01

Serotonin 4 receptors (5-hydroxytryptamine receptor 4 [5HT4R]) hold promise as a novel therapeutic approach to multiple brain disorders, including Alzheimer and Huntington disease. In vivo imaging of these receptors with selective 5HT4R radiotracers and PET would be valuable to investigate alterations in 5HT4R in different brain disorders and to assist drug discovery. In this study, (18)F-MNI698 was evaluated as a potential PET radiotracer for imaging of 5HT4R in the brain. Eighteen PET studies were performed in 3 adult rhesus monkeys. The radiotracer was administered as a bolus intravenous injection or bolus plus constant infusion (time that would be required to inject the bolus at the infusion rate = 60 min), and arterial blood was collected for data quantification. Kinetic models were used to estimate distribution volumes and binding potentials, for which the cerebellum was used as a reference region. (18)F-MNI698 test-retest variability and upper mass dose limits were determined. Preblocking studies using several doses of SB204070, a selective 5HT4R antagonist, were performed. (18)F-MNI698 avidly entered the monkey brain (peak percentage injected dose of ∼ 6.6%), and its brain distribution was consistent with known 5HT4R densities. At 120 min after bolus injection and after the start of radiotracer infusion, only less than 5% and approximately 10% parent compound was present in blood, respectively. Measured binding potentials were underestimated by 22%-36% when noninvasive methods were used for data quantification in comparison with invasive methods. A good agreement was found between test-retest measurements. The radiotracer upper mass dose limit (<5% occupancy) was determined to be 13.1 μg per 70 kg of body weight. SB204070 blocked the radiotracer binding in a dose-dependent manner. Data indicate that (18)F-MNI698 is a promising PET radiotracer for imaging of 5HT4R in the brain, and human studies are warranted based on these study results.

Neuroanatomy of the killer whale (Orcinus orca): a magnetic resonance imaging investigation of structure with insights on function and evolution.

PubMed

Wright, Alexandra; Scadeng, Miriam; Stec, Dominik; Dubowitz, Rebecca; Ridgway, Sam; Leger, Judy St

2017-01-01

The evolutionary process of adaptation to an obligatory aquatic existence dramatically modified cetacean brain structure and function. The brain of the killer whale (Orcinus orca) may be the largest of all taxa supporting a panoply of cognitive, sensory, and sensorimotor abilities. Despite this, examination of the O. orca brain has been limited in scope resulting in significant deficits in knowledge concerning its structure and function. The present study aims to describe the neural organization and potential function of the O. orca brain while linking these traits to potential evolutionary drivers. Magnetic resonance imaging was used for volumetric analysis and three-dimensional reconstruction of an in situ postmortem O. orca brain. Measurements were determined for cortical gray and cerebral white matter, subcortical nuclei, cerebellar gray and white matter, corpus callosum, hippocampi, superior and inferior colliculi, and neuroendocrine structures. With cerebral volume comprising 81.51 % of the total brain volume, this O. orca brain is one of the most corticalized mammalian brains studied to date. O. orca and other delphinoid cetaceans exhibit isometric scaling of cerebral white matter with increasing brain size, a trait that violates an otherwise evolutionarily conserved cerebral scaling law. Using comparative neurobiology, it is argued that the divergent cerebral morphology of delphinoid cetaceans compared to other mammalian taxa may have evolved in response to the sensorimotor demands of the aquatic environment. Furthermore, selective pressures associated with the evolution of echolocation and unihemispheric sleep are implicated in substructure morphology and function. This neuroanatomical dataset, heretofore absent from the literature, provides important quantitative data to test hypotheses regarding brain structure, function, and evolution within Cetacea and across Mammalia.

Inferring deep-brain activity from cortical activity using functional near-infrared spectroscopy

PubMed Central

Liu, Ning; Cui, Xu; Bryant, Daniel M.; Glover, Gary H.; Reiss, Allan L.

2015-01-01

Functional near-infrared spectroscopy (fNIRS) is an increasingly popular technology for studying brain function because it is non-invasive, non-irradiating and relatively inexpensive. Further, fNIRS potentially allows measurement of hemodynamic activity with high temporal resolution (milliseconds) and in naturalistic settings. However, in comparison with other imaging modalities, namely fMRI, fNIRS has a significant drawback: limited sensitivity to hemodynamic changes in deep-brain regions. To overcome this limitation, we developed a computational method to infer deep-brain activity using fNIRS measurements of cortical activity. Using simultaneous fNIRS and fMRI, we measured brain activity in 17 participants as they completed three cognitive tasks. A support vector regression (SVR) learning algorithm was used to predict activity in twelve deep-brain regions using information from surface fNIRS measurements. We compared these predictions against actual fMRI-measured activity using Pearson’s correlation to quantify prediction performance. To provide a benchmark for comparison, we also used fMRI measurements of cortical activity to infer deep-brain activity. When using fMRI-measured activity from the entire cortex, we were able to predict deep-brain activity in the fusiform cortex with an average correlation coefficient of 0.80 and in all deep-brain regions with an average correlation coefficient of 0.67. The top 15% of predictions using fNIRS signal achieved an accuracy of 0.7. To our knowledge, this study is the first to investigate the feasibility of using cortical activity to infer deep-brain activity. This new method has the potential to extend fNIRS applications in cognitive and clinical neuroscience research. PMID:25798327

The anatomical problem posed by brain complexity and size: a potential solution.

PubMed

DeFelipe, Javier

2015-01-01

Over the years the field of neuroanatomy has evolved considerably but unraveling the extraordinary structural and functional complexity of the brain seems to be an unattainable goal, partly due to the fact that it is only possible to obtain an imprecise connection matrix of the brain. The reasons why reaching such a goal appears almost impossible to date is discussed here, together with suggestions of how we could overcome this anatomical problem by establishing new methodologies to study the brain and by promoting interdisciplinary collaboration. Generating a realistic computational model seems to be the solution rather than attempting to fully reconstruct the whole brain or a particular brain region.

Keeping brains young with making music.

PubMed

Rogenmoser, Lars; Kernbach, Julius; Schlaug, Gottfried; Gaser, Christian

2018-01-01

Music-making is a widespread leisure and professional activity that has garnered interest over the years due to its effect on brain and cognitive development and its potential as a rehabilitative and restorative therapy of brain dysfunctions. We investigated whether music-making has a potential age-protecting effect on the brain. For this, we studied anatomical magnetic resonance images obtained from three matched groups of subjects who differed in their lifetime dose of music-making activities (i.e., professional musicians, amateur musicians, and non-musicians). For each subject, we calculated a so-called BrainAGE score which corresponds to the discrepancy (in years) between chronological age and the "age of the brain", with negative values reflecting an age-decelerating brain and positive values an age-accelerating brain, respectively. The index of "brain age" was estimated using a machine-learning algorithm that was trained in a large independent sample to identify anatomical correlates of brain-aging. Compared to non-musicians, musicians overall had lower BrainAGE scores, with amateur musicians having the lowest scores suggesting that music-making has an age-decelerating effect on the brain. Unlike the amateur musicians, the professional musicians showed a positive correlation between their BrainAGE scores and years of music-making, possibly indicating that engaging more intensely in just one otherwise enriching activity might not be as beneficial than if the activity is one of several that an amateur musician engages in. Intense music-making activities at a professional level could also lead to stress-related interferences and a less enriched environment than that of amateur musicians, possibly somewhat diminishing the otherwise positive effect of music-making.

Diet and Gender Influences on Processing and Discrimination of Speech Sounds in 3- and 6-Month-Old Infants: A Developmental ERP Study

ERIC Educational Resources Information Center

Pivik, R. T.; Andres, Aline; Badger, Thomas M.

2011-01-01

Early post-natal nutrition influences later development, but there are no studies comparing brain function in healthy infants as a function of dietary intake even though the major infant diets differ significantly in nutrient composition. We studied brain responses (event-related potentials; ERPs) to speech sounds for infants who were fed either…

Targeted DNA sequencing of non-small cell lung cancer identifies mutations associated with brain metastases.

PubMed

Wilson, George D; Johnson, Matthew D; Ahmed, Samreen; Cardenas, Paola Yumpo; Grills, Inga S; Thibodeau, Bryan J

2018-05-25

This study explores the hypothesis that dominant molecular oncogenes in non-small cell lung cancer (NSCLC) are associated with metastatic spread to the brain. NSCLC patient groups with no evidence of metastasis, with metastatic disease to a non-CNS site, who developed brain metastasis after diagnosis, and patients with simultaneous diagnosis of NSCLC and metastatic brain lesions were studied using targeted sequencing. In patients with brain metastasis versus those without, only 2 variants (one each in BCL6 and NOTHC2) were identified that occurred in ≥ 4 NSCLC of patients with brain metastases but ≤ 1 of the NSCLC samples without brain metastases. At the gene level, 20 genes were found to have unique variants in more than 33% of the patients with brain metastases. When analyzed at the patient level, these 20 genes formed the basis of a predictive test to discriminate those with brain metastasis. Further analysis showed that PI3K/AKT signaling is altered in both the primary and metastases of NSCLC patients with brain lesions. While no single variant was associated with brain metastasis, this study describes a potential gene panel for the identification of patients at risk and implicates PI3K/AKT signaling as a therapeutic target.

Targeted DNA sequencing of non-small cell lung cancer identifies mutations associated with brain metastases

PubMed Central

Wilson, George D.; Johnson, Matthew D.; Ahmed, Samreen; Cardenas, Paola Yumpo; Grills, Inga S.; Thibodeau, Bryan J.

2018-01-01

Introduction This study explores the hypothesis that dominant molecular oncogenes in non-small cell lung cancer (NSCLC) are associated with metastatic spread to the brain. Methods NSCLC patient groups with no evidence of metastasis, with metastatic disease to a non-CNS site, who developed brain metastasis after diagnosis, and patients with simultaneous diagnosis of NSCLC and metastatic brain lesions were studied using targeted sequencing. Results In patients with brain metastasis versus those without, only 2 variants (one each in BCL6 and NOTHC2) were identified that occurred in ≥ 4 NSCLC of patients with brain metastases but ≤ 1 of the NSCLC samples without brain metastases. At the gene level, 20 genes were found to have unique variants in more than 33% of the patients with brain metastases. When analyzed at the patient level, these 20 genes formed the basis of a predictive test to discriminate those with brain metastasis. Further analysis showed that PI3K/AKT signaling is altered in both the primary and metastases of NSCLC patients with brain lesions. Conclusion While no single variant was associated with brain metastasis, this study describes a potential gene panel for the identification of patients at risk and implicates PI3K/AKT signaling as a therapeutic target. PMID:29899834

The Feasibility and Potential Impact of Brain Training Games on Cognitive and Emotional Functioning in Middle-Aged Adults.

PubMed

McLaughlin, Paula M; Curtis, Ashley F; Branscombe-Caird, Laura M; Comrie, Janna K; Murtha, Susan J E

2018-02-01

To investigate whether a commercially available brain training program is feasible to use with a middle-aged population and has a potential impact on cognition and emotional well-being (proof of concept). Fourteen participants (ages 46-55) completed two 6-week training conditions using a crossover (counterbalanced) design: (1) experimental brain training condition and (2) active control "find answers to trivia questions online" condition. A comprehensive neurocognitive battery and a self-report measure of depression and anxiety were administered at baseline (first time point, before training) and after completing each training condition (second time point at 6 weeks, and third time point at 12 weeks). Cognitive composite scores were calculated for participants at each time point. Study completion and protocol adherence demonstrated good feasibility of this brain training protocol in healthy middle-aged adults. Exploratory analyses suggested that brain training was associated with neurocognitive improvements related to executive attention, as well as improvements in mood. Overall, our findings suggest that brain training programs are feasible in middle-aged cohorts. We propose that brain training games may be linked to improvements in executive attention and affect by promoting cognitive self-efficacy in middle-aged adults.

Neuroinflammation and brain atrophy in former NFL players: An in vivo multimodal imaging pilot study.

PubMed

Coughlin, Jennifer M; Wang, Yuchuan; Munro, Cynthia A; Ma, Shuangchao; Yue, Chen; Chen, Shaojie; Airan, Raag; Kim, Pearl K; Adams, Ashley V; Garcia, Cinthya; Higgs, Cecilia; Sair, Haris I; Sawa, Akira; Smith, Gwenn; Lyketsos, Constantine G; Caffo, Brian; Kassiou, Michael; Guilarte, Tomas R; Pomper, Martin G

2015-02-01

There are growing concerns about potential delayed, neuropsychiatric consequences (e.g, cognitive decline, mood or anxiety disorders) of sports-related traumatic brain injury (TBI). Autopsy studies of brains from a limited number of former athletes have described characteristic, pathologic changes of chronic traumatic encephalopathy (CTE) leading to questions about the relationship between these pathologic and the neuropsychiatric disturbances seen in former athletes. Research in this area will depend on in vivo methods that characterize molecular changes in the brain, linking CTE and other sports-related pathologies with delayed emergence of neuropsychiatric symptoms. In this pilot project we studied former National Football League (NFL) players using new neuroimaging techniques and clinical measures of cognitive functioning. We hypothesized that former NFL players would show molecular and structural changes in medial temporal and parietal lobe structures as well as specific cognitive deficits, namely those of verbal learning and memory. We observed a significant increase in binding of [(11)C]DPA-713 to the translocator protein (TSPO), a marker of brain injury and repair, in several brain regions, such as the supramarginal gyrus and right amygdala, in 9 former NFL players compared to 9 age-matched, healthy controls. We also observed significant atrophy of the right hippocampus. Finally, we report that these same former players had varied performance on a test of verbal learning and memory, suggesting that these molecular and pathologic changes may play a role in cognitive decline. These results suggest that localized brain injury and repair, indicated by increased [(11)C]DPA-713 binding to TSPO, may be linked to history of NFL play. [(11)C]DPA-713 PET is a promising new tool that can be used in future study design to examine further the relationship between TSPO expression in brain injury and repair, selective regional brain atrophy, and the potential link to deficits in verbal learning and memory after NFL play. Copyright © 2014 Elsevier Inc. All rights reserved.

Premature infants display increased noxious-evoked neuronal activity in the brain compared to healthy age-matched term-born infants.

PubMed

Slater, Rebeccah; Fabrizi, Lorenzo; Worley, Alan; Meek, Judith; Boyd, Stewart; Fitzgerald, Maria

2010-08-15

This study demonstrates that infants who are born prematurely and who have experienced at least 40days of intensive or special care have increased brain neuronal responses to noxious stimuli compared to healthy newborns at the same postmenstrual age. We have measured evoked potentials generated by noxious clinically-essential heel lances in infants born at term (8 infants; born 37-40weeks) and in infants born prematurely (7 infants; born 24-32weeks) who had reached the same postmenstrual age (mean age at time of heel lance 39.2+/-1.2weeks). These noxious-evoked potentials are clearly distinguishable from shorter latency potentials evoked by non-noxious tactile sensory stimulation. While the shorter latency touch potentials are not dependent on the age of the infant at birth, the noxious-evoked potentials are significantly larger in prematurely-born infants. This enhancement is not associated with specific brain lesions but reflects a functional change in pain processing in the brain that is likely to underlie previously reported changes in pain sensitivity in older ex-preterm children. Our ability to quantify and measure experience-dependent changes in infant cortical pain processing will allow us to develop a more rational approach to pain management in neonatal intensive care. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Lived Experiences of Iranian Nurses Caring for Brain Death Organ Donor Patients: Caring as “Halo of Ambiguity and Doubt”

PubMed Central

Keshtkaran, Zahra; Sharif, Farkhondeh; Navab, Elham; Gholamzadeh, Sakineh

2016-01-01

Background: Brain death is a concept in which its criteria have been expressed as documentations in Harvard Committee of Brain Death. The various perceptions of caregiver nurses for brain death patients may have effect on the chance of converting potential donors into actual organ donors. Objective: The present study has been conducted in order to perceive the experiences of nurses in care-giving to the brain death of organ donor patients. Methods: This qualitative study was carried out by means of Heidegger’s hermeneutic phenomenology. Eight nurses who have been working in ICU were interviewed. The semi-structured interviews were recorded by a tape-recorder and the given texts were transcribed and the analyses were done by Van-Mannen methodology and (thematic) analysis. Results: One of the foremost themes extracted from this study included ‘Halo of ambiguity and doubt’ that comprised of two sub-themes of ‘having unreasonable hope’ and ‘Conservative acceptance of brain death’. The unreasonable hope included lack of trust (uncertainty) in diagnosis and verification of brain death, passing through denial wall, and avoidance from explicit and direct disclosure of brain death in patients’ family. In this investigation, the nurses were involved in a type of ambiguity and doubt in care-giving to the potentially brain death of organ donor patients, which were also evident in their interaction with patients’ family and for this reason, they did not definitely announce the brain death and so far they hoped for treatment of the given patient. Such confusion and hesitance both caused annoyance of nurses and strengthening the denial of patients’ family to be exposed to death. Conclusion: The results of this study reveal the fundamental perceived care-giving of brain death in organ donor patients and led to developing some strategies to improve care-giving and achievement in donation of the given organ and necessity for presentation of educational and supportive services for nurses might become more evident than ever. PMID:26925919

Brain state-dependence of electrically evoked potentials monitored with head-mounted electronics.

PubMed

Richardson, Andrew G; Fetz, Eberhard E

2012-11-01

Inferring changes in brain connectivity is critical to studies of learning-related plasticity and stimulus-induced conditioning of neural circuits. In addition, monitoring spontaneous fluctuations in connectivity can provide insight into information processing during different brain states. Here, we quantified state-dependent connectivity changes throughout the 24-h sleep-wake cycle in freely behaving monkeys. A novel, head-mounted electronic device was used to electrically stimulate at one site and record evoked potentials at other sites. Electrically evoked potentials (EEPs) revealed the connectivity pattern between several cortical sites and the basal forebrain. We quantified state-dependent changes in the EEPs. Cortico-cortical EEP amplitude increased during slow-wave sleep, compared to wakefulness, while basal-cortical EEP amplitude decreased. The results demonstrate the utility of using portable electronics to document state-dependent connectivity changes in freely behaving primates.

Comparison of effectiveness between cork-screw and peg-screw electrodes for transcranial motor evoked potential monitoring using the finite element method.

PubMed

Tomio, Ryosuke; Akiyama, Takenori; Ohira, Takayuki; Yoshida, Kazunari

2016-01-01

Intraoperative monitoring of motor evoked potentials by transcranial electric stimulation is popular in neurosurgery for monitoring motor function preservation. Some authors have reported that the peg-screw electrodes screwed into the skull can more effectively conduct current to the brain compared to subdermal cork-screw electrodes screwed into the skin. The aim of this study was to investigate the influence of electrode design on transcranial motor evoked potential monitoring. We estimated differences in effectiveness between the cork-screw electrode, peg-screw electrode, and cortical electrode to produce electric fields in the brain. We used the finite element method to visualize electric fields in the brain generated by transcranial electric stimulation using realistic three-dimensional head models developed from T1-weighted images. Surfaces from five layers of the head were separated as accurately as possible. We created the "cork-screws model," "1 peg-screw model," "peg-screws model," and "cortical electrode model". Electric fields in the brain radially diffused from the brain surface at a maximum just below the electrodes in coronal sections. The coronal sections and surface views of the brain showed higher electric field distributions under the peg-screw compared to the cork-screw. An extremely high electric field was observed under cortical electrodes. Our main finding was that the intensity of electric fields in the brain are higher in the peg-screw model than the cork-screw model.

Training the Brain: Practical Applications of Neural Plasticity From the Intersection of Cognitive Neuroscience, Developmental Psychology, and Prevention Science

PubMed Central

Bryck, Richard L.; Fisher, Philip A.

2012-01-01

Prior researchers have shown that the brain has a remarkable ability for adapting to environmental changes. The positive effects of such neural plasticity include enhanced functioning in specific cognitive domains and shifts in cortical representation following naturally occurring cases of sensory deprivation; however, maladaptive changes in brain function and development owing to early developmental adversity and stress have also been well documented. Researchers examining enriched rearing environments in animals have revealed the potential for inducing positive brain plasticity effects and have helped to popularize methods for training the brain to reverse early brain deficits or to boost normal cognitive functioning. In this paper, two classes of empirically based methods of brain training in children are reviewed and critiqued: laboratory-based, mental process training paradigms and ecological interventions based upon neurocognitive conceptual models. Given the susceptibility of executive function disruption, special attention is paid to training programs that emphasize executive function enhancement. In addition, a third approach to brain training, aimed at tapping into compensatory processes, is postulated. Study results showing the effectiveness of this strategy in the field of neurorehabilitation and in terms of naturally occurring compensatory processing in human aging lend credence to the potential of this approach. PMID:21787037

Training the brain: practical applications of neural plasticity from the intersection of cognitive neuroscience, developmental psychology, and prevention science.

PubMed

Bryck, Richard L; Fisher, Philip A

2012-01-01

Prior researchers have shown that the brain has a remarkable ability for adapting to environmental changes. The positive effects of such neural plasticity include enhanced functioning in specific cognitive domains and shifts in cortical representation following naturally occurring cases of sensory deprivation; however, maladaptive changes in brain function and development owing to early developmental adversity and stress have also been well documented. Researchers examining enriched rearing environments in animals have revealed the potential for inducing positive brain plasticity effects and have helped to popularize methods for training the brain to reverse early brain deficits or to boost normal cognitive functioning. In this article, two classes of empirically based methods of brain training in children are reviewed and critiqued: laboratory-based, mental process training paradigms and ecological interventions based upon neurocognitive conceptual models. Given the susceptibility of executive function disruption, special attention is paid to training programs that emphasize executive function enhancement. In addition, a third approach to brain training, aimed at tapping into compensatory processes, is postulated. Study results showing the effectiveness of this strategy in the field of neurorehabilitation and in terms of naturally occurring compensatory processing in human aging lend credence to the potential of this approach. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Altered resting-state whole-brain functional networks of neonates with intrauterine growth restriction.

PubMed

Batalle, Dafnis; Muñoz-Moreno, Emma; Tornador, Cristian; Bargallo, Nuria; Deco, Gustavo; Eixarch, Elisenda; Gratacos, Eduard

2016-04-01

The feasibility to use functional MRI (fMRI) during natural sleep to assess low-frequency basal brain activity fluctuations in human neonates has been demonstrated, although its potential to characterise pathologies of prenatal origin has not yet been exploited. In the present study, we used intrauterine growth restriction (IUGR) as a model of altered neurodevelopment due to prenatal condition to show the suitability of brain networks to characterise functional brain organisation at neonatal age. Particularly, we analysed resting-state fMRI signal of 20 neonates with IUGR and 13 controls, obtaining whole-brain functional networks based on correlations of blood oxygen level-dependent (BOLD) signal in 90 grey matter regions of an anatomical atlas (AAL). Characterisation of the networks obtained with graph theoretical features showed increased network infrastructure and raw efficiencies but reduced efficiency after normalisation, demonstrating hyper-connected but sub-optimally organised IUGR functional brain networks. Significant association of network features with neurobehavioral scores was also found. Further assessment of spatiotemporal dynamics displayed alterations into features associated to frontal, cingulate and lingual cortices. These findings show the capacity of functional brain networks to characterise brain reorganisation from an early age, and their potential to develop biomarkers of altered neurodevelopment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Material and physical model for evaluation of deep brain activity contribution to EEG recordings

NASA Astrophysics Data System (ADS)

Ye, Yan; Li, Xiaoping; Wu, Tiecheng; Li, Zhe; Xie, Wenwen

2015-12-01

Deep brain activity is conventionally recorded with surgical implantation of electrodes. During the neurosurgery, brain tissue damage and the consequent side effects to patients are inevitably incurred. In order to eliminate undesired risks, we propose that deep brain activity should be measured using the noninvasive scalp electroencephalography (EEG) technique. However, the deeper the neuronal activity is located, the noisier the corresponding scalp EEG signals are. Thus, the present study aims to evaluate whether deep brain activity could be observed from EEG recordings. In the experiment, a three-layer cylindrical head model was constructed to mimic a human head. A single dipole source (sine wave, 10 Hz, altering amplitudes) was embedded inside the model to simulate neuronal activity. When the dipole source was activated, surface potential was measured via electrodes attached on the top surface of the model and raw data were recorded for signal analysis. Results show that the dipole source activity positioned at 66 mm depth in the model, equivalent to the depth of deep brain structures, is clearly observed from surface potential recordings. Therefore, it is highly possible that deep brain activity could be observed from EEG recordings and deep brain activity could be measured using the noninvasive scalp EEG technique.

Blood-brain barrier shuttle peptides enhance AAV transduction in the brain after systemic administration.

PubMed

Zhang, Xintao; He, Ting; Chai, Zheng; Samulski, R Jude; Li, Chengwen

2018-09-01

The adeno-associated virus (AAV) vector has been used in preclinical and clinical trials of gene therapy for central nervous system (CNS) diseases. One of the biggest challenges of effectively delivering AAV to the brain is to surmount the blood-brain barrier (BBB). Herein, we identified several potential BBB shuttle peptides that significantly enhanced AAV8 transduction in the brain after a systemic administration, the best of which was the THR peptide. The enhancement of AAV8 brain transduction by THR is dose-dependent, and neurons are the primary THR targets. Mechanism studies revealed that THR directly bound to the AAV8 virion, increasing its ability to cross the endothelial cell barrier. Further experiments showed that binding of THR to the AAV virion did not interfere with AAV8 infection biology, and that THR competitively blocked transferrin from binding to AAV8. Taken together, our results demonstrate, for the first time, that BBB shuttle peptides are able to directly interact with AAV and increase the ability of the AAV vectors to cross the BBB for transduction enhancement in the brain. These results will shed important light on the potential applications of BBB shuttle peptides for enhancing brain transduction with systemic administration of AAV vectors. Copyright © 2018 Elsevier Ltd. All rights reserved.

Therapeutic potential of brain-derived neurotrophic factor (BDNF) and a small molecular mimics of BDNF for traumatic brain injury.

PubMed

Wurzelmann, Mary; Romeika, Jennifer; Sun, Dong

2017-01-01

Traumatic brain injury (TBI) is a major health problem worldwide. Following primary mechanical insults, a cascade of secondary injuries often leads to further neural tissue loss. Thus far there is no cure to rescue the damaged neural tissue. Current therapeutic strategies primarily target the secondary injuries focusing on neuroprotection and neuroregeneration. The neurotrophin brain-derived neurotrophic factor (BDNF) has significant effect in both aspects, promoting neuronal survival, synaptic plasticity and neurogenesis. Recently, the flavonoid 7,8-dihydroxyflavone (7,8-DHF), a small TrkB agonist that mimics BDNF function, has shown similar effects as BDNF in promoting neuronal survival and regeneration following TBI. Compared to BDNF, 7,8-DHF has a longer half-life and much smaller molecular size, capable of penetrating the blood-brain barrier, which makes it possible for non-invasive clinical application. In this review, we summarize functions of the BDNF/TrkB signaling pathway and studies examining the potential of BDNF and 7,8-DHF as a therapy for TBI.

Simultaneous recording of eeg and direct current (DC) potential makes it possible to assess functional and metabolic state of nervous tissue.

PubMed

Murik, S E; Shapkin, A G

2004-08-01

It has been proposed to assess functional and metabolic state of the brain nervous tissue in terms of bioelectrical parameters. Simultaneous recording of the DC potential level and total slow electrical activity of the nervous tissue was performed in the object of study by nonpolarizable Ag/AgCl electrodes with a DC amplifier. The functional and metabolic state of the brain was determined in terms of enhancement or reduction in the total slow electrical activity and positive or negative shifts in the DC potential level.

Genomic characterization of brain metastases reveals branched evolution and potential therapeutic targets

PubMed Central

Santagata, Sandro; Cahill, Daniel P.; Taylor-Weiner, Amaro; Jones, Robert T.; Van Allen, Eliezer M.; Lawrence, Michael S.; Horowitz, Peleg M.; Cibulskis, Kristian; Ligon, Keith L.; Tabernero, Josep; Seoane, Joan; Martinez-Saez, Elena; Curry, William T.; Dunn, Ian F.; Paek, Sun Ha; Park, Sung-Hye; McKenna, Aaron; Chevalier, Aaron; Rosenberg, Mara; Barker, Frederick G.; Gill, Corey M.; Van Hummelen, Paul; Thorner, Aaron R.; Johnson, Bruce E.; Hoang, Mai P.; Choueiri, Toni K.; Signoretti, Sabina; Sougnez, Carrie; Rabin, Michael S.; Lin, Nancy U.; Winer, Eric P.; Stemmer-Rachamimov, Anat; Meyerson, Matthew; Garraway, Levi; Gabriel, Stacey; Lander, Eric S.; Beroukhim, Rameen; Batchelor, Tracy T.; Baselga, Jose; Louis, David N.

2016-01-01

Brain metastases are associated with a dismal prognosis. Whether brain metastases harbor distinct genetic alterations beyond those observed in primary tumors is unknown. We performed whole-exome sequencing of 86 matched brain metastases, primary tumors and normal tissue. In all clonally related cancer samples, we observed branched evolution, where all metastatic and primary sites shared a common ancestor yet continued to evolve independently. In 53% of cases, we found potentially clinically informative alterations in the brain metastases not detected in the matched primary-tumor sample. In contrast, spatially and temporally separated brain metastasis sites were genetically homogenous. Distal extracranial and regional lymph node metastases were highly divergent from brain metastases. We detected alterations associated with sensitivity to PI3K/AKT/mTOR, CDK, and HER2/EGFR inhibitors in the brain metastases. Genomic analysis of brain metastases provides an opportunity to identify potentially clinically informative alterations not detected in clinically sampled primary tumors, regional lymph nodes, or extracranial metastases. PMID:26410082

EARLY VERSUS LATE MRI IN ASPHYXIATED NEWBORNS TREATED WITH HYPOTHERMIA

PubMed Central

Wintermark, Pia; Hansen, Anne; Soul, Janet; Labrecque, Michelle; Robertson, Richard L.; Warfield, Simon K.

2012-01-01

Objective The purposes of this feasibility study are to assess: (1) the potential utility of early brain magnetic resonance imaging (MRI) in asphyxiated newborns treated with hypothermia; (2) whether early MRI predicts later brain injury observed in these newborns after hypothermia is completed; and (3) whether early MRI indicators of brain injury in these newborns represent reversible changes. Patients and Methods All consecutive asphyxiated term newborns meeting the criteria for therapeutic hypothermia were enrolled prospectively. Each of them underwent 1–2 “early” MRI scans while receiving hypothermia, on day of life (DOL) 1 and DOL 2–3, and also 1–2 “late” MRI scans on DOL 8–13 and at 1 month of age. Results Thirty-seven MRI scans were obtained in twelve asphyxiated neonates treated with induced hypothermia. Four newborns did develop MRI evidence of brain injury, already visible on early MRI scans. The remaining eight newborns did not develop significant MRI evidence of brain injury on any of the MRI scans. In addition, two patients displayed unexpected findings on early MRIs, leading to early termination of hypothermia treatment. Conclusions MRI scans obtained on DOL 2–3 during hypothermia seem to predict later brain injuries in asphyxiated newborns in this feasibility study. Brain injuries identified during this early time appear to represent irreversible changes. Early MRI scans might also be useful to demonstrate unexpected findings not related to hypoxic-ischemic encephalopathy, which could potentially be exacerbated by induced hypothermia. Additional studies with larger numbers of patients will be useful to more definitively confirm these results. PMID:20688865

Inhibition of β2-adrenergic receptor reduces triple-negative breast cancer brain metastases: The potential benefit of perioperative β-blockade.

PubMed

Choy, Cecilia; Raytis, John L; Smith, David D; Duenas, Matthew; Neman, Josh; Jandial, Rahul; Lew, Michael W

2016-06-01

In response to recent studies, we investigated an association between perioperative β-blockade and breast cancer metastases. First, a retrospective study examining perioperative β-blocker use and cancer recurrence and metastases was conducted on 1,029 patients who underwent breast cancer surgery at the City of Hope Cancer Center between 2000 and 2010. We followed the clinical study and examined proliferation, migration, and invasion in vitro of primary and brain-metastatic breast cancer cells in response to β2-activation and inhibition. We also investigated in vivo the metastatic potential of propranolol-treated metastatic cells. For stage II breast cancer patients, perioperative β-blockade was associated with decreased cancer recurrence using Cox regression analysis (hazard's ratio =0.51; 95% CI: 0.23-0.97; p=0.041). Triple-negative (TN) brain-metastatic cells were found to have increased β2-adrenergic receptor mRNA and protein expression relative to TN primary cells. In response to β2-adrenergic receptor activation, TN brain-metastatic cells also exhibited increased cell proliferation and migration relative to the control. These effects were abrogated by propranolol. Propranolol decreased β2-adrenergic receptor-activated invasion. In vivo, propranolol treatment of TN brain-metastatic cells decreased establishment of brain metastases. Our results suggest that stress and corresponding β2-activation may promote the establishment of brain metastases of TN breast cancer cells. In addition, our data suggest a benefit to perioperative β-blockade during surgery-induced stress with respect to breast cancer recurrence and metastases.

Inhibition of β2-adrenergic receptor reduces triple-negative breast cancer brain metastases: The potential benefit of perioperative β-blockade

PubMed Central

CHOY, CECILIA; RAYTIS, JOHN L.; SMITH, DAVID D.; DUENAS, MATTHEW; NEMAN, JOSH; JANDIAL, RAHUL; LEW, MICHAEL W.

2016-01-01

In response to recent studies, we investigated an association between perioperative β-blockade and breast cancer metastases. First, a retrospective study examining perioperative β-blocker use and cancer recurrence and metastases was conducted on 1,029 patients who underwent breast cancer surgery at the City of Hope Cancer Center between 2000 and 2010. We followed the clinical study and examined proliferation, migration, and invasion in vitro of primary and brain-metastatic breast cancer cells in response to β2-activation and inhibition. We also investigated in vivo the metastatic potential of propranolol-treated metastatic cells. For stage II breast cancer patients, perioperative β-blockade was associated with decreased cancer recurrence using Cox regression analysis (hazard's ratio =0.51; 95% CI: 0.23–0.97; p=0.041). Triple-negative (TN) brain-metastatic cells were found to have increased β2-adrenergic receptor mRNA and protein expression relative to TN primary cells. In response to β2-adrenergic receptor activation, TN brain-metastatic cells also exhibited increased cell proliferation and migration relative to the control. These effects were abrogated by propranolol. Propranolol decreased β2-adrenergic receptor-activated invasion. In vivo, propranolol treatment of TN brain-metastatic cells decreased establishment of brain metastases. Our results suggest that stress and corresponding β2-activation may promote the establishment of brain metastases of TN breast cancer cells. In addition, our data suggest a benefit to perioperative β-blockade during surgery-induced stress with respect to breast cancer recurrence and metastases. PMID:27035124

The effect of brain size evolution on feeding propensity, digestive efficiency, and juvenile growth

PubMed Central

Kotrschal, Alexander; Corral‐Lopez, Alberto; Szidat, Sönke; Kolm, Niclas

2015-01-01

One key hypothesis in the study of brain size evolution is the expensive tissue hypothesis; the idea that increased investment into the brain should be compensated by decreased investment into other costly organs, for instance the gut. Although the hypothesis is supported by both comparative and experimental evidence, little is known about the potential changes in energetic requirements or digestive traits following such evolutionary shifts in brain and gut size. Organisms may meet the greater metabolic requirements of larger brains despite smaller guts via increased food intake or better digestion. But increased investment in the brain may also hamper somatic growth. To test these hypotheses we here used guppy (Poecilia reticulata) brain size selection lines with a pronounced negative association between brain and gut size and investigated feeding propensity, digestive efficiency (DE), and juvenile growth rate. We did not find any difference in feeding propensity or DE between large‐ and small‐brained individuals. Instead, we found that large‐brained females had slower growth during the first 10 weeks after birth. Our study provides experimental support that investment into larger brains at the expense of gut tissue carries costs that are not necessarily compensated by a more efficient digestive system. PMID:26420573

The role of gangliosides in brain development and the potential benefits of perinatal supplementation.

PubMed

Ryan, Jennifer M; Rice, Gregory E; Mitchell, Murray D

2013-11-01

The maternal diet provides critical nutrients that can influence fetal and infant brain development and function. This review highlights the potential benefits of maternal dietary ganglioside supplementation on fetal and infant brain development. English-language systematic reviews, preclinical studies, and clinical studies were obtained through searches on PubMed. Reports were selected if they included benefits and harms of maternal ganglioside supplementation during pregnancy or ganglioside-supplemented formula after pregnancy. The potential benefits of ganglioside supplementation were explored by investigating the following: (1) their role in neural development, (2) their therapeutic use in neural injury and disease, (3) their presence in human breast milk, and (4) their use as a dietary supplement during or after pregnancy. Preclinical studies indicate that ganglioside supplementation at high doses (1% of total dietary intake) can significantly increase cognitive development and body weight when given prenatally. However, lower ganglioside supplementation doses have no beneficial cognitive effects, even when given throughout pregnancy and lactation. In human clinical trials, infants given formula supplemented with gangliosides showed increased cognitive development and an increase in ganglioside content. Ganglioside supplementation may promote brain development and function in offspring when administered at the optimum dosage. We propose that prenatal maternal dietary supplementation with gangliosides throughout pregnancy may promote greater long-term effects on brain development and function. Before this concept can be encouraged in preconception clinics, future research and clinical trials are needed to confirm the ability of dietary gangliosides to improve cognitive development, but available results already encourage this area of research. © 2013.

Processing speed in recurrent visual networks correlates with general intelligence.

PubMed

Jolij, Jacob; Huisman, Danielle; Scholte, Steven; Hamel, Ronald; Kemner, Chantal; Lamme, Victor A F

2007-01-08

Studies on the neural basis of general fluid intelligence strongly suggest that a smarter brain processes information faster. Different brain areas, however, are interconnected by both feedforward and feedback projections. Whether both types of connections or only one of the two types are faster in smarter brains remains unclear. Here we show, by measuring visual evoked potentials during a texture discrimination task, that general fluid intelligence shows a strong correlation with processing speed in recurrent visual networks, while there is no correlation with speed of feedforward connections. The hypothesis that a smarter brain runs faster may need to be refined: a smarter brain's feedback connections run faster.

Semantic relatedness between words in each individual brain: an event-related potential study.

PubMed

Hata, Masahiro; Homae, Fumitaka; Hagiwara, Hiroko

2011-08-26

The relationship between 2 words is judged by the meanings of words. Here, we examined how the semantic relatedness of words is structured in each individual brain. During measurements of event-related potentials (ERPs), participants performed semantic-relatedness judgments of word pairs. For each participant, we divided word pairs into 2 groups--related and unrelated pairs--and compared their ERPs. All of the participants showed a significant N400 effect. However, when we applied an identical grouping of pairs, this effect was observed only in half the number of the participants. These results show that our single-subject analysis of N400 extracted semantic relatedness of words in the individual brain. Future studies using this analysis will clarify the organization of the mental lexicon. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Plasticity following early-life brain injury: Insights from quantitative MRI.

PubMed

Fiori, Simona; Guzzetta, Andrea

2015-03-01

Over the last decade, the application of novel advanced neuroimaging techniques to study congenital brain damage has provided invaluable insights into the mechanisms underlying early neuroplasticity. The concept that is clearly emerging, both from human and nun-human studies, is that functional reorganization in the immature brain is substantially different from that of the more mature, developed brain. This applies to the reorganization of language, the sensorimotor system, and the visual system. The rapid implementation and development of higher order imaging methods will offer increased, currently unavailable knowledge about the specific mechanisms of cerebral plasticity in infancy, which is essential to support the development of early therapeutic interventions aimed at supporting and enhancing functional reorganization during a time of greatest potential brain plasticity. Copyright © 2015. Published by Elsevier Inc.

Intranasal mucoadhesive microemulsions of clonazepam: preliminary studies on brain targeting.

PubMed

Vyas, Tushar K; Babbar, A K; Sharma, R K; Singh, Shashi; Misra, Ambikanandan

2006-03-01

The aim of this investigation was to prepare clonazepam microemulsions (CME) for rapid drug delivery to the brain to treat acute status epileptic patients and to characterize and evaluate the performance of CME in vitro and in vivo in rats. The CME were prepared by the titration method and were characterized for globule size and size distribution, zeta potential, and drug content. CME was radiolabeled with (99m)Tc (technetium) and biodistribution of drug in the brain was studied in Swiss albino rats after intranasal and intravenous administrations. Brain scintigraphy imaging in rabbits was also performed to ascertain the uptake of the drug into the brain. Pre and postCME formulation treated human nasal mucosa was subjected to transmission electron microscopy to investigate the mechanism of drug uptake across the nasal mucosa. CME were transparent and stable with mean globule size of 15 +/- 10 nm and zeta potential of -30 mV to -40 mV. (99m)Tc-labeled clonazepam solution ((99m)Tc CS)/ clonazepam microemulsion (CME)/clonazepam mucoadhesive microemulsion (CMME) were found to be stable and suitable for in vivo studies. Brain/blood uptake ratios at 0.50 hour (h) following intranasal CMME, CME, clonazepam solution (CS), and intravenous CME administrations were found to be 0.67, 0.50, 0.48, and 0.13, respectively indicating more effective targeting with intranasal administration and best targeting of the brain with intranasal CMME. Brain/blood ratio at all sampling points up to 8 h following intranasal administration of CMME compared to intravenous was found to be twofold higher indicating larger extent of distribution of the drug in brain. Rabbit brain scintigraphy also showed higher intranasal uptake of the drug into the brain. Transmission electron microscopy revealed significant accretion of CMME within interstitial spaces and paracellular mode of transport due to stretching of the tight junctions present in the nasal mucosa. This investigation demonstrates a more rapid and larger extent of transport of clonazepam into the rat brain with intranasal CMME, which may prove useful in treating acute status epileptics. Copyright 2006 Wiley-Liss, Inc. and the American Pharmacists Association.

Polyethyleneimine-modified iron oxide nanoparticles for brain tumor drug delivery using magnetic targeting and intra-carotid administration

PubMed Central

Chertok, Beata; David, Allan E.; Yang, Victor C.

2010-01-01

This study aimed to examine the applicability of polyethyleneimine (PEI)-modified magnetic nanoparticles (GPEI) as a potential vascular drug/gene carrier to brain tumors. In vitro, GPEI exhibited high cell association and low cell toxicity – properties which are highly desirable for intracellular drug/gene delivery. In addition, a high saturation magnetization of 93 emu/g Fe was expected to facilitate magnetic targeting of GPEI to brain tumor lesions. However, following intravenous administration, GPEI could not be magnetically accumulated in tumors of rats harboring orthotopic 9L-gliosarcomas due to its poor pharmacokinetic properties, reflected by a negligibly low plasma AUC of 12 ± 3 μg Fe/ml*min. To improve “passive” GPEI presentation to brain tumor vasculature for subsequent “active” magnetic capture, we examined the intra-carotid route as an alternative for nanoparticle administration. Intra-carotid administration in conjunction with magnetic targeting resulted in 30-fold (p = 0.002) increase in tumor entrapment of GPEI compared to that seen with intravenous administration. In addition, magnetic accumulation of cationic GPEI (ζ-potential = + 37.2 mV) in tumor lesions was 5.2-fold higher (p = 0.004) than that achieved with slightly anionic G100 (ζ-potential = −12 mV) following intra-carotid administration, while no significant accumulation difference was detected between the two types of nanoparticles in the contra-lateral brain (p = 0.187). These promising results warrant further investigation of GPEI as a potential cell-permeable, magnetically-responsive platform for brain tumor delivery of drugs and genes. PMID:20494439

Polyethyleneimine-modified iron oxide nanoparticles for brain tumor drug delivery using magnetic targeting and intra-carotid administration.

PubMed

Chertok, Beata; David, Allan E; Yang, Victor C

2010-08-01

This study aimed to examine the applicability of polyethyleneimine (PEI)-modified magnetic nanoparticles (GPEI) as a potential vascular drug/gene carrier to brain tumors. In vitro, GPEI exhibited high cell association and low cell toxicity--properties which are highly desirable for intracellular drug/gene delivery. In addition, a high saturation magnetization of 93 emu/g Fe was expected to facilitate magnetic targeting of GPEI to brain tumor lesions. However, following intravenous administration, GPEI could not be magnetically accumulated in tumors of rats harboring orthotopic 9L-gliosarcomas due to its poor pharmacokinetic properties, reflected by a negligibly low plasma AUC of 12 +/- 3 microg Fe/ml min. To improve "passive" GPEI presentation to brain tumor vasculature for subsequent "active" magnetic capture, we examined the intra-carotid route as an alternative for nanoparticle administration. Intra-carotid administration in conjunction with magnetic targeting resulted in 30-fold (p=0.002) increase in tumor entrapment of GPEI compared to that seen with intravenous administration. In addition, magnetic accumulation of cationic GPEI (zeta-potential = + 37.2 mV) in tumor lesions was 5.2-fold higher (p=0.004) than that achieved with slightly anionic G100 (zeta-potential= -12 mV) following intra-carotid administration, while no significant accumulation difference was detected between the two types of nanoparticles in the contra-lateral brain (p=0.187). These promising results warrant further investigation of GPEI as a potential cell-permeable, magnetically-responsive platform for brain tumor delivery of drugs and genes. 2010 Elsevier Ltd. All rights reserved.

Therapeutic potential of systemic brain rejuvenation strategies for neurodegenerative disease

PubMed Central

Horowitz, Alana M.; Villeda, Saul A.

2017-01-01

Neurodegenerative diseases are a devastating group of conditions that cause progressive loss of neuronal integrity, affecting cognitive and motor functioning in an ever-increasing number of older individuals. Attempts to slow neurodegenerative disease advancement have met with little success in the clinic; however, a new therapeutic approach may stem from classic interventions, such as caloric restriction, exercise, and parabiosis. For decades, researchers have reported that these systemic-level manipulations can promote major functional changes that extend organismal lifespan and healthspan. Only recently, however, have the functional effects of these interventions on the brain begun to be appreciated at a molecular and cellular level. The potential to counteract the effects of aging in the brain, in effect rejuvenating the aged brain, could offer broad therapeutic potential to combat dementia-related neurodegenerative disease in the elderly. In particular, results from heterochronic parabiosis and young plasma administration studies indicate that pro-aging and rejuvenating factors exist in the circulation that can independently promote or reverse age-related phenotypes. The recent demonstration that human umbilical cord blood similarly functions to rejuvenate the aged brain further advances this work to clinical translation. In this review, we focus on these blood-based rejuvenation strategies and their capacity to delay age-related molecular and functional decline in the aging brain. We discuss new findings that extend the beneficial effects of young blood to neurodegenerative disease models. Lastly, we explore the translational potential of blood-based interventions, highlighting current clinical trials aimed at addressing therapeutic applications for the treatment of dementia-related neurodegenerative disease in humans. PMID:28815019

P-glycoprotein Inhibition Increases the Brain Distribution and Antidepressant-Like Activity of Escitalopram in Rodents

PubMed Central

O'Brien, Fionn E; O'Connor, Richard M; Clarke, Gerard; Dinan, Timothy G; Griffin, Brendan T; Cryan, John F

2013-01-01

Despite the clinical prevalence of the antidepressant escitalopram, over 30% of escitalopram-treated patients fail to respond to treatment. Recent gene association studies have highlighted a potential link between the drug efflux transporter P-glycoprotein (P-gp) and response to escitalopram. The present studies investigated pharmacokinetic and pharmacodynamic interactions between P-gp and escitalopram. In vitro bidirectional transport studies revealed that escitalopram is a transported substrate of human P-gp. Microdialysis-based pharmacokinetic studies demonstrated that administration of the P-gp inhibitor cyclosporin A resulted in increased brain levels of escitalopram without altering plasma escitalopram levels in the rat, thereby showing that P-gp restricts escitalopram transport across the blood–brain barrier (BBB) in vivo. The tail suspension test (TST) was carried out to elucidate the pharmacodynamic impact of P-gp inhibition on escitalopram effect in a mouse model of antidepressant activity. Pre-treatment with the P-gp inhibitor verapamil enhanced the response to escitalopram in the TST. Taken together, these data indicate that P-gp may restrict the BBB transport of escitalopram in humans, potentially resulting in subtherapeutic brain concentrations in certain patients. Moreover, by verifying that increasing escitalopram delivery to the brain by P-gp inhibition results in enhanced antidepressant-like activity, we suggest that adjunctive treatment with a P-gp inhibitor may represent a beneficial approach to augment escitalopram therapy in depression. PMID:23670590

Emergency department injury surveillance and aetiological research: bridging the gap with the two-stage case-control study design.

PubMed

Hagel, Brent E

2011-04-01

To provide an overview of the two-stage case-control study design and its potential application to ED injury surveillance data and to apply this approach to published ED data on the relation between brain injury and bicycle helmet use. Relevant background is presented on injury aetiology and case-control methodology with extension to the two-stage case-control design in the context of ED injury surveillance. The design is then applied to data from a published case-control study of the relation between brain injury and bicycle helmet use with motor vehicle involvement considered as a potential confounder. Taking into account the additional sampling at the second stage, the adjusted and corrected odds ratio and 95% confidence interval for the brain injury-helmet use relation is presented and compared with the estimate from the entire original dataset. Contexts where the two-stage case-control study design might be most appropriately applied to ED injury surveillance data are suggested. The adjusted odds ratio for the relation between brain injury and bicycle helmet use based on all data (n = 2833) from the original study was 0.34 (95% CI 0.25 to 0.46) compared with an estimate from a two-stage case-control design of 0.35 (95% CI 0.25 to 0.48) using only a fraction of the original subjects (n = 480). Application of the two-stage case-control study design to ED injury surveillance data has the potential to dramatically reduce study time and resource costs with acceptable losses in statistical efficiency.

A new methodical approach in neuroscience: assessing inter-personal brain coupling using functional near-infrared imaging (fNIRI) hyperscanning.

PubMed

Scholkmann, Felix; Holper, Lisa; Wolf, Ursula; Wolf, Martin

2013-11-27

Since the first demonstration of how to simultaneously measure brain activity using functional magnetic resonance imaging (fMRI) on two subjects about 10 years ago, a new paradigm in neuroscience is emerging: measuring brain activity from two or more people simultaneously, termed "hyperscanning". The hyperscanning approach has the potential to reveal inter-personal brain mechanisms underlying interaction-mediated brain-to-brain coupling. These mechanisms are engaged during real social interactions, and cannot be captured using single-subject recordings. In particular, functional near-infrared imaging (fNIRI) hyperscanning is a promising new method, offering a cost-effective, easy to apply and reliable technology to measure inter-personal interactions in a natural context. In this short review we report on fNIRI hyperscanning studies published so far and summarize opportunities and challenges for future studies.

Clinical study and numerical simulation of brain cancer dynamics under radiotherapy

NASA Astrophysics Data System (ADS)

Nawrocki, S.; Zubik-Kowal, B.

2015-05-01

We perform a clinical and numerical study of the progression of brain cancer tumor growth dynamics coupled with the effects of radiotherapy. We obtained clinical data from a sample of brain cancer patients undergoing radiotherapy and compare it to our numerical simulations to a mathematical model of brain tumor cell population growth influenced by radiation treatment. We model how the body biologically receives a physically delivered dose of radiation to the affected tumorous area in the form of a generalized LQ model, modified to account for the conversion process of sublethal lesions into lethal lesions at high radiation doses. We obtain good agreement between our clinical data and our numerical simulations of brain cancer progression given by the mathematical model, which couples tumor growth dynamics and the effect of irradiation. The correlation, spanning a wide dataset, demonstrates the potential of the mathematical model to describe the dynamics of brain tumor growth influenced by radiotherapy.

Functional magnetic resonance imaging can be used to explore tactile and nociceptive processing in the infant brain

PubMed Central

Williams, Gemma; Fabrizi, Lorenzo; Meek, Judith; Jackson, Deborah; Tracey, Irene; Robertson, Nicola; Slater, Rebeccah; Fitzgerald, Maria

2015-01-01

Aim Despite the importance of neonatal skin stimulation, little is known about activation of the newborn human infant brain by sensory stimulation of the skin. We carried out functional magnetic resonance imaging (fMRI) to assess the feasibility of measuring brain activation to a range of mechanical stimuli applied to the skin of neonatal infants. Methods We studied 19 term infants with a mean age of 13 days. Brain activation was measured in response to brushing, von Frey hair (vFh) punctate stimulation and, in one case, nontissue damaging pinprick stimulation of the plantar surface of the foot. Initial whole brain analysis was followed by region of interest analysis of specific brain areas. Results Distinct patterns of functional brain activation were evoked by brush and vFh punctate stimulation, which were reduced, but still present, under chloral hydrate sedation. Brain activation increased with increasing stimulus intensity. The feasibility of using pinprick stimulation in fMRI studies was established in one unsedated healthy full-term infant. Conclusion Distinct brain activity patterns can be measured in response to different modalities and intensities of skin sensory stimulation in term infants. This indicates the potential for fMRI studies in exploring tactile and nociceptive processing in the infant brain. PMID:25358870

Basic emotion processing and the adolescent brain: Task demands, analytic approaches, and trajectories of changes.

PubMed

Del Piero, Larissa B; Saxbe, Darby E; Margolin, Gayla

2016-06-01

Early neuroimaging studies suggested that adolescents show initial development in brain regions linked with emotional reactivity, but slower development in brain structures linked with emotion regulation. However, the increased sophistication of adolescent brain research has made this picture more complex. This review examines functional neuroimaging studies that test for differences in basic emotion processing (reactivity and regulation) between adolescents and either children or adults. We delineated different emotional processing demands across the experimental paradigms in the reviewed studies to synthesize the diverse results. The methods for assessing change (i.e., analytical approach) and cohort characteristics (e.g., age range) were also explored as potential factors influencing study results. Few unifying dimensions were found to successfully distill the results of the reviewed studies. However, this review highlights the potential impact of subtle methodological and analytic differences between studies, need for standardized and theory-driven experimental paradigms, and necessity of analytic approaches that are can adequately test the trajectories of developmental change that have recently been proposed. Recommendations for future research highlight connectivity analyses and non-linear developmental trajectories, which appear to be promising approaches for measuring change across adolescence. Recommendations are made for evaluating gender and biological markers of development beyond chronological age. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Basic emotion processing and the adolescent brain: Task demands, analytic approaches, and trajectories of changes

PubMed Central

Del Piero, Larissa B.; Saxbe, Darby E.; Margolin, Gayla

2016-01-01

Early neuroimaging studies suggested that adolescents show initial development in brain regions linked with emotional reactivity, but slower development in brain structures linked with emotion regulation. However, the increased sophistication of adolescent brain research has made this picture more complex. This review examines functional neuroimaging studies that test for differences in basic emotion processing (reactivity and regulation) between adolescents and either children or adults. We delineated different emotional processing demands across the experimental paradigms in the reviewed studies to synthesize the diverse results. The methods for assessing change (i.e., analytical approach) and cohort characteristics (e.g., age range) were also explored as potential factors influencing study results. Few unifying dimensions were found to successfully distill the results of the reviewed studies. However, this review highlights the potential impact of subtle methodological and analytic differences between studies, need for standardized and theory-driven experimental paradigms, and necessity of analytic approaches that are can adequately test the trajectories of developmental change that have recently been proposed. Recommendations for future research highlight connectivity analyses and nonlinear developmental trajectories, which appear to be promising approaches for measuring change across adolescence. Recommendations are made for evaluating gender and biological markers of development beyond chronological age. PMID:27038840

In vivo studies of brain development by magnetic resonance techniques.

PubMed

Inder, T E; Huppi, P S

2000-01-01

Understanding of the morphological development of the human brain has largely come from neuropathological studies obtained postmortem. Magnetic resonance (MR) techniques have recently allowed the provision of detailed structural, metabolic, and functional information in vivo on the human brain. These techniques have been utilized in studies from premature infants to adults and have provided invaluable data on the sequence of normal human brain development. This article will focus on MR techniques including conventional structural MR imaging techniques, quantitative morphometric MR techniques, diffusion weighted MR techniques, and MR spectroscopy. In order to understand the potential applications and limitations of MR techniques, relevant physical and biological principles for each of the MR techniques are first reviewed. This is followed by a review of the understanding of the sequence of normal brain development utilizing these techniques. MRDD Research Reviews 6:59-67, 2000. Copyright 2000 Wiley-Liss, Inc.

Analysis and asynchronous detection of gradually unfolding errors during monitoring tasks

NASA Astrophysics Data System (ADS)

Omedes, Jason; Iturrate, Iñaki; Minguez, Javier; Montesano, Luis

2015-10-01

Human studies on cognitive control processes rely on tasks involving sudden-onset stimuli, which allow the analysis of these neural imprints to be time-locked and relative to the stimuli onset. Human perceptual decisions, however, comprise continuous processes where evidence accumulates until reaching a boundary. Surpassing the boundary leads to a decision where measured brain responses are associated to an internal, unknown onset. The lack of this onset for gradual stimuli hinders both the analyses of brain activity and the training of detectors. This paper studies electroencephalographic (EEG)-measurable signatures of human processing for sudden and gradual cognitive processes represented as a trajectory mismatch under a monitoring task. Time-locked potentials and brain-source analysis of the EEG of sudden mismatches revealed the typical components of event-related potentials and the involvement of brain structures related to cognitive control processing. For gradual mismatch events, time-locked analyses did not show any discernible EEG scalp pattern, despite related brain areas being, to a lesser extent, activated. However, and thanks to the use of non-linear pattern recognition algorithms, it is possible to train an asynchronous detector on sudden events and use it to detect gradual mismatches, as well as obtaining an estimate of their unknown onset. Post-hoc time-locked scalp and brain-source analyses revealed that the EEG patterns of detected gradual mismatches originated in brain areas related to cognitive control processing. This indicates that gradual events induce latency in the evaluation process but that similar brain mechanisms are present in sudden and gradual mismatch events. Furthermore, the proposed asynchronous detection model widens the scope of applications of brain-machine interfaces to other gradual processes.

Memantine transport across the mouse blood-brain barrier is mediated by a cationic influx H+ antiporter.

PubMed

Mehta, Dharmini C; Short, Jennifer L; Nicolazzo, Joseph A

2013-12-02

Memantine (MEM) is prescribed in mono and combination therapies for treating the symptoms of moderate to severe Alzheimer's disease (AD). Despite MEM being widely prescribed with other AD and non-AD medicines, very little is known about its mechanism of transport across the blood-brain barrier (BBB), and whether the nature of this transport lends MEM to a potential for drug-drug interactions at the BBB. Therefore, the purpose of this study was to characterize the mechanisms facilitating MEM brain uptake in Swiss Outbred mice using an in situ transcardiac perfusion technique, and identify the putative transporter involved in MEM disposition into the brain. Following transcardiac perfusion of MEM with increasing concentrations, the brain uptake of MEM was observed to be saturable. Furthermore, MEM brain uptake was reduced (up to 55%) by various cationic transporter inhibitors (amantadine, quinine, tetraethylammonium, choline and carnitine) and was dependent on extracellular pH, while being independent of membrane depolarization and the presence of Na(+) in the perfusate. In addition, MEM brain uptake was observed to be sensitive to changes in intracellular pH, hence, likely to be driven by H(+)/MEM antiport mechanisms. Taken together, these findings implicate the involvement of an organic cation transporter regulated by proton antiport mechanisms in the transport of MEM across the mouse BBB, possibly the organic cation/carnitine transporter, OCTN1. These studies also clearly demonstrate the brain uptake of MEM is significantly reduced by other cationic compounds, highlighting the need to consider the possibility of drug interactions with MEM at the BBB, potentially leading to reduced brain uptake and, therefore, altered efficacy of MEM when used in patients on multidrug regimens.

Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human Infant Brain

PubMed Central

Lieblein-Boff, Jacqueline C.; Johnson, Elizabeth J.; Kennedy, Adam D.; Lai, Chron-Si; Kuchan, Matthew J.

2015-01-01

Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula, and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with macular and postmortem brain lutein concentrations. Furthermore, lutein was found to preferentially accumulate in the infant brain in comparison to other carotenoids that are predominant in diet. While lutein is consistently related to cognitive function, the mechanisms by which lutein may influence cognition are not clear. In an effort to identify potential mechanisms through which lutein might influence neurodevelopment, an exploratory study relating metabolite signatures and lutein was completed. Post-mortem metabolomic analyses were performed on human infant brain tissues in three regions important for learning and memory: the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were compared to lutein concentration, and correlations were identified and reported here. A total of 1276 correlations were carried out across all brain regions. Of 427 metabolites analyzed, 257 were metabolites of known identity. Unidentified metabolite correlations (510) were excluded. In addition, moderate correlations with xenobiotic relationships (2) or those driven by single outliers (3) were excluded from further study. Lutein concentrations correlated with lipid pathway metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine. These correlations were often brain region—specific. Revealing relationships between lutein and metabolic pathways may help identify potential candidates on which to complete further analyses and may shed light on important roles of lutein in the human brain during development. PMID:26317757

The neurovascular complexity index as a potential indicator of traumatic brain injury severity: A case-series study.

PubMed

Howard, Jeffrey T; Janak, Jud C; Bukhman, Vladislav; Robertson, Claudia; Frolov, Iurii; Nawn, Corinne D; Schiller, Alicia M; Convertino, Victor A

2017-07-01

Multimodal monitoring of brain physiology following a traumatic brain injury (TBI) shows promise as a strategy to improve management and outcomes of TBI patients within civilian and military trauma. Valid and reliable measures of different aspects of brain physiology following a TBI could prove critical to accurately capturing these changes. Using a case-series design with a control subject group comparison, we evaluated a new proprietary algorithm called the Neurovascular Complexity Index (NCI) using transcranial Doppler to noninvasively obtain measures of cerebral blood flow variability. Baseline NCI data from 169 control subjects were compared with 12 patients with moderate to severe TBI. Patients with TBI exhibited significantly greater mean and variability in NCI scores compared with control subjects (F = 195.48; p < 0.001). The mean absolute deviation (MAD) of NCI scores increased significantly and in a monotonic fashion with severity of injury, where control subjects exhibited a small MAD of 0.44, patients with moderate TBI had a higher MAD of 4.20, and patients with severe TBI had an MAD of 6.51 (p < 0.001). Advancement in multimodal monitoring of TBI patients is important in reducing the potential risk of secondary injury. This study reports results indicating that a new noninvasive quantifiable assessment of TBI based on a noninvasive measure of cerebral blood flow variability shows potential for continuous monitoring and early identification of brain-injured patients, deployable in far-forward military environments, to better inform individualized management. Case series, level IV.

Clarifying relations between dispositional aggression and brain potential response: overlapping and distinct contributions of impulsivity and stress reactivity.

PubMed

Venables, Noah C; Patrick, Christopher J; Hall, Jason R; Bernat, Edward M

2011-03-01

Impulsive-aggressive individuals exhibit deficits in amplitude of the P3 brain potential response, however, it remains unclear how separable dispositional traits account for this association. The current study sought to clarify the basis of this association by examining contributions of trait impulsiveness and stress reactivity to the observed relationship between dispositional aggression and amplitude of the P3 brain potential response in a visual novelty-oddball procedure. A significant negative association was found between aggressiveness and amplitude of P3 response to both target and novel stimuli over frontal-central scalp sites. Impulsivity showed a parallel inverse relationship with P3 amplitude, attributable to its overlap with dispositional aggression. In contrast, stress reactivity did not exhibit a zero-order association with P3 amplitude, but modestly predicted P3 in a positive direction after accounting for its overlap with aggression. Results are discussed in terms of their implications for individual difference variables and brain processes underlying impulsive-aggressive behavior. Copyright © 2011 Elsevier B.V. All rights reserved.

Hypoxic stress up-regulates Kir2.1 expression and facilitates cell proliferation in brain capillary endothelial cells.

PubMed

Yamamura, Hideto; Suzuki, Yoshiaki; Yamamura, Hisao; Asai, Kiyofumi; Imaizumi, Yuji

2016-08-05

The blood-brain barrier (BBB) is mainly composed of brain capillary endothelial cells (BCECs), astrocytes and pericytes. Brain ischemia causes hypoxic encephalopathy and damages BBB. However, it remains still unclear how hypoxia affects BCECs. In the present study, t-BBEC117 cells, an immortalized bovine brain endothelial cell line, were cultured under hypoxic conditions at 4-5% oxygen for 72 h. This hypoxic stress caused hyperpolarization of resting membrane potential. Patch-clamp recordings revealed a marked increase in Ba(2+)-sensitive inward rectifier K(+) current in t-BBEC117 cells after hypoxic culture. Western blot and real-time PCR analyses showed that Kir2.1 expression was significantly up-regulated at protein level but not at mRNA level after the hypoxic culture. Ca(2+) imaging study revealed that the hypoxic stress enhanced store-operated Ca(2+) (SOC) entry, which was significantly reduced in the presence of 100 μM Ba(2+). On the other hand, the expression of SOC channels such as Orai1, Orai2, and transient receptor potential channels was not affected by hypoxic stress. MTT assay showed that the hypoxic stress significantly enhanced t-BBEC117 cell proliferation, which was inhibited by approximately 60% in the presence of 100 μM Ba(2+). We first show here that moderate cellular stress by cultivation under hypoxic conditions hyperpolarizes membrane potential via the up-regulation of functional Kir2.1 expression and presumably enhances Ca(2+) entry, resulting in the facilitation of BCEC proliferation. These findings suggest potential roles of Kir2.1 expression in functional changes of BCECs in BBB following ischemia. Copyright © 2016 Elsevier Inc. All rights reserved.

The bumetanide prodrug BUM5, but not bumetanide, potentiates the antiseizure effect of phenobarbital in adult epileptic mice.

PubMed

Erker, Thomas; Brandt, Claudia; Töllner, Kathrin; Schreppel, Philipp; Twele, Friederike; Schidlitzki, Alina; Löscher, Wolfgang

2016-05-01

The loop diuretic bumetanide has been reported to potentiate the antiseizure activity of phenobarbital in rodent models of neonatal seizures, most likely as a result of inhibition of the chloride importer Na-K-Cl cotransporter isoform 1 (NKCC1) in the brain. In view of the intractability of neonatal seizures, the preclinical findings prompted a clinical trial in neonates on bumetanide as an add-on to phenobarbital, which, however, had to be terminated because of ototoxicity and lack of efficacy. We have recently shown that bumetanide penetrates only poorly into the brain, so that we developed lipophilic prodrugs such as BUM5, the N,N-dimethylaminoethylester of bumetanide, which penetrate more easily into the brain and are converted to bumetanide. In the present study, we used a new strategy to test whether BUM5 is more potent than bumetanide in potentiating the antiseizure effect of phenobarbital. Adult mice were made epileptic by pilocarpine, and the antiseizure effects of bumetanide, BUM5, and phenobarbital alone or in combination were determined by the maximal electroshock seizure threshold test. In nonepileptic mice, only phenobarbital exerted seizure threshold-increasing activity, and this was not potentiated by the NKCC1 inhibitors. In contrast, a marked potentiation of phenobarbital by BUM5, but not bumetanide, was determined in epileptic mice. Thus, bumetanide is not capable of potentiating phenobarbital's antiseizure effect in an adult mouse model, which, however, can be overcome by using the prodrug BUM5. These data substantiate that BUM5 is a promising tool compound for target validation and proof-of-concept studies on the role of NKCC1 in brain diseases. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Error-related processing following severe traumatic brain injury: An event-related functional magnetic resonance imaging (fMRI) study

PubMed Central

Sozda, Christopher N.; Larson, Michael J.; Kaufman, David A.S.; Schmalfuss, Ilona M.; Perlstein, William M.

2011-01-01

Continuous monitoring of one’s performance is invaluable for guiding behavior towards successful goal attainment by identifying deficits and strategically adjusting responses when performance is inadequate. In the present study, we exploited the advantages of event-related functional magnetic resonance imaging (fMRI) to examine brain activity associated with error-related processing after severe traumatic brain injury (sTBI). fMRI and behavioral data were acquired while 10 sTBI participants and 12 neurologically-healthy controls performed a task-switching cued-Stroop task. fMRI data were analyzed using a random-effects whole-brain voxel-wise general linear model and planned linear contrasts. Behaviorally, sTBI patients showed greater error-rate interference than neurologically-normal controls. fMRI data revealed that, compared to controls, sTBI patients showed greater magnitude error-related activation in the anterior cingulate cortex (ACC) and an increase in the overall spatial extent of error-related activation across cortical and subcortical regions. Implications for future research and potential limitations in conducting fMRI research in neurologically-impaired populations are discussed, as well as some potential benefits of employing multimodal imaging (e.g., fMRI and event-related potentials) of cognitive control processes in TBI. PMID:21756946

Error-related processing following severe traumatic brain injury: an event-related functional magnetic resonance imaging (fMRI) study.

PubMed

Sozda, Christopher N; Larson, Michael J; Kaufman, David A S; Schmalfuss, Ilona M; Perlstein, William M

2011-10-01

Continuous monitoring of one's performance is invaluable for guiding behavior towards successful goal attainment by identifying deficits and strategically adjusting responses when performance is inadequate. In the present study, we exploited the advantages of event-related functional magnetic resonance imaging (fMRI) to examine brain activity associated with error-related processing after severe traumatic brain injury (sTBI). fMRI and behavioral data were acquired while 10 sTBI participants and 12 neurologically-healthy controls performed a task-switching cued-Stroop task. fMRI data were analyzed using a random-effects whole-brain voxel-wise general linear model and planned linear contrasts. Behaviorally, sTBI patients showed greater error-rate interference than neurologically-normal controls. fMRI data revealed that, compared to controls, sTBI patients showed greater magnitude error-related activation in the anterior cingulate cortex (ACC) and an increase in the overall spatial extent of error-related activation across cortical and subcortical regions. Implications for future research and potential limitations in conducting fMRI research in neurologically-impaired populations are discussed, as well as some potential benefits of employing multimodal imaging (e.g., fMRI and event-related potentials) of cognitive control processes in TBI. Copyright © 2011 Elsevier B.V. All rights reserved.

Potential therapeutic and protective effect of curcumin against stroke in the male albino stroke-induced model rats.

PubMed

Zhang, Yuanyuan; Yan, Yi; Cao, Yi; Yang, Yongtao; Zhao, Qing; Jing, Rui; Hu, Jiayi; Bao, Juan

2017-08-15

The present study was carried out to understand the therapeutic effect of curcumin (CUR) against stroke in the experimental animal model. The study investigates the healing effect of CUR on mitochondrial dysfunction and inflammation. Male albino, Wistar strain rats were used for the induction of middle cerebral artery occlusion (MCAO), and reperfusion. Enzyme-linked immunosorbent assay (ELISA) was used for the determination of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the brain region. Western blot analysis was used to determine the protein expression levels of Bax, Bcl-2, p53, and Sirt1. The water level was determined in brain region by using standard method. Experimental results indicated that the use of CUR significantly reduced brain edema and water content. IL-6 and TNF-α were significantly reduced in the brain region following use of CUR. Mitochondrial membrane potential (MMP) also reduced significantly after CUR treatment. Protein expression of p53 and Bax were significantly reduced, whereas Bcl-2 and Sirt1 were increased following CUR treatment. Taking all these data together, it is suggested that the use of CUR may be a potential therapeutic agent for the treatment of stroke. Copyright © 2017 Elsevier Inc. All rights reserved.

A neuro-inspired model-based closed-loop neuroprosthesis for the substitution of a cerebellar learning function in anesthetized rats

NASA Astrophysics Data System (ADS)

Hogri, Roni; Bamford, Simeon A.; Taub, Aryeh H.; Magal, Ari; Giudice, Paolo Del; Mintz, Matti

2015-02-01

Neuroprostheses could potentially recover functions lost due to neural damage. Typical neuroprostheses connect an intact brain with the external environment, thus replacing damaged sensory or motor pathways. Recently, closed-loop neuroprostheses, bidirectionally interfaced with the brain, have begun to emerge, offering an opportunity to substitute malfunctioning brain structures. In this proof-of-concept study, we demonstrate a neuro-inspired model-based approach to neuroprostheses. A VLSI chip was designed to implement essential cerebellar synaptic plasticity rules, and was interfaced with cerebellar input and output nuclei in real time, thus reproducing cerebellum-dependent learning in anesthetized rats. Such a model-based approach does not require prior system identification, allowing for de novo experience-based learning in the brain-chip hybrid, with potential clinical advantages and limitations when compared to existing parametric ``black box'' models.

Addition of visual noise boosts evoked potential-based brain-computer interface.

PubMed

Xie, Jun; Xu, Guanghua; Wang, Jing; Zhang, Sicong; Zhang, Feng; Li, Yeping; Han, Chengcheng; Li, Lili

2014-05-14

Although noise has a proven beneficial role in brain functions, there have not been any attempts on the dedication of stochastic resonance effect in neural engineering applications, especially in researches of brain-computer interfaces (BCIs). In our study, a steady-state motion visual evoked potential (SSMVEP)-based BCI with periodic visual stimulation plus moderate spatiotemporal noise can achieve better offline and online performance due to enhancement of periodic components in brain responses, which was accompanied by suppression of high harmonics. Offline results behaved with a bell-shaped resonance-like functionality and 7-36% online performance improvements can be achieved when identical visual noise was adopted for different stimulation frequencies. Using neural encoding modeling, these phenomena can be explained as noise-induced input-output synchronization in human sensory systems which commonly possess a low-pass property. Our work demonstrated that noise could boost BCIs in addressing human needs.

Tracing Activity Across the Whole Brain Neural Network with Optogenetic Functional Magnetic Resonance Imaging

PubMed Central

Lee, Jin Hyung

2011-01-01

Despite the overwhelming need, there has been a relatively large gap in our ability to trace network level activity across the brain. The complex dense wiring of the brain makes it extremely challenging to understand cell-type specific activity and their communication beyond a few synapses. Recent development of the optogenetic functional magnetic resonance imaging (ofMRI) provides a new impetus for the study of brain circuits by enabling causal tracing of activities arising from defined cell types and firing patterns across the whole brain. Brain circuit elements can be selectively triggered based on their genetic identity, cell body location, and/or their axonal projection target with temporal precision while the resulting network response is monitored non-invasively with unprecedented spatial and temporal accuracy. With further studies including technological innovations to bring ofMRI to its full potential, ofMRI is expected to play an important role in our system-level understanding of the brain circuit mechanism. PMID:22046160

State-of-the-art considerations in small cell lung cancer brain metastases

PubMed Central

Lukas, Rimas V.; Gondi, Vinai; Kamson, David O.; Kumthekar, Priya; Salgia, Ravi

2017-01-01

Background Small cell lung cancer (SCLC) frequently leads to development of brain metastases. These unfortunately continue to be associated with short survival. Substantial advances have been made in our understanding of the underlying biology of disease. This understanding on the background of previously evaluated and currently utilized therapeutic treatments can help guide the next steps in investigations into this disease with the potential to influence future treatments. Design A comprehensive review of the literature covering epidemiology, pathophysiology, imaging characteristics, prognosis, and therapeutic management of SCLC brain metastases was performed. Results SCLC brain metastases continue to have a poor prognosis. Both unique aspects of SCLC brain metastases as well as features seen more universally across other solid tumor brain metastases are discussed. Systemic therapeutic studies and radiotherapeutic approaches are reviewed. Conclusions A clearer understanding of SCLC brain metastases will help lay the framework for studies which will hopefully translate into meaningful therapeutic options for these patients. PMID:29050358

General anesthetics and cytotoxicity: possible implications for brain health.

PubMed

Armstrong, Ryden; Xu, Fenglian; Arora, Anish; Rasic, Nivez; Syed, Naweed I

2017-04-01

The search for agents that bring about faster induction and quicker recovery in the operating room have yielded numerous anesthetics whose mechanisms of action and potential toxic side effects remain unknown, especially in the young and aging brain. Taking advantage of our clinical and basic science expertise, here we subject the reader to an interesting perspective vis-à-vis the current applications of general anesthetics, and present evidence for their neurotoxic effects on the developing and elderly brains. Recent studies have called into question the safety of general anesthetics, especially with regards to potentially significant detrimental impacts on the developing brains of young children, and cognitive decline in the elderly - often following multiple episodes of anesthesia. Despite accumulating evidence from animal studies demonstrating that general anesthesia leads to neurodegeneration and cognitive impairment, to date a clear consensus on the impact of anesthetics in humans remains elusive. Because a direct impact of anesthetics on human neuronal networks is often difficult to deduce experimentally, most laboratories have resorted to animal models - albeit with limited success in translating these findings back to the clinic. Moreover, the precise mechanisms that lead to potential cognitive, learning, and memory decline in young and elderly patients also remain to be fully defined. This review will focus primarily on the cytotoxic effects of anesthetics, and offer some practical resolutions that may attenuate their long-term harm. An urgent need for studies on animal models and an increased focus on highly controlled prospective epidemiological studies is also reinforced.

Design and validation of a microfluidic device for blood-brain barrier monitoring and transport studies

NASA Astrophysics Data System (ADS)

Ugolini, Giovanni Stefano; Occhetta, Paola; Saccani, Alessandra; Re, Francesca; Krol, Silke; Rasponi, Marco; Redaelli, Alberto

2018-04-01

In vitro blood-brain barrier models are highly relevant for drug screening and drug development studies, due to the challenging task of understanding the transport mechanism of drug molecules through the blood-brain barrier towards the brain tissue. In this respect, microfluidics holds potential for providing microsystems that require low amounts of cells and reagent and can be potentially multiplexed for increasing the ease and throughput of the drug screening process. We here describe the design, development and validation of a microfluidic device for endothelial blood-brain barrier cell transport studies. The device comprises of two microstructured layers (top culture chamber and bottom collection chamber) sandwiching a porous membrane for the cell culture. Microstructured layers include two pairs of physical electrodes, embedded into the device layers by geometrically defined guiding channels with computationally optimized positions. These electrodes allow the use of commercial electrical measurement systems for monitoring trans-endothelial electrical resistance (TEER). We employed the designed device for performing preliminary assessment of endothelial barrier formation with murine brain endothelial cells (Br-bEnd5). Results demonstrate that cellular junctional complexes effectively form in the cultures (expression of VE-Cadherin and ZO-1) and that the TEER monitoring systems effectively detects an increase of resistance of the cultured cell layers indicative of tight junction formation. Finally, we validate the use of the described microsystem for drug transport studies demonstrating that Br-bEnd5 cells significantly hinder the transport of molecules (40 kDa and 4 kDa dextran) from the top culture chamber to the bottom collection chamber.

Analysis of wave III of brain stem auditory evoked potential waveforms during microvascular decompression of cranial nerve VII for hemifacial spasm.

PubMed

Thirumala, Parthasarathy D; Krishnaiah, Balaji; Crammond, Donald J; Habeych, Miguel E; Balzer, Jeffrey R

2014-04-01

Intraoperative monitoring of brain stem auditory evoked potential during microvascular decompression (MVD) prevent hearing loss (HL). Previous studies have shown that changes in wave III (wIII) are an early and sensitive sign of auditory nerve injury. To evaluate the changes of amplitude and latency of wIII of brain stem auditory evoked potential during MVD and its association with postoperative HL. Hearing loss was classified by American Academy of Otolaryngology - Head and Neck Surgery (AAO-HNS) criteria, based on changes in pure tone audiometry and speech discrimination score. Retrospective analysis of wIII in patients who underwent intraoperative monitoring with brain stem auditory evoked potential during MVD was performed. A univariate logistic regression analysis was performed on independent variables amplitude of wIII and latency of wIII at change max and On-Skin, or a final recording at the time of skin closure. A further analysis for the same variables was performed adjusting for the loss of wave. The latency of wIII was not found to be significantly different between groups I and II. The amplitude of wIII was significantly decreased in the group with HL. Regression analysis did not find any increased odds of HL with changes in the amplitude of wIII. Changes in wave III did not increase the odds of HL in patients who underwent brain stem auditory evoked potential s during MVD. This information might be valuable to evaluate the value of wIII as an alarm criterion during MVD to prevent HL.

Is the ferret a suitable species for studying perinatal brain injury?

PubMed Central

Empie, Kristen; Rangarajan, Vijayeta; Juul, Sandra E.

2016-01-01

Complications of prematurity often disrupt normal brain development and/or cause direct damage to the developing brain, resulting in poor neurodevelopmental outcomes. Physiologically relevant animal models of perinatal brain injury can advance our understanding of these influences and thereby provide opportunities to develop therapies and improve long-term outcomes. While there are advantages to currently available small animal models, there are also significant drawbacks that have limited translation of research findings to humans. Large animal models such as newborn pig, sheep and nonhuman primates have complex brain development more similar to humans, but these animals are expensive, and developmental testing of sheep and piglets is limited. Ferrets (Mustela putorius furo) are born lissencephalic and undergo postnatal cortical folding to form complex gyrencephalic brains. This review examines whether ferrets might provide a novel intermediate animal model of neonatal brain disease that has the benefit of a gyrified, altricial brain in a small animal. It summarizes attributes of ferret brain growth and development that make it an appealing animal in which to model perinatal brain injury. We postulate that because of their innate characteristics, ferrets have great potential in neonatal neurodevelopmental studies. PMID:26102988

Neuroprotection and neurotoxicity in the developing brain: an update on the effects of dexmedetomidine and xenon.

PubMed

Alam, Azeem; Suen, Ka Chun; Hana, Zac; Sanders, Robert D; Maze, Mervyn; Ma, Daqing

Growing and consistent preclinical evidence, combined with early clinical epidemiological observations, suggest potentially neurotoxic effects of commonly used anesthetic agents in the developing brain. This has prompted the FDA to issue a safety warning for all sedatives and anesthetics approved for use in children under three years of age. Recent studies have identified dexmedetomidine, the potent α2-adrenoceptor agonist, and xenon, the noble gas, as effective anesthetic adjuvants that are both less neurotoxic to the developing brain, and also possess neuroprotective properties in neonatal and other settings of acute ongoing neurologic injury. Dexmedetomidine and xenon are effective anesthetic adjuvants that appear to be less neurotoxic than other existing agents and have the potential to be neuroprotective in the neonatal and pediatric settings. Although results from recent clinical trials and case reports have indicated the neuroprotective potential of xenon and dexmedetomidine, additional randomized clinical trials corroborating these studies are necessary. By reviewing both the existing preclinical and clinical evidence on the neuroprotective effects of dexmedetomidine and xenon, we hope to provide insight into the potential clinical efficacy of these agents in the management of pediatric surgical patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Penetration and distribution of gadolinium-based contrast agents into the cerebrospinal fluid in healthy rats: a potential pathway of entry into the brain tissue.

PubMed

Jost, Gregor; Frenzel, Thomas; Lohrke, Jessica; Lenhard, Diana Constanze; Naganawa, Shinji; Pietsch, Hubertus

2017-07-01

Signal hyperintensity on unenhanced MRI in certain brain regions has been reported after multiple administrations of some, but not all, gadolinium-based contrast agents (GBCAs). One potential initial pathway of GBCA entry into the brain, infiltration from blood into the cerebrospinal fluid (CSF), was systematically evaluated in this preclinical study. GBCA infiltration and distribution in the CSF were investigated in healthy rats using repeated fluid-attenuated MRI up to 4 h after high-dose (1.8 mmol/kg) administration of six marketed and one experimental GBCA. Additionally, gadolinium measurements in CSF, blood and brain tissue samples (after 24 h) were performed using inductively coupled plasma mass spectrometry. Enhanced MRI signals in the CSF spaces with similar distribution kinetics were observed for all GBCAs. No substantial differences in the gadolinium concentrations among the marketed GBCAs were found in the CSF, blood or brain tissue. After 4.5 h, the concentration in the CSF was clearly higher than in blood but was almost completely cleared and lower than the brain tissue concentration after 24 h. In contrast to the brain signal hyperintensities, no differences in penetration and distribution into the CSF of healthy rats exist among the marketed GBCAs. • Gadolinium-based contrast agents can cross the blood-CSF barrier. • Fluid-attenuated MRI shows GBCA distribution with CSF flow. • GBCA structure and physicochemical properties do not impact CSF penetration and distribution. • GBCA clearance from CSF was almost complete within 24 h in rats. • CSF is a potential pathway of GBCA entry into the brain.

The effect of brain size evolution on feeding propensity, digestive efficiency, and juvenile growth.

PubMed

Kotrschal, Alexander; Corral-Lopez, Alberto; Szidat, Sönke; Kolm, Niclas

2015-11-01

One key hypothesis in the study of brain size evolution is the expensive tissue hypothesis; the idea that increased investment into the brain should be compensated by decreased investment into other costly organs, for instance the gut. Although the hypothesis is supported by both comparative and experimental evidence, little is known about the potential changes in energetic requirements or digestive traits following such evolutionary shifts in brain and gut size. Organisms may meet the greater metabolic requirements of larger brains despite smaller guts via increased food intake or better digestion. But increased investment in the brain may also hamper somatic growth. To test these hypotheses we here used guppy (Poecilia reticulata) brain size selection lines with a pronounced negative association between brain and gut size and investigated feeding propensity, digestive efficiency (DE), and juvenile growth rate. We did not find any difference in feeding propensity or DE between large- and small-brained individuals. Instead, we found that large-brained females had slower growth during the first 10 weeks after birth. Our study provides experimental support that investment into larger brains at the expense of gut tissue carries costs that are not necessarily compensated by a more efficient digestive system. © 2015 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

Long-term detection of Parkinsonian tremor activity from subthalamic nucleus local field potentials.

PubMed

Houston, Brady; Blumenfeld, Zack; Quinn, Emma; Bronte-Stewart, Helen; Chizeck, Howard

2015-01-01

Current deep brain stimulation paradigms deliver continuous stimulation to deep brain structures to ameliorate the symptoms of Parkinson's disease. This continuous stimulation has undesirable side effects and decreases the lifespan of the unit's battery, necessitating earlier replacement. A closed-loop deep brain stimulator that uses brain signals to determine when to deliver stimulation based on the occurrence of symptoms could potentially address these drawbacks of current technology. Attempts to detect Parkinsonian tremor using brain signals recorded during the implantation procedure have been successful. However, the ability of these methods to accurately detect tremor over extended periods of time is unknown. Here we use local field potentials recorded during a deep brain stimulation clinical follow-up visit 1 month after initial programming to build a tremor detection algorithm and use this algorithm to detect tremor in subsequent visits up to 8 months later. Using this method, we detected the occurrence of tremor with accuracies between 68-93%. These results demonstrate the potential of tremor detection methods for efficacious closed-loop deep brain stimulation over extended periods of time.

Increased Small-World Network Topology Following Deployment-Acquired Traumatic Brain Injury Associated with the Development of Post-Traumatic Stress Disorder.

PubMed

Rowland, Jared A; Stapleton-Kotloski, Jennifer R; Dobbins, Dorothy L; Rogers, Emily; Godwin, Dwayne W; Taber, Katherine H

2018-05-01

Cross-sectional and longitudinal studies in active duty and veteran cohorts have both demonstrated that deployment-acquired traumatic brain injury (TBI) is an independent risk factor for developing post-traumatic stress disorder (PTSD), beyond confounds such as combat exposure, physical injury, predeployment TBI, and pre-deployment psychiatric symptoms. This study investigated how resting-state brain networks differ between individuals who developed PTSD and those who did not following deployment-acquired TBI. Participants included postdeployment veterans with deployment-acquired TBI history both with and without current PTSD diagnosis. Graph metrics, including small-worldness, clustering coefficient, and modularity, were calculated from individually constructed whole-brain networks based on 5-min eyes-open resting-state magnetoencephalography (MEG) recordings. Analyses were adjusted for age and premorbid IQ. Results demonstrated that participants with current PTSD displayed higher levels of small-worldness, F(1,12) = 5.364, p < 0.039, partial eta squared = 0.309, and Cohen's d = 0.972, and clustering coefficient, F(1, 12) = 12.204, p < 0.004, partial eta squared = 0.504, and Cohen's d = 0.905, than participants without current PTSD. There were no between-group differences in modularity or the number of modules present. These findings are consistent with a hyperconnectivity hypothesis of the effect of TBI history on functional networks rather than a disconnection hypothesis, demonstrating increased levels of clustering coefficient rather than a decrease as might be expected; however, these results do not account for potential changes in brain structure. These results demonstrate the potential pathological sequelae of changes in functional brain networks following deployment-acquired TBI and represent potential neurobiological changes associated with deployment-acquired TBI that may increase the risk of subsequently developing PTSD.

Society for Neuro-Oncology 2014 annual meeting updates on central nervous system metastases.

PubMed

Lukas, Rimas V; Mehta, Minesh P; Lesniak, Maciej S

2015-06-01

The 19th Annual Meeting of the Society for Neuro-Oncology (SNO) took place in November of 2014. The focus of many abstracts, as well as the Education Day, was on recent advances in the study of central nervous system (CNS) metastases. Key studies evaluating the factors in tumors and their microenvironment associated with the development and growth of brain metastases are reviewed. Studies investigating the factors that independently influence survival in participants with brain metastases are presented. The Response Assessment for Neuro-Oncology criteria for brain metastases (RANO-BM) and the Neurological Assessment in Neuro-Oncology (NANO) criteria, which were both presented, are recapped. Studies are reviewed evaluating factors that influence survival outcomes in participants with brain metastases who were treated with radiotherapy. Studies investigating the potential risk of radiation necrosis with the combination of radiotherapy and immunotherapies are presented. Brain metastases-focused subset analyses from the ASCEND-1 trial for ALK-translocated non-small cell lung cancer are presented. Preclinical and clinical work on solid tumor leptomeningeal carcinomatosis is also covered. An overview is provided of treatment- related toxicities as well as important concepts that may influence strategies to protect against these toxicities. Key concepts regarding tumor biology, prognostication, response assessment, therapeutic management, and sequelae of treatment for CNS metastases are summarized. Advances in our understanding of the basic and clinical science of CNS metastases have the potential to improve outcomes for patients.

Social Media as a Communication Support for Persons with Mild Acquired Cognitive Impairment: A Social Network Analysis Study.

PubMed

Eghdam, Aboozar; Hamidi, Ulrika; Bartfai, Aniko; Koch, Sabine

2017-01-01

This study was conducted as a social network analysis of a Facebook group for Swedish speaking persons (1310 members) with perceived brain fatigue after an illness or injury to the brain to address the lack of research examining social media and the potential value of on-line support for persons with mild acquired cognitive impairment.

Local vs. volume conductance activity of field potentials in the human subthalamic nucleus

PubMed Central

Marmor, Odeya; Valsky, Dan; Joshua, Mati; Bick, Atira S; Arkadir, David; Tamir, Idit; Bergman, Hagai; Israel, Zvi

2017-01-01

Subthalamic nucleus field potentials have attracted growing research and clinical interest over the last few decades. However, it is unclear whether subthalamic field potentials represent locally generated neuronal subthreshold activity or volume conductance of the organized neuronal activity generated in the cortex. This study aimed at understanding of the physiological origin of subthalamic field potentials and determining the most accurate method for recording them. We compared different methods of recordings in the human subthalamic nucleus: spikes (300–9,000 Hz) and field potentials (3–100 Hz) recorded by monopolar micro- and macroelectrodes, as well as by differential-bipolar macroelectrodes. The recordings were done outside and inside the subthalamic nucleus during electrophysiological navigation for deep brain stimulation procedures (150 electrode trajectories) in 41 Parkinson’s disease patients. We modeled the signal and estimated the contribution of nearby/independent vs. remote/common activity in each recording configuration and area. Monopolar micro- and macroelectrode recordings detect field potentials that are considerably affected by common (probably cortical) activity. However, bipolar macroelectrode recordings inside the subthalamic nucleus can detect locally generated potentials. These results are confirmed by high correspondence between the model predictions and actual correlation of neuronal activity recorded by electrode pairs. Differential bipolar macroelectrode subthalamic field potentials can overcome volume conductance effects and reflect locally generated neuronal activity. Bipolar macroelectrode local field potential recordings might be used as a biological marker of normal and pathological brain functions for future electrophysiological studies and navigation systems as well as for closed-loop deep brain stimulation paradigms. NEW & NOTEWORTHY Our results integrate a new method for human subthalamic recordings with a development of an advanced mathematical model. We found that while monopolar microelectrode and macroelectrode recordings detect field potentials that are considerably affected by common (probably cortical) activity, bipolar macroelectrode recordings inside the subthalamic nucleus (STN) detect locally generated potentials that are significantly different than those recorded outside the STN. Differential bipolar subthalamic field potentials can be used in navigation and closed-loop deep brain stimulation paradigms. PMID:28202569

Simultaneous detection of P300 and steady-state visually evoked potentials for hybrid brain-computer interface.

PubMed

Combaz, Adrien; Van Hulle, Marc M

2015-01-01

We study the feasibility of a hybrid Brain-Computer Interface (BCI) combining simultaneous visual oddball and Steady-State Visually Evoked Potential (SSVEP) paradigms, where both types of stimuli are superimposed on a computer screen. Potentially, such a combination could result in a system being able to operate faster than a purely P300-based BCI and encode more targets than a purely SSVEP-based BCI. We analyse the interactions between the brain responses of the two paradigms, and assess the possibility to detect simultaneously the brain activity evoked by both paradigms, in a series of 3 experiments where EEG data are analysed offline. Despite differences in the shape of the P300 response between pure oddball and hybrid condition, we observe that the classification accuracy of this P300 response is not affected by the SSVEP stimulation. We do not observe either any effect of the oddball stimulation on the power of the SSVEP response in the frequency of stimulation. Finally results from the last experiment show the possibility of detecting both types of brain responses simultaneously and suggest not only the feasibility of such hybrid BCI but also a gain over pure oddball- and pure SSVEP-based BCIs in terms of communication rate.

Oxaloacetate decreases the infarct size and attenuates the reduction in evoked responses after photothrombotic focal ischemia in the rat cortex.

PubMed

Nagy, David; Marosi, Mate; Kis, Zsolt; Farkas, Tamas; Rakos, Gabriella; Vecsei, Laszlo; Teichberg, Vivian I; Toldi, Jozsef

2009-09-01

A traumatic brain injury or a focal brain lesion is followed by acute excitotoxicity caused by the presence of abnormally high glutamate (Glu) levels in the cerebrospinal and interstitial fluids. It has recently been demonstrated that this excess Glu in the brain can be eliminated into the blood following the intravenous administration of oxaloacetate (OxAc), which, by scavenging the blood Glu, induces an enhanced and neuroprotective brain-to-blood Glu efflux. In this study, we subjected rats to a photothrombotic lesion and treated them after the illumination with a single 30-min-long administration of OxAc (1.2 mg/100 g, i.v.). Following induction of the lesion, we measured the infarct size and the amplitudes of the somatosensory evoked potentials (SEPs) as recorded from the skull surface. The photothrombotic lesion resulted in appreciably decreased amplitudes of the evoked potentials, but OxAc administration significantly attenuated this reduction, and also the infarct size assessed histologically. We suggest that the neuroprotective effects of OxAc are due to its blood Glu-scavenging activity, which, by increasing the brain-to-blood Glu efflux, reduces the excess Glu responsible for the anatomical and functional correlates of the ischemia, as evaluated by electrophysiological evoked potential (EP) measurements.

Effects of nanoparticle zinc oxide on emotional behavior and trace elements homeostasis in rat brain.

PubMed

Amara, Salem; Slama, Imen Ben; Omri, Karim; El Ghoul, Jaber; El Mir, Lassaad; Rhouma, Khemais Ben; Abdelmelek, Hafedh; Sakly, Mohsen

2015-12-01

Over recent years, nanotoxicology and the potential effects on human body have grown in significance, the potential influences of nanosized materials on the central nervous system have received more attention. The aim of this study was to determine whether zinc oxide (ZnO) nanoparticles (NPs) exposure cause alterations in emotional behavior and trace elements homeostasis in rat brain. Rats were treated by intraperitoneal injection of ZnO NPs (20-30 nm) at a dose of 25 mg/kg body weight. Sub -: acute ZnO NPs treatment induced no significant increase in the zinc content in the homogenate brain. Statistically significant decreases in iron and calcium concentrations were found in rat brain tissue compared to control. However, sodium and potassium contents remained unchanged. Also, there were no significant changes in the body weight and the coefficient of brain. In the present study, the anxiety-related behavior was evaluated using the plus-maze test. ZnO NPs treatment modulates slightly the exploratory behaviors of rats. However, no significant differences were observed in the anxious index between ZnO NP-treated rats and the control group (p > 0.05). Interestingly, our results demonstrated minimal effects of ZnO NPs on emotional behavior of animals, but there was a possible alteration in trace elements homeostasis in rat brain. © The Author(s) 2012.

A methodological approach to studying resilience mechanisms: demonstration of utility in age and Alzheimer's disease-related brain pathology.

PubMed

Wolf, Dominik; Fischer, Florian Udo; Fellgiebel, Andreas

2018-05-01

The present work aims at providing a methodological approach for the investigation of resilience factors and mechanisms in normal aging, Alzheimer's disease (AD) and other neurodegenerative disorders. By expanding and re-conceptualizing traditional regression approaches, we propose an approach that not only aims at identifying potential resilience factors but also allows for a differentiation between general and dynamic resilience factors in terms of their association with pathology. Dynamic resilience factors are characterized by an increasing relevance with increasing levels of pathology, while the relevance of general resilience factors is independent of the amount of pathology. Utility of the approach is demonstrated in age and AD-related brain pathology by investigating widely accepted resilience factors, including education and brain volume. Moreover, the approach is used to test hippocampal volume as potential resilience factor. Education and brain volume could be identified as general resilience factors against age and AD-related pathology. Beyond that, analyses highlighted that hippocampal volume may not only be disease target but also serve as a potential resilience factor in age and AD-related pathology, particularly at higher levels of tau-pathology (i.e. dynamic resilience factor). Given its unspecific and superordinate nature the approach is suitable for the investigation of a wide range of potential resilience factors in normal aging, AD and other neurodegenerative disorders. Consequently, it may find a wide application and thereby promote the comparability between studies.

Task-Based Neurofeedback Training: A Novel Approach Toward Training Executive Functions

PubMed Central

Hosseini, SM Hadi; Pritchard-Berman, Mika; Sosa, Natasha; Ceja, Angelica; Kesler, Shelli R.

2016-01-01

Cognitive training is an emergent approach to improve cognitive functions in various neurodevelopmental and neurodegenerative diseases. However, current training programs can be relatively lengthy, making adherence potentially difficult for patients with cognitive difficulties. Previous studies suggest that providing individuals with real-time feedback about the level of brain activity (neurofeedback) can potentially help them learn to control the activation of specific brain regions. In the present study, we developed a novel task-based neurofeedback training paradigm that benefits from the effects of neurofeedback in parallel with computerized training. We focused on executive function training given its core involvement in various developmental and neurodegenerative diseases. Near-infrared spectroscopy (NIRS) was employed for providing neurofeedback by measuring changes in oxygenated hemoglobin in the prefrontal cortex. Of the twenty healthy adult participants, ten received real neurofeedback (NFB) on prefrontal activity during cognitive training, and ten were presented with sham feedback (SHAM). Compared with SHAM, the NFB group showed significantly improved executive function performance including measures of working memory after four sessions of training (100 minutes total). The NFB group also showed significantly reduced training-related brain activity in the executive function network including right middle frontal and inferior frontal regions compared with SHAM. Our data suggest that providing neurofeedback along with cognitive training can enhance executive function after a relatively short period of training. Similar designs could potentially be used for patient populations with known neuropathology, potentially helping them to boost/recover the activity in the affected brain regions. PMID:27015711

An in depth view of avian sleep.

PubMed

Beckers, Gabriël J L; Rattenborg, Niels C

2015-03-01

Brain rhythms occurring during sleep are implicated in processing information acquired during wakefulness, but this phenomenon has almost exclusively been studied in mammals. In this review we discuss the potential value of utilizing birds to elucidate the functions and underlying mechanisms of such brain rhythms. Birds are of particular interest from a comparative perspective because even though neurons in the avian brain homologous to mammalian neocortical neurons are arranged in a nuclear, rather than a laminar manner, the avian brain generates mammalian-like sleep-states and associated brain rhythms. Nonetheless, until recently, this nuclear organization also posed technical challenges, as the standard surface EEG recording methods used to study the neocortex provide only a superficial view of the sleeping avian brain. The recent development of high-density multielectrode recording methods now provides access to sleep-related brain activity occurring deep in the avian brain. Finally, we discuss how intracerebral electrical imaging based on this technique can be used to elucidate the systems-level processing of hippocampal-dependent and imprinting memories in birds. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cobalt-55 positron emission tomography in traumatic brain injury: a pilot study.

PubMed Central

Jansen, H M; van der Naalt, J; van Zomeren, A H; Paans, A M; Veenma-van der Duin, L; Hew, J M; Pruim, J; Minderhoud, J M; Korf, J

1996-01-01

Traumatic brain injury is usually assessed with the Glasgow coma scale (GCS), CT, or MRI. After such injury, the injured brain tissue is characterised by calcium mediated neuronal damage and inflammation. Positron emission tomography with the isotope cobalt-55 (Co-PET) as a calcium tracer enables imaging of affected tissue in traumatic brain injury. The aim was to determine whether additional information can be gained by Co-PET in the diagnosis of moderate traumatic brain injury and to assess any prognostic value of Co-PET. Five patients with recent moderately severe traumatic brain injury were studied. CT was performed on the day of admission, EEG within one week, and MRI and Co-PET within four weeks of injury. Clinical assessment included neurological examination, GCS, neuropsychological testing, and Glasgow outcome scale (GOS) after one year. Co-PET showed focal uptake that extended beyond the morphological abnormalities shown by MRI and CT, in brain regions that were actually diagnosed with EEG. Thus Co-PET is potentially useful for diagnostic localisation of both structural and functional abnormalities in moderate traumatic brain injury. Images PMID:8708661

Evaluating predisposition and training in shaping the musician's brain: the need for a developmental perspective.

PubMed

Zuk, Jennifer; Gaab, Nadine

2018-05-24

The study of music training as a model for structural plasticity has evolved significantly over the past 15 years. Neuroimaging studies have identified characteristic structural brain alterations in musicians compared to nonmusicians in school-age children and adults, using primarily cross-sectional designs. Despite this emerging evidence and advances in pediatric neuroimaging techniques, hardly any studies have examined brain development in early childhood (before age 8) in association with musical training, and longitudinal studies starting in infancy or preschool are particularly scarce. Consequently, it remains unclear whether the characteristic "musician brain" is solely the result of musical training, or whether certain predispositions may have an impact on its development. Moving toward a developmental perspective, the present review considers various factors that may contribute to early brain structure prior to the onset of formal musical training. This review introduces a model for potential neurobiological pathways leading to the characteristic "musician brain," which involves a developmental interaction between predisposition and its temporal dynamics, environmental experience, and training-induced plasticity. This perspective illuminates the importance of studying the brain structure associated with musical training through a developmental lens, and the need for longitudinal studies in early childhood to advance our understanding of music training-induced structural plasticity. © 2018 New York Academy of Sciences.

Robotics, stem cells, and brain-computer interfaces in rehabilitation and recovery from stroke: updates and advances.

PubMed

Boninger, Michael L; Wechsler, Lawrence R; Stein, Joel

2014-11-01

The aim of this study was to describe the current state and latest advances in robotics, stem cells, and brain-computer interfaces in rehabilitation and recovery for stroke. The authors of this summary recently reviewed this work as part of a national presentation. The article represents the information included in each area. Each area has seen great advances and challenges as products move to market and experiments are ongoing. Robotics, stem cells, and brain-computer interfaces all have tremendous potential to reduce disability and lead to better outcomes for patients with stroke. Continued research and investment will be needed as the field moves forward. With this investment, the potential for recovery of function is likely substantial.

A review on neuroimaging studies of genetic and environmental influences on early brain development.

PubMed

Gao, Wei; Grewen, Karen; Knickmeyer, Rebecca C; Qiu, Anqi; Salzwedel, Andrew; Lin, Weili; Gilmore, John H

2018-04-16

The past decades witnessed a surge of interest in neuroimaging study of normal and abnormal early brain development. Structural and functional studies of normal early brain development revealed massive structural maturation as well as sequential, coordinated, and hierarchical emergence of functional networks during the infancy period, providing a great foundation for the investigation of abnormal early brain development mechanisms. Indeed, studies of altered brain development associated with either genetic or environmental risks emerged and thrived. In this paper, we will review selected studies of genetic and environmental risks that have been relatively more extensively investigated-familial risks, candidate risk genes, and genome-wide association studies (GWAS) on the genetic side; maternal mood disorders and prenatal drug exposures on the environmental side. Emerging studies on environment-gene interactions will also be reviewed. Our goal was not to perform an exhaustive review of all studies in the field but to leverage some representative ones to summarize the current state, point out potential limitations, and elicit discussions on important future directions. Copyright © 2018 Elsevier Inc. All rights reserved.

Comparative Analytical Study of Evoked and Event Related Potentials as Correlates of Cognitive Processes

DTIC Science & Technology

1990-07-16

lower brain levels, probably precognitive , suggesting the need to distinguish the components in humans that depend on cognition from those that do...definition of the stimulus regime and that much of this response occurs at lower brain levels, probably precognitive , suggesting the need to distinguish the

Mismatch Negativity Elicited by Tones and Speech Sounds: Changed Topographical Distribution in Aphasia

ERIC Educational Resources Information Center

Becker, Frank; Reinvang, Ivar

2007-01-01

This study used the event-related brain potential mismatch negativity (MMN) to investigate preconscious discrimination of harmonically rich tones (differing in duration) and consonant-vowel syllables (differing in the initial consonant) in aphasia. Eighteen Norwegian aphasic patients, examined on average 3 months after brain injury, were compared…

RELATIONSHIP BETWEEN BRAIN AND OVARY AROMATASE ACTIVITY AND ISOFORM-SPECIFIC AROMATASE MRNA EXPRESSION IN THE FATHEAD MINNOW (PIMEPHALES PROMELAS)

EPA Science Inventory

There is growing evidence that some chemicals present in the environment have the capacity to inhibit, or potentially induce, aromatase activity. This study compared aromatase activities and isoform-specific mRNA expression in brain and ovary tissue from non-exposed fathead min...

RELATIONSHIP BETWEEN BRAIN AND OVARY AROMATASE ACTIVITY AND ISOFORM-SPECIFIC AROMATASE MRNA EXPRESSION IN THE FATHEAD MINNOW (PIMEPHALES PROMELAS) - JOURNAL ARTICLE

EPA Science Inventory

There is growing evidence that some chemicals present in the environment have the capacity to inhibit, or potentially induce, aromatase activity. This study compared aromatase activities and isoform-specific mRNA expression in brain and ovary tissue from non-exposed fathead minn...

The Feasibility and Potential Impact of Brain Training Games on Cognitive and Emotional Functioning in Middle-Aged Adults

PubMed Central

Curtis, Ashley F.; Branscombe-Caird, Laura M.; Comrie, Janna K.; Murtha, Susan J.E.

2018-01-01

Abstract Objectives:To investigate whether a commercially available brain training program is feasible to use with a middle-aged population and has a potential impact on cognition and emotional well-being (proof of concept). Method: Fourteen participants (ages 46–55) completed two 6-week training conditions using a crossover (counterbalanced) design: (1) experimental brain training condition and (2) active control “find answers to trivia questions online” condition. A comprehensive neurocognitive battery and a self-report measure of depression and anxiety were administered at baseline (first time point, before training) and after completing each training condition (second time point at 6 weeks, and third time point at 12 weeks). Cognitive composite scores were calculated for participants at each time point. Results: Study completion and protocol adherence demonstrated good feasibility of this brain training protocol in healthy middle-aged adults. Exploratory analyses suggested that brain training was associated with neurocognitive improvements related to executive attention, as well as improvements in mood. Conclusion: Overall, our findings suggest that brain training programs are feasible in middle-aged cohorts. We propose that brain training games may be linked to improvements in executive attention and affect by promoting cognitive self-efficacy in middle-aged adults. PMID:29189046

Mangiferin attenuates blast-induced traumatic brain injury via inhibiting NLRP3 inflammasome.

PubMed

Fan, Kaihua; Ma, Jie; Xiao, Wenjing; Chen, Jingmin; Wu, Juan; Ren, Jiandong; Hou, Jun; Hu, Yonghe; Gu, Jianwen; Yu, Botao

2017-06-01

There is growing evidence that Mangiferin possess therapeutic benefit during neuroinflammation on various brain injury models due to its anti-inflammatory properties. It is reported that inflammatory plays a crucial role in the pathogenesis of secondary injury induced by the blast-induced traumatic brain injury (bTBI). However, the role of mangiferin in bTBI is yet to be studied. In our study, the potential effect of mangiferin in the duration of bTBI was examined first. Fortunately, the amelioration of cerebral cortex damage was found in rats suffering bTBI after mangiferin administration. Furthermore, the detail mechanism of mangiferin's beneficial actions in bTBI was also studied. The results revealed that mangiferin might alleviate brain damage in rats with bTBI by inhibiting the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome activation, which was accompanied by mangiferin's inhibition of oxidative stress and pro-inflammatory cytokines production. Therefore, this research allows us to speculate that, for first time, NLRP3 is involved in the anti-inflammatory effect of mangiferin in the cerebral cortex, and mangiferin could be a potential therapy drug for bTBI. Copyright © 2017 Elsevier B.V. All rights reserved.

Developments in brain-machine interfaces from the perspective of robotics.

PubMed

Kim, Hyun K; Park, Shinsuk; Srinivasan, Mandayam A

2009-04-01

Many patients suffer from the loss of motor skills, resulting from traumatic brain and spinal cord injuries, stroke, and many other disabling conditions. Thanks to technological advances in measuring and decoding the electrical activity of cortical neurons, brain-machine interfaces (BMI) have become a promising technology that can aid paralyzed individuals. In recent studies on BMI, robotic manipulators have demonstrated their potential as neuroprostheses. Restoring motor skills through robot manipulators controlled by brain signals may improve the quality of life of people with disability. This article reviews current robotic technologies that are relevant to BMI and suggests strategies that could improve the effectiveness of a brain-operated neuroprosthesis through robotics.

Pedophilic brain potential responses to adult erotic stimuli.

PubMed

Knott, Verner; Impey, Danielle; Fisher, Derek; Delpero, Emily; Fedoroff, Paul

2016-02-01

Cognitive mechanisms associated with the relative lack of sexual interest in adults by pedophiles are poorly understood and may benefit from investigations examining how the brain processes adult erotic stimuli. The current study used event-related brain potentials (ERP) to investigate the time course of the explicit processing of erotic, emotional, and neutral pictures in 22 pedophilic patients and 22 healthy controls. Consistent with previous studies, early latency anterior ERP components were highly selective for erotic pictures. Although the ERPs elicited by emotional stimuli were similar in patients and controls, an early frontal positive (P2) component starting as early as 185 ms was significantly attenuated and slow to onset in pedophilia, and correlated with a clinical measure of cognitive distortions. Failure of rapid attentional capture by erotic stimuli suggests a relative reduction in early processing in pedophilic patients which may be associated with relatively diminished sexual interest in adults. Copyright © 2016. Published by Elsevier B.V.

Genetic variants in Alzheimer disease – molecular and brain network approaches

PubMed Central

Gaiteri, Chris; Mostafavi, Sara; Honey, Christopher; De Jager, Philip L.; Bennett, David A.

2016-01-01

Genetic studies in late-onset Alzheimer disease (LOAD) are aimed at identifying core disease mechanisms and providing potential biomarkers and drug candidates to improve clinical care for AD. However, due to the complexity of LOAD, including pathological heterogeneity and disease polygenicity, extracting actionable guidance from LOAD genetics has been challenging. Past attempts to summarize the effects of LOAD-associated genetic variants have used pathway analysis and collections of small-scale experiments to hypothesize functional convergence across several variants. In this review, we discuss how the study of molecular, cellular and brain networks provides additional information on the effect of LOAD-associated genetic variants. We then discuss emerging combinations of omic data types in multiscale models, which provide a more comprehensive representation of the effect of LOAD-associated genetic variants at multiple biophysical scales. Further, we highlight the clinical potential of mechanistically coupling genetic variants and disease phenotypes with multiscale brain models. PMID:27282653

Potentiated antibodies to mu-opiate receptors: effect on integrative activity of the brain.

PubMed

Geiko, V V; Vorob'eva, T M; Berchenko, O G; Epstein, O I

2003-01-01

The effect of homeopathically potentiated antibodies to mu-receptors (10(-100) wt %) on integrative activity of rat brain was studied using the models of self-stimulation of the lateral hypothalamus and convulsions produced by electric current. Electric current was delivered through electrodes implanted into the ventromedial hypothalamus. Single treatment with potentiated antibodies to mu-receptors increased the rate of self-stimulation and decreased the threshold of convulsive seizures. Administration of these antibodies for 7 days led to further activation of the positive reinforcement system and decrease in seizure thresholds. Distilled water did not change the rate of self-stimulation and seizure threshold.

The number of involved extracranial organs: a new predictor of survival in breast cancer patients with brain metastasis.

PubMed

Gerdan, Lavinia; Segedin, Barbara; Nagy, Viorica; Khoa, Mai T; Trang, Ngo T; Schild, Steven E; Rades, Dirk

2013-10-01

This study was performed to investigate the potential impact of the number of involved extracranial organs on survival in patients with brain metastasis from breast cancer. The data of 196 patients treated with whole-brain radiotherapy (WBRT) alone for brain metastases from breast cancer were retrospectively analyzed. Six potential prognostic factors were evaluated for associations with survival. These factors included WBRT regimen, age, Karnofsky performance score (KPS), number of brain metastases, interval from breast cancer diagnosis to WBRT, and the number of involved extracranial organs. The 6-month survival rates of patients with involvement of 0, 1, 2, 3 and ≥4 extracranial organs were 59%, 49%, 26%, 26% and 13%, respectively, and the 12-month survival rates were 45%, 36%, 17%, 17% and 13%, respectively (p<0.001). On multivariate analysis, the number of involved extracranial organs (risk ratio 1.17; 95%-confidence interval 1.02-1.35; p=0.028) maintained significance, as did KPS (p<0.001), but not age (p=0.27). The number of involved extracranial organs is an independent prognostic factor of survival in patients with brain metastasis from breast cancer. Copyright © 2013 Elsevier B.V. All rights reserved.

MRS of brain metabolite levels demonstrates the ability of scavenging of excess brain glutamate to protect against nerve agent induced seizures.

PubMed

Ruban, Angela; Biton, Inbal E; Markovich, Arik; Mirelman, David

2015-02-02

This study describes the use of in vivo magnetic resonance spectrocopy (MRS) to monitor brain glutamate and lactate levels in a paraoxon (PO) intoxication model. Our results show that the administration of recombinant glutamate-oxaloacetate transaminase (rGOT) in combination with oxaloacetate (OxAc) significantly reduces the brain-accumulated levels of glutamate. Previously we have shown that the treatment causes a rapid decrease of blood glutamate levels and creates a gradient between the brain and blood glutamate levels which leads to the efflux of excess brain glutamate into the blood stream thereby reducing its potential to cause neurological damage. The fact that this treatment significantly decreased the brain glutamate and lactate levels following PO intoxication suggests that it could become a new effective neuroprotective agent.

Dose Escalation of Whole-Brain Radiotherapy for Brain Metastases From Melanoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rades, Dirk, E-mail: Rades.Dirk@gmx.ne; Heisterkamp, Christine; Huttenlocher, Stefan

2010-06-01

Purpose: The majority of patients with brain metastases from melanoma receive whole-brain radiotherapy (WBRT). However, the results are poor. Hypofractionation regimens failed to improve the outcome of these patients. This study investigates a potential benefit from escalation of the WBRT dose beyond the 'standard' regimen 30 Gy in 10 fractions (10x3 Gy). Methods and Materials: Data from 51 melanoma patients receiving WBRT alone were retrospectively analyzed. A dosage of 10x3 Gy (n = 33) was compared with higher doses including 40 Gy/20 fractions (n = 11) and 45 Gy/15 fractions (n = 7) for survival (OS) and local (intracerebral) controlmore » (LC). Additional potential prognostic factors were evaluated: age, gender, performance status, number of metastases, extracerebral metastases, and recursive partitioning analysis (RPA) class. Results: At 6 months, OS rates were 27% after 10x3 Gy and 50% after higher doses (p = 0.009). The OS rates at 12 months were 4% and 20%. On multivariate analysis, higher WBRT doses (p = 0.010), fewer than four brain metastases (p = 0.012), no extracerebral metastases (p = 0.006), and RPA class 1 (p = 0.005) were associated with improved OS. The LC rates at 6 months were 23% after 10x3 Gy and 50% after higher doses (p = 0.021). The LC rates at 12 months were 0% and 13%. On multivariate analysis, higher WBRT doses (p = 0.020) and fewer than brain metastases (p = 0.002) were associated with better LC. Conclusions: Given the limitations of a retrospective study, the findings suggest that patients with brain metastases from melanoma receiving WBRT alone may benefit from dose escalation beyond 10x3 Gy. The hypothesis generated by this study must be confirmed in a randomized trial stratifying for significant prognostic factors.« less

Targeting the Brain with a Neuroprotective Omega-3 Fatty Acid to Enhance Neurogenesis in Hypoxic Condition in Culture.

PubMed

Lo Van, Amanda; Sakayori, Nobuyuki; Hachem, Mayssa; Belkouch, Mounir; Picq, Madeleine; Fourmaux, Baptiste; Lagarde, Michel; Osumi, Noriko; Bernoud-Hubac, Nathalie

2018-06-01

Docosahexaenoic acid (DHA, 22:6n-3) is an essential omega-3 polyunsaturated fatty acid (PUFA) that is required for proper brain development and cerebral functions. While DHA deficiency in the brain was shown to be linked to the emergence of cerebral diseases, a dietary intake of omega-3 PUFA could prevent or attenuate neurologic disturbances linked with aging or neurodegenerative diseases. In this context, targeting the brain with DHA might offer great promise in developing new therapeutics for neurodegenerative diseases. We previously synthesized a stabilized form of DHA-containing lysophosphatidylcholine a major vector of DHA transportation to the brain, which is 1-acetyl,2-docoshexaenoyl-glycerophosphocholine, named AceDoPC®. Injection of AceDoPC® or DHA after experimental ischemic stroke showed that both molecules had neuroprotective effects but AceDoPC® was the most potent. This study aims to investigate the beneficial effects of DHA either unesterified or esterified within AceDoPC® on a model of neurogenesis in vitro, under physiological or pathological conditions. The effect of protectin DX (PDX, a double lipoxygenase product of DHA) was also tested. We cultured neural stem progenitor cells (NSPCs) derived from the adult mouse brain under normal or hypoxigenic (ischemic) conditions in vitro. Neurogenesis study of cell cultures with AceDoPC® showed enhanced neurogenesis compared to addition of unesterified DHA, PDX, or vehicle control, especially under pathological conditions. Our studies of the potential mechanisms involved in neuroprotection hinted that AceDoPC® neuroprotective and regenerative effects might be due in part to its anti-oxidative effects. These results indicate the potential for novel therapeutics against stroke that target the brain.

Chronic ethanol increases systemic TLR3 agonist-induced neuroinflammation and neurodegeneration

PubMed Central

2012-01-01

Background Increasing evidence links systemic inflammation to neuroinflammation and neurodegeneration. We previously found that systemic endotoxin, a TLR4 agonist or TNFα, increased blood TNFα that entered the brain activating microglia and persistent neuroinflammation. Further, we found that models of ethanol binge drinking sensitized blood and brain proinflammatory responses. We hypothesized that blood cytokines contribute to the magnitude of neuroinflammation and that ethanol primes proinflammatory responses. Here, we investigate the effects of chronic ethanol on neuroinflammation and neurodegeneration triggered by toll-like receptor 3 (TLR3) agonist poly I:C. Methods Polyinosine-polycytidylic acid (poly I:C) was used to induce inflammatory responses when sensitized with D-galactosamine (D-GalN). Male C57BL/6 mice were treated with water or ethanol (5 g/kg/day, i.g., 10 days) or poly I:C (250 μg/kg, i.p.) alone or sequentially 24 hours after ethanol exposure. Cytokines, chemokines, microglial morphology, NADPH oxidase (NOX), reactive oxygen species (ROS), high-mobility group box 1 (HMGB1), TLR3 and cell death markers were examined using real-time PCR, ELISA, immunohistochemistry and hydroethidine histochemistry. Results Poly I:C increased blood and brain TNFα that peaked at three hours. Blood levels returned within one day, whereas brain levels remained elevated for at least three days. Escalating blood and brain proinflammatory responses were found with ethanol, poly I:C, and ethanol-poly I:C treatment. Ethanol pretreatment potentiated poly I:C-induced brain TNFα (345%), IL-1β (331%), IL-6 (255%), and MCP-1(190%). Increased levels of brain cytokines coincided with increased microglial activation, NOX gp91phox, superoxide and markers of neurodegeneration (activated caspase-3 and Fluoro-Jade B). Ethanol potentiation of poly I:C was associated with ethanol-increased expression of TLR3 and endogenous agonist HMGB1 in the brain. Minocycline and naltrexone blocked microglial activation and neurodegeneration. Conclusions Chronic ethanol potentiates poly I:C blood and brain proinflammatory responses. Poly I:C neuroinflammation persists after systemic responses subside. Increases in blood TNFα, IL-1β, IL-6, and MCP-1 parallel brain responses consistent with blood cytokines contributing to the magnitude of neuroinflammation. Ethanol potentiation of TLR3 agonist responses is consistent with priming microglia-monocytes and increased NOX, ROS, HMGB1-TLR3 and markers of neurodegeneration. These studies indicate that TLR3 agonists increase blood cytokines that contribute to neurodegeneration and that ethanol binge drinking potentiates these responses. PMID:22709825

Optical microangiography enabling visualization of change in meninges after traumatic brain injury in mice in vivo

NASA Astrophysics Data System (ADS)

Choi, Woo June; Qin, Wan; Qi, Xiaoli; Wang, Ruikang K.

2016-03-01

Traumatic brain injury (TBI) is a form of brain injury caused by sudden impact on brain by an external mechanical force. Following the damage caused at the moment of injury, TBI influences pathophysiology in the brain that takes place within the minutes or hours involving alterations in the brain tissue morphology, cerebral blood flow (CBF), and pressure within skull, which become important contributors to morbidity after TBI. While many studies for the TBI pathophysiology have been investigated with brain cortex, the effect of trauma on intracranial tissues has been poorly studied. Here, we report use of high-resolution optical microangiography (OMAG) to monitor the changes in cranial meninges beneath the skull of mouse after TBI. TBI is induced on a brain of anesthetized mouse by thinning the skull using a soft drill where a series of drilling exert mechanical stress on the brain through the skull, resulting in mild brain injury. Intracranial OMAG imaging of the injured mouse brain during post-TBI phase shows interesting pathophysiological findings in the meningeal layers such as widening of subdural space as well as vasodilation of subarachnoid vessels. These processes are acute and reversible within hours. The results indicate potential of OMAG to explore mechanism involved following TBI on small animals in vivo.

Pain measurement and brain activity: will neuroimages replace pain ratings?

PubMed

Robinson, Michael E; Staud, Roland; Price, Donald D

2013-04-01

Arguments made for the advantages of replacing pain ratings with brain-imaging data include assumptions that pain ratings are less reliable and objective and that brain image data would greatly benefit the measurement of treatment efficacy. None of these assumptions are supported by available evidence. Self-report of pain is predictable and does not necessarily reflect unreliability or error. Because pain is defined as an experience, magnitudes of its dimensions can be estimated by well-established methods, including those used to validate brain imaging of pain. Brain imaging helps to study pain mechanisms and might be used as proxy measures of pain in persons unable to provide verbal reports. Yet eliminating pain ratings or replacing them with neuroimaging data is misguided because brain images only help explain pain if they are used in conjunction with self-report. There is no objective readout mechanism of pain (pain thermometer) that is unaffected by psychological factors. Benefits from including neuroimaging data might include increased understanding of underlying neural mechanisms of treatment efficacy, discovery of new treatment vectors, and support of conclusions derived from self-report. However, neither brain imaging nor self-report data are privileged over the other. The assumption that treatment efficacy is hampered by self-report has not been shown; there is a plethora of treatment studies showing that self-report is sensitive to treatment. Dismissal of patients' self-reports (pain ratings) by brain-imaging data is potentially harmful. The aim of replacing self-report with brain-imaging data is misguided and has no scientific or philosophical foundation. Although brain imaging may offer considerable insight into the neural mechanisms of pain, including relevant causes and correlations, brain images cannot and should not replace self-report. Only the latter assesses the experience of pain, which is not identical to neural activity. Brain imaging may help to explain pain, but replacing self-report with brain-imaging data would be philosophically and scientifically misguided and potentially harmful to pain patients. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

Diagnostic segregation of human brain tumours using Fourier-transform infrared and/or Raman spectroscopy coupled with discriminant analysis†

PubMed Central

Gajjar, Ketan; Heppenstall, Lara D.; Pang, Weiyi; Ashton, Katherine M.; Trevisan, Júlio; Patel, Imran I.; Llabjani, Valon; Stringfellow, Helen F.; Martin-Hirsch, Pierre L.; Dawson, Timothy; Martin, Francis L.

2013-01-01

The most common initial treatment received by patients with a brain tumour is surgical removal of the growth. Precise histopathological diagnosis of brain tumours is to some extent subjective. Furthermore, currently available diagnostic imaging techniques to delineate the excision border during cytoreductive surgery lack the required spatial precision to aid surgeons. We set out to determine whether infrared (IR) and/or Raman spectroscopy combined with multivariate analysis could be applied to discriminate between normal brain tissue and different tumour types (meningioma, glioma and brain metastasis) based on the unique spectral “fingerprints” of their biochemical composition. Formalin-fixed paraffin-embedded tissue blocks of normal brain and different brain tumours were de-waxed, mounted on low-E slides and desiccated before being analyzed using attenuated total reflection Fourier-transform IR (ATR-FTIR) and Raman spectroscopy. ATR-FTIR spectroscopy showed a clear segregation between normal and different tumour subtypes. Discrimination of tumour classes was also apparent with Raman spectroscopy. Further analysis of spectral data revealed changes in brain biochemical structure associated with different tumours. Decreased tentatively-assigned lipid-to-protein ratio was associated with increased tumour progression. Alteration in cholesterol esters-to-phenylalanine ratio was evident in grade IV glioma and metastatic tumours. The current study indicates that IR and/or Raman spectroscopy have the potential to provide a novel diagnostic approach in the accurate diagnosis of brain tumours and have potential for application in intra-operative diagnosis. PMID:24098310

Targeted delivery of antibody-based therapeutic and imaging agents to CNS tumors: Crossing the blood-brain-barrier divide

PubMed Central

Chacko, Ann-Marie; Li, Chunsheng; Pryma, Daniel A.; Brem, Steven; Coukos, George; Muzykantov, Vladimir R.

2014-01-01

Introduction Brain tumors are inherently difficult to treat in large part due to the cellular blood-brain barriers (BBB) that limit the delivery of therapeutics to the tumor tissue from the systemic circulation. Virtually no large-molecules, including antibody-based proteins, can penetrate the BBB. With antibodies fast becoming attractive ligands for highly specific molecular targeting to tumor antigens, a variety of methods are being investigated to enhance the access of these agents to intracranial tumors for imaging or therapeutic applications. Areas covered This review describes the characteristics of the BBB and the vasculature in brain tumors, described as the blood-brain tumor barrier (BBTB). Antibodies targeted to molecular markers of CNS tumors will be highlighted, and current strategies for enhancing the delivery of antibodies across these cellular barriers into the brain parenchyma to the tumor will be discussed. Non-invasive imaging approaches to assess BBB/BBTB permeability and/or antibody targeting will be presented as a means of guiding the optimal delivery of targeted agents to brain tumors. Expert Opinion Pre-clinical and clinical studies highlight the potential of several approaches in increasing brain tumor delivery across the blood-brain barrier divide. However, each carries its own risks and challenges. There is tremendous potential in using neuroimaging strategies to assist in understanding and defining the challenges to translating and optimizing molecularly-targeted antibody delivery to CNS tumors to improve clinical outcomes. PMID:23751126

High occupancy of sigma-1 receptors in the human brain after single oral administration of fluvoxamine: a positron emission tomography study using [11C]SA4503.

PubMed

Ishikawa, Masatomo; Ishiwata, Kiichi; Ishii, Kenji; Kimura, Yuichi; Sakata, Muneyuki; Naganawa, Mika; Oda, Keiichi; Miyatake, Ryousuke; Fujisaki, Mihisa; Shimizu, Eiji; Shirayama, Yukihiko; Iyo, Masaomi; Hashimoto, Kenji

2007-10-15

Sigma-1 receptors might be implicated in the pathophysiology of psychiatric diseases, as well as in the mechanisms of action of some selective serotonin reuptake inhibitors (SSRIs). Among the several SSRIs, fluvoxamine has the highest affinity for sigma-1 receptors (Ki = 36 nM), whereas paroxetine shows low affinity (Ki = 1893 nM). The present study was undertaken to examine whether fluvoxamine binds to sigma-1 receptors in living human brain. A dynamic positron emission tomography (PET) data acquisition using the selective sigma-1 receptor ligand [(11)C]SA4503 was performed with arterial blood sampling to evaluate quantitatively the binding of [(11)C]SA4503 to sigma-1 receptors in 15 healthy male volunteers. Each subject had two PET scans before and after randomly receiving a single dose of either fluvoxamine (50, 100, 150, or 200 mg) or paroxetine (20 mg). The binding potential of [(11)C]SA4503 in 9 regions of the brain was calculated by a 2-tissue 3-compartment model. In addition, we examined the effects of functional polymorphisms of the sigma-1 receptor (SIGMAR1) gene on the binding potential of [(11)C]SA4503. Fluvoxamine bound to sigma-1 receptors in all brain regions in a dose-dependent manner, whereas paroxetine did not bind to sigma-1 receptors. However, there was no association between the SIGMAR1 gene polymorphism GC-241-240TT and binding potential. The study demonstrated that fluvoxamine bound to sigma-1 receptors in living human brain at therapeutic doses. These findings suggest that sigma-1 receptors may play an important role in the mechanism of action of fluvoxamine.

The effect of ingested sulfite on visual evoked potentials, lipid peroxidation, and antioxidant status of brain in normal and sulfite oxidase-deficient aged rats.

PubMed

Ozsoy, Ozlem; Aras, Sinem; Ozkan, Ayse; Parlak, Hande; Aslan, Mutay; Yargicoglu, Piraye; Agar, Aysel

2016-07-01

Sulfite, commonly used as a preservative in foods, beverages, and pharmaceuticals, is a very reactive and potentially toxic molecule which is detoxified by sulfite oxidase (SOX). Changes induced by aging may be exacerbated by exogenous chemicals like sulfite. The aim of this study was to investigate the effects of ingested sulfite on visual evoked potentials (VEPs) and brain antioxidant statuses by measuring superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities. Brain lipid oxidation status was also determined via thiobarbituric acid reactive substances (TBARS) in normal- and SOX-deficient aged rats. Rats do not mimic the sulfite responses seen in humans because of their relatively high SOX activity level. Therefore this study used SOX-deficient rats since they are more appropriate models for studying sulfite toxicity. Forty male Wistar rats aged 24 months were randomly assigned to four groups: control (C), sulfite (S), SOX-deficient (D) and SOX-deficient + sulfite (DS). SOX deficiency was established by feeding rats with low molybdenum (Mo) diet and adding 200 ppm tungsten (W) to their drinking water. Sulfite in the form of sodium metabisulfite (25 mg kg(-1) day(-1)) was given by gavage. Treatment continued for 6 weeks. At the end of the experimental period, flash VEPs were recorded. Hepatic SOX activity was measured to confirm SOX deficiency. SOX-deficient rats had an approximately 10-fold decrease in hepatic SOX activity compared with the normal rats. The activity of SOX in deficient rats was thus in the range of humans. There was no significant difference between control and treated groups in either latence or amplitude of VEP components. Brain SOD, CAT, and GPx activities and brain TBARS levels were similar in all experimental groups compared with the control group. Our results indicate that exogenous administration of sulfite does not affect VEP components and the antioxidant/oxidant status of aged rat brains. © The Author(s) 2014.

Steady-state visual evoked potential (SSVEP)-based communication: impact of harmonic frequency components

NASA Astrophysics Data System (ADS)

Müller-Putz, Gernot R.; Scherer, Reinhold; Brauneis, Christian; Pfurtscheller, Gert

2005-12-01

Brain-computer interfaces (BCIs) can be realized on the basis of steady-state evoked potentials (SSEPs). These types of brain signals resulting from repetitive stimulation have the same fundamental frequency as the stimulation but also include higher harmonics. This study investigated how the classification accuracy of a 4-class BCI system can be improved by incorporating visually evoked harmonic oscillations. The current study revealed that the use of three SSVEP harmonics yielded a significantly higher classification accuracy than was the case for one or two harmonics. During feedback experiments, the five subjects investigated reached a classification accuracy between 42.5% and 94.4%.

Steady-state visual evoked potential (SSVEP)-based communication: impact of harmonic frequency components.

PubMed

Müller-Putz, Gernot R; Scherer, Reinhold; Brauneis, Christian; Pfurtscheller, Gert

2005-12-01

Brain-computer interfaces (BCIs) can be realized on the basis of steady-state evoked potentials (SSEPs). These types of brain signals resulting from repetitive stimulation have the same fundamental frequency as the stimulation but also include higher harmonics. This study investigated how the classification accuracy of a 4-class BCI system can be improved by incorporating visually evoked harmonic oscillations. The current study revealed that the use of three SSVEP harmonics yielded a significantly higher classification accuracy than was the case for one or two harmonics. During feedback experiments, the five subjects investigated reached a classification accuracy between 42.5% and 94.4%.

The importance of scientific collecting and natural history museums for comparative neuroanatomy.

PubMed

Iwaniuk, Andrew N

2011-05-01

The comparative study of vertebrate brains is inherently dependent upon access to a sufficient number of species and specimens to perform meaningful comparisons. Although many studies rely on compiling published information, continued specimen collection, in addition to more extensive use of existing brain collections and natural history museums, are crucial for detailed neuroanatomical comparisons across species. This review highlights the importance of collecting species through a variety of means, details a marsupial brain collection, and stresses the potential of natural history museums as a resource for comparative neuroanatomy. By taking advantage of as many of these resources as possible, researchers can rapidly increase species coverage and generate a better understanding of how the brain evolves. © 2011 New York Academy of Sciences.

NeuroGrid: recording action potentials from the surface of the brain.

PubMed

Khodagholy, Dion; Gelinas, Jennifer N; Thesen, Thomas; Doyle, Werner; Devinsky, Orrin; Malliaras, George G; Buzsáki, György

2015-02-01

Recording from neural networks at the resolution of action potentials is critical for understanding how information is processed in the brain. Here, we address this challenge by developing an organic material-based, ultraconformable, biocompatible and scalable neural interface array (the 'NeuroGrid') that can record both local field potentials(LFPs) and action potentials from superficial cortical neurons without penetrating the brain surface. Spikes with features of interneurons and pyramidal cells were simultaneously acquired by multiple neighboring electrodes of the NeuroGrid, allowing for the isolation of putative single neurons in rats. Spiking activity demonstrated consistent phase modulation by ongoing brain oscillations and was stable in recordings exceeding 1 week's duration. We also recorded LFP-modulated spiking activity intraoperatively in patients undergoing epilepsy surgery. The NeuroGrid constitutes an effective method for large-scale, stable recording of neuronal spikes in concert with local population synaptic activity, enhancing comprehension of neural processes across spatiotemporal scales and potentially facilitating diagnosis and therapy for brain disorders.

Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior

PubMed Central

Leclercq, Sophie; Mian, Firoz M.; Stanisz, Andrew M.; Bindels, Laure B.; Cambier, Emmanuel; Ben-Amram, Hila; Koren, Omry; Forsythe, Paul; Bienenstock, John

2017-01-01

There is increasing concern about potential long-term effects of antibiotics on children's health. Epidemiological studies have revealed that early-life antibiotic exposure can increase the risk of developing immune and metabolic diseases, and rodent studies have shown that administration of high doses of antibiotics has long-term effects on brain neurochemistry and behaviour. Here we investigate whether low-dose penicillin in late pregnancy and early postnatal life induces long-term effects in the offspring of mice. We find that penicillin has lasting effects in both sexes on gut microbiota, increases cytokine expression in frontal cortex, modifies blood–brain barrier integrity and alters behaviour. The antibiotic-treated mice exhibit impaired anxiety-like and social behaviours, and display aggression. Concurrent supplementation with Lactobacillus rhamnosus JB-1 prevents some of these alterations. These results warrant further studies on the potential role of early-life antibiotic use in the development of neuropsychiatric disorders, and the possible attenuation of these by beneficial bacteria. PMID:28375200

Adaptive Capacity: An Evolutionary Neuroscience Model Linking Exercise, Cognition, and Brain Health.

PubMed

Raichlen, David A; Alexander, Gene E

2017-07-01

The field of cognitive neuroscience was transformed by the discovery that exercise induces neurogenesis in the adult brain, with the potential to improve brain health and stave off the effects of neurodegenerative disease. However, the basic mechanisms underlying exercise-brain connections are not well understood. We use an evolutionary neuroscience approach to develop the adaptive capacity model (ACM), detailing how and why physical activity improves brain function based on an energy-minimizing strategy. Building on studies showing a combined benefit of exercise and cognitive challenge to enhance neuroplasticity, our ACM addresses two fundamental questions: (i) what are the proximate and ultimate mechanisms underlying age-related brain atrophy, and (ii) how do lifestyle changes influence the trajectory of healthy and pathological aging? Copyright © 2017 Elsevier Ltd. All rights reserved.

Infant fMRI: A Model System for Cognitive Neuroscience.

PubMed

Ellis, Cameron T; Turk-Browne, Nicholas B

2018-05-01

Our understanding of the typical human brain has benefitted greatly from studying different kinds of brains and their associated behavioral repertoires, including animal models and neuropsychological patients. This same comparative perspective can be applied to early development - the environment, behavior, and brains of infants provide a model system for understanding how the mature brain works. This approach requires noninvasive methods for measuring brain function in awake, behaving infants. fMRI is becoming increasingly viable for this purpose, with the unique ability to precisely measure the entire brain, including both cortical and subcortical structures. Here we discuss potential lessons from infant fMRI for several domains of adult cognition and consider the challenges of conducting such research and how they might be mitigated. Copyright © 2018 Elsevier Ltd. All rights reserved.

Blood-brain barrier leakage after status epilepticus in rapamycin-treated rats II: Potential mechanisms.

PubMed

van Vliet, Erwin A; Otte, Willem M; Wadman, Wytse J; Aronica, Eleonora; Kooij, Gijs; de Vries, Helga E; Dijkhuizen, Rick M; Gorter, Jan A

2016-01-01

Blood-brain barrier (BBB) leakage may play a pro-epileptogenic role after status epilepticus. In the accompanying contrast-enhanced magnetic resonance imaging (CE-MRI) study we showed that the mammalian target of rapamycin (mTOR) inhibitor rapamycin reduced BBB leakage and seizure activity during the chronic epileptic phase. Given rapamycin's role in growth and immune response, the potential therapeutic effects of rapamycin after status epilepticus with emphasis on brain inflammation and brain vasculature were investigated. Seven weeks after kainic acid-induced status epilepticus, rats were perfusion fixed and (immuno)histochemistry was performed using several glial and vascular markers. In addition, an in vitro model for the human BBB was used to determine the effects of rapamycin on transendothelial electrical resistance as a measure for BBB integrity. (Immuno)histochemistry showed that local blood vessel density, activated microglia, and astrogliosis were reduced in rapamycin-treated rats compared to vehicle-treated rats. In vitro studies showed that rapamycin could attenuate TNFα-induced endothelial barrier breakdown. These data suggest that rapamycin improves BBB function during the chronic epileptic phase by a reduction of local brain inflammation and blood vessel density that can contribute to a milder form of epilepsy. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Default mode network as a potential biomarker of chemotherapy-related brain injury

PubMed Central

Kesler, Shelli R.

2014-01-01

Chronic medical conditions and/or their treatments may interact with aging to alter or even accelerate brain senescence. Adult onset cancer, for example, is a disease associated with advanced aging and emerging evidence suggests a profile of subtle but diffuse brain injury following cancer chemotherapy. Breast cancer is currently the primary model for studying these “chemobrain” effects. Given the widespread changes to brain structure and function as well as the common impairment of integrated cognitive skills observed following breast cancer chemotherapy, it is likely that large-scale brain networks are involved. Default mode network (DMN) is a strong candidate considering its preferential vulnerability to aging and sensitivity to toxicity and disease states. Additionally, chemotherapy is associated with several physiologic effects including increased inflammation and oxidative stress that are believed to elevate toxicity in the DMN. Biomarkers of DMN connectivity could aid in the development of treatments for chemotherapy-related cognitive decline. For example, certain nutritional interventions could potentially reduce the metabolic changes (e.g. amyloid beta toxicity) associated with DMN disruption. PMID:24913897

Docosahexaenoic acid Confers Neuroprotection in a Rat Model of Perinatal Hypoxia-ischemia potentiated by E. coli lipopolysaccharide-induced systemic inflammation

PubMed Central

BERMAN, Deborah R; LIU, YiQing; BARKS, John; MOZURKEWICH, Ellen

2010-01-01

Objective Lipopolysaccharide (LPS) pretreatment potentiates HI injury. We hypothesized that docosahexaenoic acid (DHA) pretreatment would improve function and reduce brain damage in this rat model of perinatal brain injury and inflammation. Study Design Seven-day-old Wistar rats were divided into 3 groups. One received intraperitoneal (IP) DHA 1 mg/kg and LPS 0.1mg/kg. The second received 25% Albumin and LPS. The third received normal saline (NS). Injections were given 2.5 hours prior to right carotid ligation, followed by 90 minutes 8% O2. Rats underwent sensorimotor testing and brain damage assessment on P14. Results DHA pretreatment improved forepaw placing compared to albumin/LPS. (Mean±SD successes/10 trials: 8.57±1.7 DHA/LPS vs 6.72±2.2 Albumin/LPS, p<.0009). There were no significant differences in brain damage among groups. Conclusions Inflammatory stimulation before HI resulted in poorer function than HI alone. Although DHA pretreatment had no impact on brain damage, it significantly improved function in neonatal rats exposed to LPS and HI. PMID:19254588

Cytokines and cytokine networks target neurons to modulate long-term potentiation.

PubMed

Prieto, G Aleph; Cotman, Carl W

2017-04-01

Cytokines play crucial roles in the communication between brain cells including neurons and glia, as well as in the brain-periphery interactions. In the brain, cytokines modulate long-term potentiation (LTP), a cellular correlate of memory. Whether cytokines regulate LTP by direct effects on neurons or by indirect mechanisms mediated by non-neuronal cells is poorly understood. Elucidating neuron-specific effects of cytokines has been challenging because most brain cells express cytokine receptors. Moreover, cytokines commonly increase the expression of multiple cytokines in their target cells, thus increasing the complexity of brain cytokine networks even after single-cytokine challenges. Here, we review evidence on both direct and indirect-mediated modulation of LTP by cytokines. We also describe novel approaches based on neuron- and synaptosome-enriched systems to identify cytokines able to directly modulate LTP, by targeting neurons and synapses. These approaches can test multiple samples in parallel, thus allowing the study of multiple cytokines simultaneously. Hence, a cytokine networks perspective coupled with neuron-specific analysis may contribute to delineation of maps of the modulation of LTP by cytokines. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cytokines and cytokine networks target neurons to modulate long-term potentiation

PubMed Central

Prieto, G. Aleph; Cotman, Carl W.

2017-01-01

Cytokines play crucial roles in the communication between brain cells including neurons and glia, as well as in the brain-periphery interactions. In the brain, cytokines modulate long-term potentiation (LTP), a cellular correlate of memory. Whether cytokines regulate LTP by direct effects on neurons or by indirect mechanisms mediated by non-neuronal cells is poorly understood. Elucidating neuron-specific effects of cytokines has been challenging because most brain cells express cytokine receptors. Moreover, cytokines commonly increase the expression of multiple cytokines in their target cells, thus increasing the complexity of brain cytokine networks even after single-cytokine challenges. Here, we review evidence on both direct and indirect-mediated modulation of LTP by cytokines. We also describe novel approaches based on neuron- and synaptosome-enriched systems to identify cytokines able to directly modulate LTP, by targeting neurons and synapses. These approaches can test multiple samples in parallel, thus allowing the study of multiple cytokines simultaneously. Hence, a cytokine networks perspective coupled with neuron-specific analysis may contribute to delineation of maps of the modulation of LTP by cytokines. PMID:28377062

The profile of potential organ and tissue donors.

PubMed

Moraes, Edvaldo Leal de; Silva, Leonardo Borges de Barros E; Moraes, Tatiana Cristine de; Paixão, Nair Cordeiro dos Santos da; Izumi, Nelly Miyuki Shinohara; Guarino, Aparecida de Jesus

2009-01-01

This study aimed to characterize donors according to gender, age group, cause of brain death; quantify donors with hypernatremia, hyperpotassemia and hypopotassemia; and get to know which organs were the most used in transplantations. This quantitative, descriptive, exploratory and retrospective study was performed at the Organ Procurement Organization of the University of São Paulo Medical School Hospital das Clínicas. Data from the medical records of 187 potential donors were analyzed. Cerebrovascular accidents represented 53.48% of all brain death causes, sodium and potassium disorders occurred in 82.36% of cases and 45.46% of the potential donors were between 41 and 60 years old. The results evidenced that natural death causes exceeded traumatic deaths, and that most donors presented sodium and potassium alterations, likely associated to inappropriate maintenance.

Asymmetry of Hemispheric Network Topology Reveals Dissociable Processes between Functional and Structural Brain Connectome in Community-Living Elders

PubMed Central

Sun, Yu; Li, Junhua; Suckling, John; Feng, Lei

2017-01-01

Human brain is structurally and functionally asymmetrical and the asymmetries of brain phenotypes have been shown to change in normal aging. Recent advances in graph theoretical analysis have showed topological lateralization between hemispheric networks in the human brain throughout the lifespan. Nevertheless, apparent discrepancies of hemispheric asymmetry were reported between the structural and functional brain networks, indicating the potentially complex asymmetry patterns between structural and functional networks in aging population. In this study, using multimodal neuroimaging (resting-state fMRI and structural diffusion tensor imaging), we investigated the characteristics of hemispheric network topology in 76 (male/female = 15/61, age = 70.08 ± 5.30 years) community-dwelling older adults. Hemispheric functional and structural brain networks were obtained for each participant. Graph theoretical approaches were then employed to estimate the hemispheric topological properties. We found that the optimal small-world properties were preserved in both structural and functional hemispheric networks in older adults. Moreover, a leftward asymmetry in both global and local levels were observed in structural brain networks in comparison with a symmetric pattern in functional brain network, suggesting a dissociable process of hemispheric asymmetry between structural and functional connectome in healthy older adults. Finally, the scores of hemispheric asymmetry in both structural and functional networks were associated with behavioral performance in various cognitive domains. Taken together, these findings provide new insights into the lateralized nature of multimodal brain connectivity, highlight the potentially complex relationship between structural and functional brain network alterations, and augment our understanding of asymmetric structural and functional specializations in normal aging. PMID:29209197

Biochemical changes related to hypoxia during cerebral aneurysm surgery: combined microdialysis and tissue oxygen monitoring: case report.

PubMed

Hutchinson, P J; Al-Rawi, P G; O'Connell, M T; Gupta, A K; Pickard, J D; Kirkpatrick, P J

2000-01-01

The objective of this study was to monitor brain metabolism on-line during aneurysm surgery, by combining the use of a multiparameter (brain tissue oxygen, brain carbon dioxide, pH, and temperature) sensor with microdialysis (extracellular glucose, lactate, pyruvate, and glutamate). The case illustrates the potential value of these techniques by demonstrating the effects of adverse physiological events on brain metabolism and the ability to assist in both intraoperative and postoperative decision-making. A 41-year-old woman presented with a World Federation of Neurological Surgeons Grade I subarachnoid hemorrhage. Angiography revealed a basilar artery aneurysm that was not amenable to coiling, so the aneurysm was clipped. Before the craniotomy was performed, a multiparameter sensor and a microdialysis catheter were inserted to monitor brain metabolism. During the operation, the brain oxygen level decreased, in relation to biochemical changes, including the reduction of extracellular glucose and pyruvate and the elevation of lactate and glutamate. These changes were reversible. However, when the craniotomy was closed, a second decrease in brain oxygen occurred in association with brain swelling, which immediately prompted a postoperative computed tomographic scan. The scan demonstrated acute hydrocephalus, requiring external ventricular drainage. The patient made a full recovery. The monitoring techniques influenced clinical decision-making in the treatment of this patient. On-line measurement of brain tissue gases and extracellular chemistry has the potential to assist in the perioperative and postoperative management of patients undergoing complex cerebrovascular surgery and to establish the effects of intervention on brain homeostasis.

First multiphoton tomography of brain in man

NASA Astrophysics Data System (ADS)

König, Karsten; Kantelhardt, Sven R.; Kalasauskas, Darius; Kim, Ella; Giese, Alf

2016-03-01

We report on the first two-photon in vivo brain tissue imaging study in man. High resolution in vivo histology by multiphoton tomography (MPT) including two-photon FLIM was performed in the operation theatre during neurosurgery to evaluate the feasibility to detect label-free tumor borders with subcellular resolution. This feasibility study demonstrates, that MPT has the potential to identify tumor borders on a cellular level in nearly real-time.

Technology in the Assessment of Learning Disability.

ERIC Educational Resources Information Center

Bigler, Erin D.; Lajiness-O'Neill, Renee; Howes, Nancy-Louise

1998-01-01

Reviews recent neuroradiologic and brain imaging techniques in the assessment of learning disability. Technologies reviewed include computerized tomography; magnetic resonance imaging; electrophysiological and metabolic imaging; computerized electroencepholographic studies of evoked potentials, event-related potentials, spectral analysis, and…

Oxidative modification of lipoic acid by HNE in Alzheimer disease brain.

PubMed

Hardas, Sarita S; Sultana, Rukhsana; Clark, Amy M; Beckett, Tina L; Szweda, Luke I; Murphy, M Paul; Butterfield, D Allan

2013-01-01

Alzheimer disease (AD) is an age-related neurodegenerative disease characterized by the presence of three pathological hallmarks: synapse loss, extracellular senile plaques (SP) and intracellular neurofibrillary tangles (NFTs). The major component of SP is amyloid β-peptide (Aβ), which has been shown to induce oxidative stress. The AD brain shows increased levels of lipid peroxidation products, including 4-hydroxy-2-nonenal (HNE). HNE can react covalently with Cys, His, or Lys residues on proteins, altering structure and function of the latter. In the present study we measured the levels of the HNE-modified lipoic acid in brain of subjects with AD and age-matched controls. Lipoic acid is a key co-factor for a number of proteins including pyruvate dehydrogenase and α-ketoglutarate dehydrogenase, key complexes for cellular energetics. We observed a significant decrease in the levels of HNE-lipoic acid in the AD brain compared to that of age-matched controls. To investigate this phenomenon further, the levels and activity of lipoamide dehydrogenase (LADH) were measured in AD and control brains. Additionally, LADH activities were measured after in-vitro HNE-treatment to mice brains. Both LADH levels and activities were found to be significantly reduced in AD brain compared to age-matched control. HNE-treatment also reduced the LADH activity in mice brain. These data are consistent with a two-hit hypothesis of AD: oxidative stress leads to lipid peroxidation that, in turn, causes oxidative dysfunction of key energy-related complexes in mitochondria, triggering neurodegeneration. This study is consonant with the notion that lipoic acid supplementation could be a potential treatment for the observed loss of cellular energetics in AD and potentiate the antioxidant defense system to prevent or delay the oxidative stress in and progression of this devastating dementing disorder.

P43/pro-EMAPII: A Potential Biomarker for Discriminating Traumatic Versus Ischemic Brain Injury

PubMed Central

Yao, Changping; Williams, Anthony J.; Ottens, Andrew K.; Lu, X.-C. May; Liu, Ming Cheng; Hayes, Ronald L.; Wang, Kevin K.; Tortella, Frank C.

2009-01-01

Abstract To gain additional insights into the pathogenic cellular and molecular mechanisms underlying different types of brain injury (e.g., trauma versus ischemia), recently attention has focused on the discovery and study of protein biomarkers. In previous studies, using a high-throughput immunoblotting (HTPI) technique, we reported changes in 29 out of 998 proteins following acute injuries to the rat brain (penetrating traumatic versus focal ischemic). Importantly, we discovered that one protein, endothelial monocyte-activating polypeptide II precursor (p43/pro-EMAPII), was differentially expressed between these two types of brain injury. Among other functions, p43/pro-EMAPII is a known pro-inflammatory cytokine involved in the progression of apoptotic cell death. Our current objective was to verify the changes in p43/pro-EMAPII expression, and to evaluate the potentially important implications that the differential regulation of this protein has on injury development. At multiple time points following either a penetrating ballistic-like brain injury (PBBI), or a transient middle cerebral artery occlusion (MCAo) brain injury, tissue samples (6–72 h), CSF samples (24 h), and blood samples (24 h) were collected from rats for analysis. Changes in protein expression were assessed by Western blot analysis and immunohistochemistry. Our results indicated that p43/pro-EMAPII was significantly increased in brain tissues, CSF, and plasma following PBBI, but decreased after MCAo injury compared to their respective sham control samples. This differential expression of p43/pro-EMAPII may be a useful injury-specific biomarker associated with the underlying pathologies of traumatic versus ischemic brain injury, and provide valuable information for directing injury-specific therapeutics. PMID:19317603

Brain networks modulated by subthalamic nucleus deep brain stimulation.

PubMed

Accolla, Ettore A; Herrojo Ruiz, Maria; Horn, Andreas; Schneider, Gerd-Helge; Schmitz-Hübsch, Tanja; Draganski, Bogdan; Kühn, Andrea A

2016-09-01

Deep brain stimulation of the subthalamic nucleus is an established treatment for the motor symptoms of Parkinson's disease. Given the frequent occurrence of stimulation-induced affective and cognitive adverse effects, a better understanding about the role of the subthalamic nucleus in non-motor functions is needed. The main goal of this study is to characterize anatomical circuits modulated by subthalamic deep brain stimulation, and infer about the inner organization of the nucleus in terms of motor and non-motor areas. Given its small size and anatomical intersubject variability, functional organization of the subthalamic nucleus is difficult to investigate in vivo with current methods. Here, we used local field potential recordings obtained from 10 patients with Parkinson's disease to identify a subthalamic area with an analogous electrophysiological signature, namely a predominant beta oscillatory activity. The spatial accuracy was improved by identifying a single contact per macroelectrode for its vicinity to the electrophysiological source of the beta oscillation. We then conducted whole brain probabilistic tractography seeding from the previously identified contacts, and further described connectivity modifications along the macroelectrode's main axis. The designated subthalamic 'beta' area projected predominantly to motor and premotor cortical regions additional to connections to limbic and associative areas. More ventral subthalamic areas showed predominant connectivity to medial temporal regions including amygdala and hippocampus. We interpret our findings as evidence for the convergence of different functional circuits within subthalamic nucleus' portions deemed to be appropriate as deep brain stimulation target to treat motor symptoms in Parkinson's disease. Potential clinical implications of our study are illustrated by an index case where deep brain stimulation of estimated predominant non-motor subthalamic nucleus induced hypomanic behaviour. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Neuronal inhibition and synaptic plasticity of basal ganglia neurons in Parkinson's disease

PubMed Central

Milosevic, Luka; Kalia, Suneil K; Hodaie, Mojgan; Lozano, Andres M; Fasano, Alfonso; Popovic, Milos R; Hutchison, William D

2018-01-01

Abstract Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson’s disease symptoms. The therapeutic benefits of deep brain stimulation are frequency-dependent, but the underlying physiological mechanisms remain unclear. To advance deep brain stimulation therapy an understanding of fundamental mechanisms is critical. The objectives of this study were to (i) compare the frequency-dependent effects on cell firing in subthalamic nucleus and substantia nigra pars reticulata; (ii) quantify frequency-dependent effects on short-term plasticity in substantia nigra pars reticulata; and (iii) investigate effects of continuous long-train high frequency stimulation (comparable to conventional deep brain stimulation) on synaptic plasticity. Two closely spaced (600 µm) microelectrodes were advanced into the subthalamic nucleus (n = 27) and substantia nigra pars reticulata (n = 14) of 22 patients undergoing deep brain stimulation surgery for Parkinson’s disease. Cell firing and evoked field potentials were recorded with one microelectrode during stimulation trains from the adjacent microelectrode across a range of frequencies (1–100 Hz, 100 µA, 0.3 ms, 50–60 pulses). Subthalamic firing attenuated with ≥20 Hz (P < 0.01) stimulation (silenced at 100 Hz), while substantia nigra pars reticulata decreased with ≥3 Hz (P < 0.05) (silenced at 50 Hz). Substantia nigra pars reticulata also exhibited a more prominent increase in transient silent period following stimulation. Patients with longer silent periods after 100 Hz stimulation in the subthalamic nucleus tended to have better clinical outcome after deep brain stimulation. At ≥30 Hz the first evoked field potential of the stimulation train in substantia nigra pars reticulata was potentiated (P < 0.05); however, the average amplitude of the subsequent potentials was rapidly attenuated (P < 0.01). This is suggestive of synaptic facilitation followed by rapid depression. Paired pulse ratios calculated at the beginning of the train revealed that 20 Hz (P < 0.05) was the minimum frequency required to induce synaptic depression. Lastly, the average amplitude of evoked field potentials during 1 Hz pulses showed significant inhibitory synaptic potentiation after long-train high frequency stimulation (P < 0.001) and these increases were coupled with increased durations of neuronal inhibition (P < 0.01). The subthalamic nucleus exhibited a higher frequency threshold for stimulation-induced inhibition than the substantia nigra pars reticulata likely due to differing ratios of GABA:glutamate terminals on the soma and/or the nature of their GABAergic inputs (pallidal versus striatal). We suggest that enhancement of inhibitory synaptic plasticity, and frequency-dependent potentiation and depression are putative mechanisms of deep brain stimulation. Furthermore, we foresee that future closed-loop deep brain stimulation systems (with more frequent off stimulation periods) may benefit from inhibitory synaptic potentiation that occurs after high frequency stimulation. PMID:29236966

Long-term reorganization of structural brain networks in a rabbit model of intrauterine growth restriction.

PubMed

Batalle, Dafnis; Muñoz-Moreno, Emma; Arbat-Plana, Ariadna; Illa, Miriam; Figueras, Francesc; Eixarch, Elisenda; Gratacos, Eduard

2014-10-15

Characterization of brain changes produced by intrauterine growth restriction (IUGR) is among the main challenges of modern fetal medicine and pediatrics. This condition affects 5-10% of all pregnancies and is associated with a wide range of neurodevelopmental disorders. Better understanding of the brain reorganization produced by IUGR opens a window of opportunity to find potential imaging biomarkers in order to identify the infants with a high risk of having neurodevelopmental problems and apply therapies to improve their outcomes. Structural brain networks obtained from diffusion magnetic resonance imaging (MRI) is a promising tool to study brain reorganization and to be used as a biomarker of neurodevelopmental alterations. In the present study this technique is applied to a rabbit animal model of IUGR, which presents some advantages including a controlled environment and the possibility to obtain high quality MRI with long acquisition times. Using a Q-Ball diffusion model, and a previously published rabbit brain MRI atlas, structural brain networks of 15 IUGR and 14 control rabbits at 70 days of age (equivalent to pre-adolescence human age) were obtained. The analysis of graph theory features showed a decreased network infrastructure (degree and binary global efficiency) associated with IUGR condition and a set of generalized fractional anisotropy (GFA) weighted measures associated with abnormal neurobehavior. Interestingly, when assessing the brain network organization independently of network infrastructure by means of normalized networks, IUGR showed increased global and local efficiencies. We hypothesize that this effect could reflect a compensatory response to reduced infrastructure in IUGR. These results present new evidence on the long-term persistence of the brain reorganization produced by IUGR that could underlie behavioral and developmental alterations previously described. The described changes in network organization have the potential to be used as biomarkers to monitor brain changes produced by experimental therapies in IUGR animal model. Copyright © 2014 Elsevier Inc. All rights reserved.

Back-Projection Cortical Potential Imaging: Theory and Results.

PubMed

Haor, Dror; Shavit, Reuven; Shapiro, Moshe; Geva, Amir B

2017-07-01

Electroencephalography (EEG) is the single brain monitoring technique that is non-invasive, portable, passive, exhibits high-temporal resolution, and gives a directmeasurement of the scalp electrical potential. Amajor disadvantage of the EEG is its low-spatial resolution, which is the result of the low-conductive skull that "smears" the currents coming from within the brain. Recording brain activity with both high temporal and spatial resolution is crucial for the localization of confined brain activations and the study of brainmechanismfunctionality, whichis then followed by diagnosis of brain-related diseases. In this paper, a new cortical potential imaging (CPI) method is presented. The new method gives an estimation of the electrical activity on the cortex surface and thus removes the "smearing effect" caused by the skull. The scalp potentials are back-projected CPI (BP-CPI) onto the cortex surface by building a well-posed problem to the Laplace equation that is solved by means of the finite elements method on a realistic head model. A unique solution to the CPI problem is obtained by introducing a cortical normal current estimation technique. The technique is based on the same mechanism used in the well-known surface Laplacian calculation, followed by a scalp-cortex back-projection routine. The BP-CPI passed four stages of validation, including validation on spherical and realistic head models, probabilistic analysis (Monte Carlo simulation), and noise sensitivity tests. In addition, the BP-CPI was compared with the minimum norm estimate CPI approach and found superior for multi-source cortical potential distributions with very good estimation results (CC >0.97) on a realistic head model in the regions of interest, for two representative cases. The BP-CPI can be easily incorporated in different monitoring tools and help researchers by maintaining an accurate estimation for the cortical potential of ongoing or event-related potentials in order to have better neurological inferences from the EEG.

Pharmacodynamic and Therapeutic Investigation of Focused Ultrasound-Induced Blood-Brain Barrier Opening for Enhanced Temozolomide Delivery in Glioma Treatment

PubMed Central

Liu, Hao-Li; Huang, Chiung-Yin; Chen, Ju-Yu; Wang, Hay-Yan Jack; Chen, Pin-Yuan; Wei, Kuo-Chen

2014-01-01

Focused ultrasound (FUS) exposure with the presence of microbubbles has been shown to transiently open the blood-brain barrier (BBB), and thus has potential to enhance the delivery of various kinds of therapeutic agents into brain tumors. The purpose of this study was to assess the preclinical therapeutic efficacy of FUS-BBB opening for enhanced temozolomide (TMZ) delivery in glioma treatment. FUS exposure with microbubbles was delivered to open the BBB of nude mice that were either normal or implanted with U87 human glioma cells. Different TMZ dose regimens were tested, ranging from 2.5 to 25 mg/kg. Plasma and brain samples were obtained at different time-points ranging from 0.5 to 4 hours, and the TMZ concentration within samples was quantitated via a developed LC-MS/MS procedure. Tumor progression was followed with T2-MRI, and animal survival and brain tissue histology were conducted. Results demonstrated that FUS-BBB opening caused the local TMZ accumulation in the brain to increase from 6.98 to 19 ng/mg. TMZ degradation time in the tumor core was found to increase from 1.02 to 1.56 hours. Improved tumor progression and animal survival were found at different TMZ doses (up to 15% and 30%, respectively). In conclusion, this study provides preclinical evidence that FUS-BBB opening increases the local concentration of TMZ to improve the control of tumor progression and animal survival, suggesting the potential for clinical application to improve current brain tumor treatment. PMID:25490097

Optically enhanced blood-brain-barrier crossing of plasmonic-active nanoparticles in preclinical brain tumor animal models

NASA Astrophysics Data System (ADS)

Yuan, Hsiangkuo; Wilson, Christy M.; Li, Shuqin; Fales, Andrew M.; Liu, Yang; Grant, Gerald; Vo-Dinh, Tuan

2014-02-01

Nanotechnology provides tremendous biomedical opportunities for cancer diagnosis, imaging, and therapy. In contrast to conventional chemotherapeutic agents where their actual target delivery cannot be easily imaged, integrating imaging and therapeutic properties into one platform facilitates the understanding of pharmacokinetic profiles, and enables monitoring of the therapeutic process in each individual. Such a concept dubbed "theranostics" potentiates translational research and improves precision medicine. One particular challenging application of theranostics involves imaging and controlled delivery of nanoplatforms across blood-brain-barrier (BBB) into brain tissues. Typically, the BBB hinders paracellular flux of drug molecules into brain parenchyma. BBB disrupting agents (e.g. mannitol, focused ultrasound), however, suffer from poor spatial confinement. It has been a challenge to design a nanoplatform not only acts as a contrast agent but also improves the BBB permeation. In this study, we demonstrated the feasibility of plasmonic gold nanoparticles as both high-resolution optical contrast agent and focalized tumor BBB permeation-inducing agent. We specifically examined the microscopic distribution of nanoparticles in tumor brain animal models. We observed that most nanoparticles accumulated at the tumor periphery or perivascular spaces. Nanoparticles were present in both endothelial cells and interstitial matrices. This study also demonstrated a novel photothermal-induced BBB permeation. Fine-tuning the irradiating energy induced gentle disruption of the vascular integrity, causing short-term extravasation of nanomaterials but without hemorrhage. We conclude that our gold nanoparticles are a powerful biocompatible contrast agent capable of inducing focal BBB permeation, and therefore envision a strong potential of plasmonic gold nanoparticle in future brain tumor imaging and therapy.

Magnetic resonance elastography (MRE) of the human brain: technique, findings and clinical applications

NASA Astrophysics Data System (ADS)

Hiscox, Lucy V.; Johnson, Curtis L.; Barnhill, Eric; McGarry, Matt D. J.; Huston 3rd, John; van Beek, Edwin J. R.; Starr, John M.; Roberts, Neil

2016-12-01

Neurological disorders are one of the most important public health concerns in developed countries. Established brain imaging techniques such as magnetic resonance imaging (MRI) and x-ray computerised tomography (CT) have been essential in the identification and diagnosis of a wide range of disorders, although usually are insufficient in sensitivity for detecting subtle pathological alterations to the brain prior to the onset of clinical symptoms—at a time when prognosis for treatment is more favourable. The mechanical properties of biological tissue provide information related to the strength and integrity of the cellular microstructure. In recent years, mechanical properties of the brain have been visualised and measured non-invasively with magnetic resonance elastography (MRE), a particularly sensitive medical imaging technique that may increase the potential for early diagnosis. This review begins with an introduction to the various methods used for the acquisition and analysis of MRE data. A systematic literature search is then conducted to identify studies that have specifically utilised MRE to investigate the human brain. Through the conversion of MRE-derived measurements to shear stiffness (kPa) and, where possible, the loss tangent (rad), a summary of results for global brain tissue and grey and white matter across studies is provided for healthy participants, as potential baseline values to be used in future clinical investigations. In addition, the extent to which MRE has revealed significant alterations to the brain in patients with neurological disorders is assessed and discussed in terms of known pathophysiology. The review concludes by predicting the trends for future MRE research and applications in neuroscience.

Which Donor for Uterus Transplants: Brain-Dead Donor or Living Donor? A Systematic Review.

PubMed

Lavoué, Vincent; Vigneau, Cécile; Duros, Solène; Boudjema, Karim; Levêque, Jean; Piver, Pascal; Aubard, Yves; Gauthier, Tristan

2017-02-01

The aim of this systematic review was to evaluate and compare the pros and cons of using living donors or brain-dead donors in uterus transplantation programs, 2 years after the first worldwide live birth after uterus transplantation. The Medline database and the Central Cochrane Library were used to locate uterine transplantation studies carried out in human or nonhuman primates. All types of articles (case reports, original studies, meta-analyses, reviews) in English or French were considered for inclusion. Overall, 92 articles were screened and 44 were retained for review. Proof of concept for human uterine transplantation was demonstrated in 2014 with a living donor. Compared with a brain-dead donor strategy, a living donor strategy offers greater possibilities for planning surgery and also decreases cold ischemia time, potentially translating into a higher success rate. However, this approach poses ethical problems, given that the donor is exposed to surgery risks but does not derive any direct benefit. A brain-dead donor strategy is more acceptable from an ethical viewpoint, but its feasibility is currently unproven, potentially owing to a lack of compatible donors, and is associated with a longer cold ischemia time and a potentially higher rejection rate. The systematic review demonstrates that uterine transplantation is a major surgical innovation for the treatment of absolute uterine factor infertility. Living and brain-dead donor strategies are not mutually exclusive and, in view of the current scarcity of uterine grafts and the anticipated future rise in demand, both will probably be necessary.

The impact of hyperoxia on brain activity: A resting-state and task-evoked electroencephalography (EEG) study.

PubMed

Sheng, Min; Liu, Peiying; Mao, Deng; Ge, Yulin; Lu, Hanzhang

2017-01-01

A better understanding of the effect of oxygen on brain electrophysiological activity may provide a more mechanistic insight into clinical studies that use oxygen treatment in pathological conditions, as well as in studies that use oxygen to calibrate functional magnetic resonance imaging (fMRI) signals. This study applied electroencephalography (EEG) in healthy subjects and investigated how high a concentration of oxygen in inhaled air (i.e., normobaric hyperoxia) alters brain activity under resting-state and task-evoked conditions. Study 1 investigated its impact on resting EEG and revealed that hyperoxia suppressed α (8-13Hz) and β (14-35Hz) band power (by 15.6±2.3% and 14.1±3.1%, respectively), but did not change the δ (1-3Hz), θ (4-7Hz), and γ (36-75Hz) bands. Sham control experiments did not result in such changes. Study 2 reproduced these findings, and, furthermore, examined the effect of hyperoxia on visual stimulation event-related potentials (ERP). It was found that the main peaks of visual ERP, specifically N1 and P2, were both delayed during hyperoxia compared to normoxia (P = 0.04 and 0.02, respectively). In contrast, the amplitude of the peaks did not show a change. Our results suggest that hyperoxia has a pronounced effect on brain neural activity, for both resting-state and task-evoked potentials.

The impact of hyperoxia on brain activity: A resting-state and task-evoked electroencephalography (EEG) study

PubMed Central

Sheng, Min; Liu, Peiying; Mao, Deng; Ge, Yulin

2017-01-01

A better understanding of the effect of oxygen on brain electrophysiological activity may provide a more mechanistic insight into clinical studies that use oxygen treatment in pathological conditions, as well as in studies that use oxygen to calibrate functional magnetic resonance imaging (fMRI) signals. This study applied electroencephalography (EEG) in healthy subjects and investigated how high a concentration of oxygen in inhaled air (i.e., normobaric hyperoxia) alters brain activity under resting-state and task-evoked conditions. Study 1 investigated its impact on resting EEG and revealed that hyperoxia suppressed α (8-13Hz) and β (14-35Hz) band power (by 15.6±2.3% and 14.1±3.1%, respectively), but did not change the δ (1-3Hz), θ (4-7Hz), and γ (36-75Hz) bands. Sham control experiments did not result in such changes. Study 2 reproduced these findings, and, furthermore, examined the effect of hyperoxia on visual stimulation event-related potentials (ERP). It was found that the main peaks of visual ERP, specifically N1 and P2, were both delayed during hyperoxia compared to normoxia (P = 0.04 and 0.02, respectively). In contrast, the amplitude of the peaks did not show a change. Our results suggest that hyperoxia has a pronounced effect on brain neural activity, for both resting-state and task-evoked potentials. PMID:28464001

[The Dual Nature of the Electrical Signals of the Brain (Electrical and Electrochemical) Which Were Recorded With the Help Polarizable Electrodes From Inert Metals].

PubMed

Dubinin, A G; Reutov, V P; Svinov, M M; Troshin, G I; Shvets-Teneta-Gurii, T B

2015-01-01

In the modern neurophysiology opinion was confirmed that the electrical signals of the brain in the frequency band from DC to electroencephalogram recorded with metallic conductors of inert metal implanted in the brain are formed solely by changes in the electric field of the brain. This paper presents a review of the literature and our own data, according to which the formation of these signals involves two factors. One factor is a change in the charge of the electric double layer electrode having a capacitor property and change the value of its charge with changes in the electric field volume conductor--the brain. Another factor is an electrochemical signal is defined by local changes in the redox potential (E) neuronal-glial populations surrounding the electrode. The paper provides an overviews the electrical and electrochemical properties of the electrodes of the inert metals used in electrophysiology. It is shown that each of these factors has the characteristic parameters over time and amplitude. The data of own studies of local changes in E cortex accompanying brain's response to the implantation of electrodes in the brain's cortex, the natural behavior of animals in the wake-sleep, integrative brain function and effect of pharmacological agents. These results give evidence of the highly informative study of local changes in brain E in order to study energy metabolism in the brain of waking animals, and lay the foundation for the study of local changes in brain energy metabolism in free animal behavior.

SELECTIVE POTENTIATION OF THE METABOTROPIC GLUTAMATE RECEPTOR SUBTYPE 2 BLOCKS PHENCYCLIDINE-INDUCED HYPERLOCOMOTION AND BRAIN ACTIVATION

PubMed Central

HACKLER, E. A.; BYUN, N. E.; JONES, C. K.; WILLIAMS, J. M.; BAHEZA, R.; SENGUPTA, S.; GRIER, M. D.; AVISON, M.; CONN, P. J.; GORE, J. C.

2013-01-01

Previous preclinical and clinical studies have demonstrated the efficacy of group II metabotropic glutamate receptor (mGluR) agonists as potential antipsychotics. Recent studies utilizing mGluR2-, mGluR3-, and double knockout mice support that the antipsychotic effects of those compounds are mediated by mGluR2. Indeed, biphenyl indanone-A (BINA), an allosteric potentiator of mGluR2, is effective in experimental models of psychosis, blocking phencyclidine (PCP)-induced hyperlocomotion and prepulse inhibition deficits in mice. In this study, we administered the NMDA receptor antagonist PCP (5.6 mg/kg i.p.) to rats, an established animal model predictive of schizophrenia. Here, we show that BINA (32 mg/kg i.p.) attenuated PCP-induced locomotor activity in rats. Using behaviorally relevant doses of BINA and PCP, we performed pharmacological magnetic resonance imaging (phMRI) to assess the specific brain regions that underlie the psychotomimetic effects of PCP, and examined how BINA modulated the PCP-induced functional changes in vivo. In anesthetized rats, acute administration of PCP produced robust, sustained blood oxygenation level-dependent (BOLD) activation in specific cortical, limbic, thalamic, and striatal regions. Pretreatment with BINA suppressed the amplitude of the BOLD response to PCP in the prefrontal cortex, caudaute–putamen, nucleus accumbens, and mediodorsal thalamus. Our results show key brain structures underlying PCP-induced behaviors in a preclinical model of schizophrenia, and, importantly, its reversal by potentiation of mGluR2 by BINA, revealing specific brain regions functionally involved in its pharmacological action. Finally, our findings bolster the growing body of evidence that mGluR2 is a viable target for the treatment of schizophrenia. PMID:20350588

Alterations in Error-Related Brain Activity and Post-Error Behavior over Time

ERIC Educational Resources Information Center

Themanson, Jason R.; Rosen, Peter J.; Pontifex, Matthew B.; Hillman, Charles H.; McAuley, Edward

2012-01-01

This study examines the relation between the error-related negativity (ERN) and post-error behavior over time in healthy young adults (N = 61). Event-related brain potentials were collected during two sessions of an identical flanker task. Results indicated changes in ERN and post-error accuracy were related across task sessions, with more…

When Does the Brain Distinguish between Genuine and Ambiguous Smiles? An ERP Study

ERIC Educational Resources Information Center

Calvo, Manuel G.; Marrero, Hipolito; Beltran, David

2013-01-01

Event-related brain potentials (ERPs) were recorded to assess the processing time course of ambiguous facial expressions with a smiling mouth but neutral, fearful, or angry eyes, in comparison with genuinely happy faces (a smile and happy eyes) and non-happy faces (neutral, fearful, or angry mouth and eyes). Participants judged whether the faces…

Brain Dynamics of Word Familiarization in 20-Month-Olds: Effects of Productive Vocabulary Size

ERIC Educational Resources Information Center

Torkildsen, Janne von Koss; Hansen, Hanna Friis; Svangstu, Janne Mari; Smith, Lars; Simonsen, Hanne Gram; Moen, Inger; Lindgren, Magnus

2009-01-01

The present study investigated the brain mechanisms involved during young children's receptive familiarization with new words, and whether the dynamics of these mechanisms are related to the child's productive vocabulary size. To this end, we recorded event-related potentials (ERPs) from 20-month-old children in a pseudoword repetition task.…

THE ADAPTATION FOR GROUP CLASSROOM USE OF CLINICAL TECHNIQUES FOR TEACHING BRAIN-INJURED CHILDREN.

ERIC Educational Resources Information Center

NOVACK, HARRY S.

THIS STUDY SOUGHT TO DEVELOP A PUBLIC SCHOOL PROGRAM FOR BRAIN-INJURED CHILDREN OF AVERAGE OR LOW AVERAGE INTELLECTUAL POTENTIAL. THE OBJECTIVES WERE--(1) TO COLLECT CLINICAL TUTORING TECHNIQUES BEING USED, (2) TO CLASSIFY CLINICAL TUTORIAL METHODS IN A FRAMEWORK USEFUL FOR DEVELOPING TECHNIQUES FOR GROUP TEACHING, (3) TO ADOPT CLINICAL TUTORIAL…

The effects of chronic stress on the human brain: From neurotoxicity, to vulnerability, to opportunity.

PubMed

Lupien, Sonia J; Juster, Robert-Paul; Raymond, Catherine; Marin, Marie-France

2018-04-01

For the last five decades, science has managed to delineate the mechanisms by which stress hormones can impact on the human brain. Receptors for glucocorticoids are found in the hippocampus, amygdala and frontal cortex, three brain regions involved in memory processing and emotional regulation. Studies have shown that chronic exposure to stress is associated with reduced volume of the hippocampus and that chronic stress can modulate volumes of both the amygdala and frontal cortex, suggesting neurotoxic effects of stress hormones on the brain. Yet, other studies report that exposure to early adversity and/or familial/social stressors can increase vulnerability to stress in adulthood. Models have been recently developed to describe the roles that neurotoxic and vulnerability effects can have on the developing brain. These models suggest that developing early stress interventions could potentially counteract the effects of chronic stress on the brain and results going along with this hypothesis are summarized. Copyright © 2018 Elsevier Inc. All rights reserved.

Development of a cerebral circulation model for the automatic control of brain physiology.

PubMed

Utsuki, T

2015-01-01

In various clinical guidelines of brain injury, intracranial pressure (ICP), cerebral blood flow (CBF) and brain temperature (BT) are essential targets for precise management for brain resuscitation. In addition, the integrated automatic control of BT, ICP, and CBF is required for improving therapeutic effects and reducing medical costs and staff burden. Thus, a new model of cerebral circulation was developed in this study for integrative automatic control. With this model, the CBF and cerebral perfusion pressure of a normal adult male were regionally calculated according to cerebrovascular structure, blood viscosity, blood distribution, CBF autoregulation, and ICP. The analysis results were consistent with physiological knowledge already obtained with conventional studies. Therefore, the developed model is potentially available for the integrative control of the physiological state of the brain as a reference model of an automatic control system, or as a controlled object in various control simulations.

Benefits from dietary polyphenols for brain aging and Alzheimer's disease.

PubMed

Rossi, L; Mazzitelli, S; Arciello, M; Capo, C R; Rotilio, G

2008-12-01

Brain aging and the most diffused neurodegenerative diseases of the elderly are characterized by oxidative damage, redox metals homeostasis impairment and inflammation. Food polyphenols can counteract these alterations in vitro and are therefore suggested to have potential anti-aging and brain-protective activities, as also indicated by the results of some epidemiological studies. Despite the huge and increasing amount of the in vitro studies trying to unravel the mechanisms of action of dietary polyphenols, the research in this field is still incomplete, and questions about bioavailability, biotransformation, synergism with other dietary factors, mechanisms of the antioxidant activity, risks inherent to their possible pro-oxidant activities are still unanswered. Most of all, the capacity of the majority of these compounds to cross the blood-brain barrier and reach brain is still unknown. This commentary discusses recent data on these aspects, particularly focusing on effects of curcumin, resveratrol and catechins on Alzheimer's disease.

Brain self-regulation in criminal psychopaths.

PubMed

Konicar, Lilian; Veit, Ralf; Eisenbarth, Hedwig; Barth, Beatrix; Tonin, Paolo; Strehl, Ute; Birbaumer, Niels

2015-03-24

Psychopathic individuals are characterized by impaired affective processing, impulsivity, sensation-seeking, poor planning skills and heightened aggressiveness with poor self-regulation. Based on brain self-regulation studies using neurofeedback of Slow Cortical Potentials (SCPs) in disorders associated with a dysregulation of cortical activity thresholds and evidence of deficient cortical functioning in psychopathy, a neurobiological approach seems to be promising in the treatment of psychopathy. The results of our intensive brain regulation intervention demonstrate, that psychopathic offenders are able to gain control of their brain excitability over fronto-central brain areas. After SCP self-regulation training, we observed reduced aggression, impulsivity and behavioral approach tendencies, as well as improvements in behavioral-inhibition and increased cortical sensitivity for error-processing. This study demonstrates improvements on the neurophysiological, behavioral and subjective level in severe psychopathic offenders after SCP-neurofeedback training and could constitute a novel neurobiologically-based treatment for a seemingly change-resistant group of criminal psychopaths.

Implications of formulation design on lipid-based nanostructured carrier system for drug delivery to brain.

PubMed

Salunkhe, Sachin S; Bhatia, Neela M; Bhatia, Manish S

2016-05-01

The aim of present investigation was to formulate and develop lipid-based nanostructured carriers (NLCs) containing Idebenone (IDE) for delivery to brain. Attempts have been made to evaluate IDE NLCs for its pharmacokinetic and pharmacodynamic profile through the objective of enhancement in bioavailability and effectivity of drug. Nanoprecipitation technique was used for development of drug loaded NLCs. The components solid lipid Precirol ATO 5, oil Miglyol 840, surfactants Tween 80 and Labrasol have been screened out for formulation development by consideration of preformulation parameters including solubility, Required Hydrophilic lipophilic balance (HLB) of lipids and stability study. Developed IDE NLCs were subjected for particle size, zeta potential, entrapment efficiency (%EE), crystallographic investigation, transmission electron microscopy, in vitro drug release, pharmacokinetics, in vivo and stability study. Formulation under investigation has particle size 174.1 ± 2.6 nm, zeta potential -18.65 ± 1.13 mV and% EE 90.68 ± 2.90. Crystallographic studies exemplified for partial amorphization of IDE by molecularly dispersion within lipid crust. IDE NLCs showed drug release 93.56 ± 0.39% at end of 24 h by following Higuchi model which necessitates for appropriate drug delivery with enhancement in bioavailability of drug by 4.6-fold in plasma and 2.8-fold in brain over plain drug loaded aqueous dispersions. In vivo studies revealed that effect of drug was enhanced by prepared lipid nanocarriers. IDE lipid-based nanostructured carriers could have potential for efficient drug delivery to brain with enhancement in bioavailability of drug over the conventional formulations.

Morphological processing in a second language: behavioral and event-related brain potential evidence for storage and decomposition.

PubMed

Hahne, Anja; Mueller, Jutta L; Clahsen, Harald

2006-01-01

This study reports the results of two behavioral and two event-related brain potential experiments examining the processing of inflected words in second-language (L2) learners with Russian as their native language. Two different subsystems of German inflection were studied, participial inflection and noun plurals. For participial forms, L2 learners were found to widely generalize the -t suffixation rule in a nonce-word elicitation task, and in the event-related brain potential experiment, they showed an anterior negativity followed by a P600-both results resembling previous findings from native speakers of German on the same materials. For plural formation, the L2 learners displayed different preference patterns for regular and irregular forms in an off-line plural judgment task. Regular and irregular plural forms also differed clearly with regard to their brain responses. Whereas overapplications of the -s plural rule produced a P600 component, overapplications of irregular patterns elicited an N400. In contrast to native speakers of German, however, the L2 learners did not show an anterior negativity for -s plural overapplications. Taken together, the results show clear dissociations between regular and irregular inflection for both morphological subsystems. We argue that the two processing routes posited by dual-mechanism models of inflection (lexical storage and morphological decomposition) are also employed by L2 learners.

Benomyl induction of brain aromatase and toxic effects in the zebrafish embryo.

PubMed

Kim, Dong-Jae; Seok, Seung-Hyeok; Baek, Min-Won; Lee, Hui-Young; Na, Yi-Rang; Park, Sung-Hoon; Lee, Hyun-Kyoung; Dutta, Noton Kumar; Kawakami, Koichi; Park, Jae-Hak

2009-05-01

Benomyl is a benzimidazole fungicide that has been widely used on a variety of food crops and ornamental plants. It is known to cause adverse effects on reproductive systems, including decreased testicular and epididymal weights and reduced epididymal sperm counts and fertility. The brain aromatase gene is up-regulated by estrogens and estrogen mimics and considered a target gene to screen estrogen mimics. This study was designed to test the estrogenic potential and toxic effects of benomyl in the zebrafish system, and validated this system as a model that may correspond to the effect of benomyl in rodents. Concentrations of 20 x 10(-6), 40 x 10(-6) and 80 x 10(-6) M of benomyl-treated embryos showed decreased survival, hatching and heart rates, and increased incidence of malformations, such as pericardial edema, spinal lordosis, elongated heart, head edema, eye lens protrusion and caudal fin disappearance. Benomyl induced enhanced green fluorescent protein (EGFP) expression in the mediobasal hypothalamus (MBH) in transient zebrafish embryos with a brain aromatase-based reporter gene. In this study, we determined that benomyl has estrogenic potential based on zebrafish brain aromatase gene induction, and that benomyl is toxic at 20 x 10(-6) M concentration and higher. These results demonstrate the usefulness of zebrafish embryos as an in vivo system to examine the estrogenic and developmental toxic potential of unknown compounds.

Addictive drugs and brain stimulation reward.

PubMed

Wise, R A

1996-01-01

Direct electrical or chemical stimulation of specific brain regions can establish response habits similar to those established by natural rewards such as food or sexual contact. Cocaine, mu and delta opiates, nicotine, phencyclidine, and cannabis each have actions that summate with rewarding electrical stimulation of the medial forebrain bundle (MFB). The reward-potentiating effects of amphetamine and opiates are associated with central sites of action where these drugs also have their direct rewarding effects, suggesting common mechanisms for drug reward per se and for drug potentiation of brain stimulation reward. The central sites at which these and perhaps other drugs of abuse potentiate brain stimulation reward and are rewarding in their own right are consistent with the hypothesis that the laboratory reward of brain stimulation and the pharmacological rewards of addictive drugs are habit forming because they act in the brain circuits that subserve more natural and biologically significant rewards.

The influence of victim characteristics on potential jurors' perceptions of brain damage in mild traumatic brain injury.

PubMed

Guilmette, T J; Temple, R O; Kennedy, M L; Weiler, M D; Ruffolo, L F; Dufresne, E

2005-11-01

To determine the influence of victim/plaintiff sex, occupation and intoxication status at the time of injury on potential jurors' judgement about the presence of brain damage in mild traumatic brain injury (MTBI). Survey. One of eight scenarios describing a MTBI from a motor vehicle accident was presented to 460 participants at a Department of Motor Vehicles. Victim sex, occupation (accountant or cafeteria worker) and alcohol intoxication status at the time of injury (sober or intoxicated) were manipulated across eight scenarios. Participants rated whether the victim's complaints at 6 months post-injury were the result of brain damage. Ratings were influenced by victim occupation and intoxication status (chi2>5.3, p<0.03), but not the sex of the victim. The occupational and intoxication status of MTBI victims may influence potential jurors' decision about the presence of brain damage.

Immortalized endothelial cell lines for in vitro blood-brain barrier models: A systematic review.

PubMed

Rahman, Nurul Adhwa; Rasil, Alifah Nur'ain Haji Mat; Meyding-Lamade, Uta; Craemer, Eva Maria; Diah, Suwarni; Tuah, Ani Afiqah; Muharram, Siti Hanna

2016-07-01

Endothelial cells play the most important role in construction of the blood-brain barrier. Many studies have opted to use commercially available, easily transfected or immortalized endothelial cell lines as in vitro blood-brain barrier models. Numerous endothelial cell lines are available, but we do not currently have strong evidence for which cell lines are optimal for establishment of such models. This review aimed to investigate the application of immortalized endothelial cell lines as in vitro blood-brain barrier models. The databases used for this review were PubMed, OVID MEDLINE, ProQuest, ScienceDirect, and SpringerLink. A narrative systematic review was conducted and identified 155 studies. As a result, 36 immortalized endothelial cell lines of human, mouse, rat, porcine and bovine origins were found for the establishment of in vitro blood-brain barrier and brain endothelium models. This review provides a summary of immortalized endothelial cell lines as a guideline for future studies and improvements in the establishment of in vitro blood-brain barrier models. It is important to establish a good and reproducible model that has the potential for multiple applications, in particular a model of such a complex compartment such as the blood-brain barrier. Copyright © 2016 Elsevier B.V. All rights reserved.

Neuroprotective role of Agmatine in Neurological Diseases.

PubMed

Xu, Weilin; Gao, Liansheng; Li, Tao; Shao, Anwen; Zhang, Jianmin

2017-08-08

Neurological diseases have always been one of the leading cause of mobility and mortality world-widely. However, it is still lack of efficient agents. Agmatine, an endogenous polyamine, exerts its diverse biological characteristics and therapeutic potential in varied aspects. Moreover, there has been numerous studies demonstrated the neuroprotective effect of agmatine in varied types of neurological diseases, including acute attack (stroke and trauma brain injury) and chronic neurodegenerative diseases (Parkinson's disease, Alzheimer's disease). The potential mechanism of agmatine -induced neuroprotection includes anti-oxidation, anti-apoptosis, anti-inflammation, brain blood barrier (BBB) protection and brain edema prevention. In this review, we will introduce the neuroprotective effects of agmatine and the underlying mechanisms in the setting of neurological diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Family History of Cancer in Benign Brain Tumor Subtypes Versus Gliomas

PubMed Central

Ostrom, Quinn T.; McCulloh, Christopher; Chen, Yanwen; Devine, Karen; Wolinsky, Yingli; Davitkov, Perica; Robbins, Sarah; Cherukuri, Rajesh; Patel, Ashokkumar; Gupta, Rajnish; Cohen, Mark; Barrios, Jaime Vengoechea; Brewer, Cathy; Schilero, Cathy; Smolenski, Kathy; McGraw, Mary; Denk, Barbara; Naska, Theresa; Laube, Frances; Steele, Ruth; Greene, Dale; Kastl, Alison; Bell, Susan; Aziz, Dina; Chiocca, E. A.; McPherson, Christopher; Warnick, Ronald; Barnett, Gene H.; Sloan, Andrew E.; Barnholtz-Sloan, Jill S.

2012-01-01

Purpose: Family history is associated with gliomas, but this association has not been established for benign brain tumors. Using information from newly diagnosed primary brain tumor patients, we describe patterns of family cancer histories in patients with benign brain tumors and compare those to patients with gliomas. Methods: Newly diagnosed primary brain tumor patients were identified as part of the Ohio Brain Tumor Study. Each patient was asked to participate in a telephone interview about personal medical history, family history of cancer, and other exposures. Information was available from 33 acoustic neuroma (65%), 78 meningioma (65%), 49 pituitary adenoma (73.1%), and 152 glioma patients (58.2%). The association between family history of cancer and each subtype was compared with gliomas using unconditional logistic regression models generating odds ratios (ORs) and 95% confidence intervals. Results: There was no significant difference in family history of cancer between patients with glioma and benign subtypes. Conclusion: The results suggest that benign brain tumor may have an association with family history of cancer. More studies are warranted to disentangle the potential genetic and/or environmental causes for these diseases. PMID:22649779

Longitudinal variations of brain functional connectivity: A case report study based on a mouse model of epilepsy.

PubMed

Erramuzpe, A; Encinas, J M; Sierra, A; Maletic-Savatic, M; Brewster, A L; Anderson, Anne E; Stramaglia, S; Cortes, Jesus M

2015-01-01

Brain Functional Connectivity (FC) quantifies statistical dependencies between areas of the brain. FC has been widely used to address altered function of brain circuits in control conditions compared to different pathological states, including epilepsy, a major neurological disorder. However, FC also has the as yet unexplored potential to help us understand the pathological transformation of the brain circuitry. Our hypothesis is that FC can differentiate global brain interactions across a time-scale of days. To this end, we present a case report study based on a mouse model for epilepsy and analyze longitudinal intracranial electroencephalography data of epilepsy to calculate FC changes from the initial insult (status epilepticus) and over the latent period, when epileptogenic networks emerge, and at chronic epilepsy, when unprovoked seizures occur as spontaneous events. We found that the overall network FC at low frequency bands decreased immediately after status epilepticus was provoked, and increased monotonously later on during the latent period. Overall, our results demonstrate the capacity of FC to address longitudinal variations of brain connectivity across the establishment of pathological states.

Resting State Network Topology of the Ferret Brain

PubMed Central

Zhou, Zhe Charles; Salzwedel, Andrew P.; Radtke-Schuller, Susanne; Li, Yuhui; Sellers, Kristin K.; Gilmore, John H.; Shih, Yen-Yu Ian; Fröhlich, Flavio; Gao, Wei

2016-01-01

Resting state functional magnetic resonance imaging (rsfMRI) has emerged as a versatile tool for non-invasive measurement of functional connectivity patterns in the brain. RsfMRI brain dynamics in rodents, non-human primates, and humans share similar properties; however, little is known about the resting state functional connectivity patterns in the ferret, an animal model with high potential for developmental and cognitive translational study. To address this knowledge-gap, we performed rsfMRI on anesthetized ferrets using a 9.4 tesla MRI scanner, and subsequently performed group-level independent component analysis (gICA) to identify functionally connected brain networks. Group-level ICA analysis revealed distributed sensory, motor, and higher-order networks in the ferret brain. Subsequent connectivity analysis showed interconnected higher-order networks that constituted a putative default mode network (DMN), a network that exhibits altered connectivity in neuropsychiatric disorders. Finally, we assessed ferret brain topological efficiency using graph theory analysis and found that the ferret brain exhibits small-world properties. Overall, these results provide additional evidence for pan-species resting-state networks, further supporting ferret-based studies of sensory and cognitive function. PMID:27596024

Brain activity associated with translation from a visual to a symbolic representation in algebra and geometry.

PubMed

Leikin, Mark; Waisman, Ilana; Shaul, Shelley; Leikin, Roza

2014-03-01

This paper presents a small part of a larger interdisciplinary study that investigates brain activity (using event related potential methodology) of male adolescents when solving mathematical problems of different types. The study design links mathematics education research with neurocognitive studies. In this paper we performed a comparative analysis of brain activity associated with the translation from visual to symbolic representations of mathematical objects in algebra and geometry. Algebraic tasks require translation from graphical to symbolic representation of a function, whereas tasks in geometry require translation from a drawing of a geometric figure to a symbolic representation of its property. The findings demonstrate that electrical activity associated with the performance of geometrical tasks is stronger than that associated with solving algebraic tasks. Additionally, we found different scalp topography of the brain activity associated with algebraic and geometric tasks. Based on these results, we argue that problem solving in algebra and geometry is associated with different patterns of brain activity.

Is there pre-attentive memory-based comparison of pitch?

PubMed

Jacobsen, T; Schröger, E

2001-07-01

The brain's responsiveness to changes in sound frequency has been demonstrated by an overwhelming number of studies. Change detection occurs unintentionally and automatically. It is generally assumed that this brain response, the so-called mismatch negativity (MMN) of the event-related brain potential or evoked magnetic field, is based on the outcome of a memory-comparison mechanism rather than being due to a differential state of refractoriness of tonotopically organized cortical neurons. To the authors' knowledge, however, there is no entirely compelling evidence for this belief. An experimental protocol controlling for refractoriness effects was developed and a true memory-comparison-based brain response to pitch change was demonstrated.

Intranasal insulin as a treatment for Alzheimer's disease: a review of basic research and clinical evidence.

PubMed

Freiherr, Jessica; Hallschmid, Manfred; Frey, William H; Brünner, Yvonne F; Chapman, Colin D; Hölscher, Christian; Craft, Suzanne; De Felice, Fernanda G; Benedict, Christian

2013-07-01

Research in animals and humans has associated Alzheimer's disease (AD) with decreased cerebrospinal fluid levels of insulin in combination with decreased insulin sensitivity (insulin resistance) in the brain. This phenomenon is accompanied by attenuated receptor expression of insulin and insulin-like growth factor, enhanced serine phosphorylation of insulin receptor substrate-1, and impaired transport of insulin across the blood-brain barrier. Moreover, clinical trials have demonstrated that intranasal insulin improves both memory performance and metabolic integrity of the brain in patients suffering from AD or its prodrome, mild cognitive impairment. These results, in conjunction with the finding that insulin mitigates hippocampal synapse vulnerability to beta amyloid, a peptide thought to be causative in the development of AD, provide a strong rationale for hypothesizing that pharmacological strategies bolstering brain insulin signaling, such as intranasal administration of insulin, could have significant potential in the treatment and prevention of AD. With this view in mind, the review at hand will present molecular mechanisms potentially underlying the memory-enhancing and neuroprotective effects of intranasal insulin. Then, we will discuss the results of intranasal insulin studies that have demonstrated that enhancing brain insulin signaling improves memory and learning processes in both cognitively healthy and impaired humans. Finally, we will provide an overview of neuroimaging studies indicating that disturbances in insulin metabolism--such as insulin resistance in obesity, type 2 diabetes and AD--and altered brain responses to insulin are linked to decreased cerebral volume and especially to hippocampal atrophy.

Gelatinized Copper–Capillary Alginate Gel Functions as an Injectable Tissue Scaffolding System for Stem Cell Transplants

PubMed Central

Willenberg, Bradley Jay; Zheng, Tong; Meng, Fan-Wei; Meneses, Juan Carlos; Rossignol, Candace; Batich, Christopher D.; Terada, Naohiro; Steindler, Dennis A.; Weiss, Michael D.

2013-01-01

In severe hypoxic–ischemic brain injury, cellular components such as neurons and astrocytes are injured or destroyed along with the supporting extracellular matrix. This presents a challenge to the field of regenerative medicine since the lack of extracellular matrix and supporting structures makes the transplant milieu inhospitable to the transplanted cells. A potential solution to this problem is the use of a biomaterial to provide the extracellular components needed to keep cells localized in cystic brain regions, allowing the cells to form connections and repair lost brain tissue. Ideally, this biomaterial would be combined with stem cells, which have been proven to have therapeutic potentials, and could be delivered via an injection. To study this approach, we derived a hydrogel biomaterial tissue scaffold from oligomeric gelatin and copper–capillary alginate gel (GCCAG). We then demonstrated that our multipotent astrocytic stem cells (MASCs) could be maintained in GCCAG scaffolds for up to 2 weeks in vitro and that the cells retained their multipotency. We next performed a pilot transplant study in which GCCAG was mixed with MASCs and injected into the brain of a neonatal rat pup. After a week in vivo, our results showed that: the GCCAG biomaterial did not cause a significant reactive gliosis; viable cells were retained within the injected scaffolds; and some delivered cells migrated into the surrounding brain tissue. Therefore, GCCAG tissue scaffolds are a promising, novel injectable system for transplantation of stem cells to the brain. PMID:20699061

Test-retest reliability of functional connectivity networks during naturalistic fMRI paradigms.

PubMed

Wang, Jiahui; Ren, Yudan; Hu, Xintao; Nguyen, Vinh Thai; Guo, Lei; Han, Junwei; Guo, Christine Cong

2017-04-01

Functional connectivity analysis has become a powerful tool for probing the human brain function and its breakdown in neuropsychiatry disorders. So far, most studies adopted resting-state paradigm to examine functional connectivity networks in the brain, thanks to its low demand and high tolerance that are essential for clinical studies. However, the test-retest reliability of resting-state connectivity measures is moderate, potentially due to its low behavioral constraint. On the other hand, naturalistic neuroimaging paradigms, an emerging approach for cognitive neuroscience with high ecological validity, could potentially improve the reliability of functional connectivity measures. To test this hypothesis, we characterized the test-retest reliability of functional connectivity measures during a natural viewing condition, and benchmarked it against resting-state connectivity measures acquired within the same functional magnetic resonance imaging (fMRI) session. We found that the reliability of connectivity and graph theoretical measures of brain networks is significantly improved during natural viewing conditions over resting-state conditions, with an average increase of almost 50% across various connectivity measures. Not only sensory networks for audio-visual processing become more reliable, higher order brain networks, such as default mode and attention networks, but also appear to show higher reliability during natural viewing. Our results support the use of natural viewing paradigms in estimating functional connectivity of brain networks, and have important implications for clinical application of fMRI. Hum Brain Mapp 38:2226-2241, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Endogenous opioidergic dysregulation of pain in fibromyalgia: a PET and fMRI study.

PubMed

Schrepf, Andrew; Harper, Daniel E; Harte, Steven E; Wang, Heng; Ichesco, Eric; Hampson, Johnson P; Zubieta, Jon-Kar; Clauw, Daniel J; Harris, Richard E

2016-10-01

Endogenous opioid system dysfunction potentially contributes to chronic pain in fibromyalgia (FM), but it is unknown if this dysfunction is related to established neurobiological markers of hyperalgesia. We previously reported that µ-opioid receptor (MOR) availability was reduced in patients with FM as compared with healthy controls in several pain-processing brain regions. In the present study, we compared pain-evoked functional magnetic resonance imaging with endogenous MOR binding and clinical pain ratings in female opioid-naive patients with FM (n = 18) using whole-brain analyses and regions of interest from our previous research. Within antinociceptive brain regions, including the dorsolateral prefrontal cortex (r = 0.81, P < 0.001) and multiple regions of the anterior cingulate cortex (all r > 0.67; all P < 0.02), reduced MOR availability was associated with decreased pain-evoked neural activity. Additionally, reduced MOR availability was associated with lower brain activation in the nucleus accumbens (r = 0.47, P = 0.050). In many of these regions, pain-evoked activity and MOR binding potential were also associated with lower clinical affective pain ratings. These findings are the first to link endogenous opioid system tone to regional pain-evoked brain activity in a clinical pain population. Our data suggest that dysregulation of the endogenous opioid system in FM could lead to less excitation in antinociceptive brain regions by incoming noxious stimulation, resulting in the hyperalgesia and allodynia commonly observed in this population. We propose a conceptual model of affective pain dysregulation in FM.

Electrical bioimpedance enabling prompt intervention in traumatic brain injury

NASA Astrophysics Data System (ADS)

Seoane, Fernando; Atefi, S. Reza

2017-05-01

Electrical Bioimpedance (EBI) is a well spread technology used in clinical practice across the world. Advancements in Textile material technology with conductive textile fabrics and textile-electronics integration have allowed exploring potential applications for Wearable Measurement Sensors and Systems exploiting. The sensing principle of electrical bioimpedance is based on the intrinsic passive dielectric properties of biological tissue. Using a pair of electrodes, tissue is electrically stimulated and the electrical response can be sensed with another pair of surface electrodes. EBI spectroscopy application for cerebral monitoring of neurological conditions such as stroke and perinatal asphyxia in newborns have been justified using animal studies and computational simulations. Such studies have shown proof of principle that neurological pathologies indeed modify the dielectric composition of the brain that is detectable via EBI. Similar to stroke, Traumatic Brain Injury (TBI) also affects the dielectric properties of brain tissue that can be detected via EBI measurements. Considering the portable and noninvasive characteristics of EBI it is potentially useful for prehospital triage of TBI patients where. In the battlefield blast induced Traumatic Brain Injuries are very common. Brain damage must be assessed promptly to have a chance to prevent severe damage or eventually death. The relatively low-complexity of the sensing hardware required for EBI sensing and the already proven compatibility with textile electrodes suggest the EBI technology is indeed a candidate for developing a handheld device equipped with a sensorized textile cap to produce an examination in minutes for enabling medically-guided prompt intervention.

Searching for the philosopher's stone: promising links between meditation and brain preservation.

PubMed

Luders, Eileen; Cherbuin, Nicolas

2016-06-01

In the context of an aging population and increased prevalence of dementia and other neurodegenerative diseases, developing strategies to decrease the negative effects of aging is imperative. The scientific study of meditation as a potential tool to downregulate processes implicated in brain aging is an emerging field, and a growing body of research suggests that mindfulness practices are beneficial for cerebral resilience. Adding further evidence to this notion, an increasing number of imaging studies report effects of meditation on brain structure that are consistent with our understanding of neuroprotection. Here, we review the published findings in this field of research addressing the question of whether meditation diminishes age-related brain degeneration. Altogether, although analyses are still sparse and based on cross-sectional data, study outcomes suggest that meditation might be beneficial for brain preservation-both with respect to gray and white matter-possibly by slowing down the natural (age-related) decrease of brain tissue. Nevertheless, it should also be recognized that, until robust longitudinal data become available, there is no evidence for causation between meditation and brain preservation. This review includes a comprehensive commentary on limitations of the existing research and concludes with implications and directions for future studies. © 2016 New York Academy of Sciences.

A step into the anarchist’s mind: examining political attitudes and ideology through event-related brain potentials

PubMed Central

Van Hiel, Alain; Pattyn, Sven; Onraet, Emma; Severens, Els

2012-01-01

The present study investigates patterns of event-related brain potentials following the presentation of attitudinal stimuli among political moderates (N = 12) and anarchists (N = 11). We used a modified oddball paradigm to investigate the evaluative inconsistency effect elicited by stimuli embedded in a sequence of contextual stimuli with an opposite valence. Increased late positive potentials (LPPs) of extreme political attitudes were observed. Moreover, this LPP enhancement was larger among anarchists than among moderates, indicating that an extreme political attitude of a moderate differs from an extreme political attitude of an anarchist. The discussion elaborates on the meaning of attitude extremity for moderates and extremists. PMID:21421734

The effects of laboratory housing and spatial enrichment on brain size and metabolic rate in the eastern mosquitofish, Gambusia holbrooki

PubMed Central

Turschwell, Mischa P.; White, Craig R.

2016-01-01

ABSTRACT It has long been hypothesised that there is a functional correlation between brain size and metabolic rate in vertebrates. The present study tested this hypothesis in wild-caught adult mosquitofish Gambusia holbrooki by testing for an intra-specific association between resting metabolic rate (RMR) and brain size while controlling for variation in body size, and through the examination of the effects of spatial enrichment and laboratory housing on body mass-independent measures of brain size and RMR. Controlling for body mass, there was no relationship between brain size and RMR in wild-caught fish. Contrary to predictions, spatial enrichment caused a decrease in mass-independent brain size, highlighting phenotypic plasticity in the adult brain. As expected, after controlling for differences in body size, wild-caught fish had relatively larger brains than fish that had been maintained in the laboratory for a minimum of six weeks, but wild-caught fish also had significantly lower mass-independent RMR. This study demonstrates that an organisms' housing environment can cause significant plastic changes to fitness related traits including brain size and RMR. We therefore conclude that current standard laboratory housing conditions may cause captive animals to be non-representative of their wild counterparts, potentially undermining the transferability of previous laboratory-based studies of aquatic ectothermic vertebrates to wild populations. PMID:26794608

Using cholinergic M1 receptor positive allosteric modulators to improve memory via enhancement of brain cholinergic communication.

PubMed

Chambon, Caroline; Jatzke, Claudia; Wegener, Nico; Gravius, Andreas; Danysz, Wojciech

2012-12-15

Benzylquinolone carboxylic acid (BQCA) is a recently described cholinergic muscarinic M(1) receptor positive allosteric modulator having potential as cognitive enhancer in dementia. The present study focused on the characterisation of BQCA's mode of action in relation to positive effects on memory and side-effects in an animal model. To get insight into this mode of action, in vitro receptor potency/left shift experiments in cells stably expressing the rat's M(1) receptor were performed. They revealed an inflection point value of BQCA corresponding to 306nM, and potentiation of the agonist response up to 47-fold in presence of 10μM of BQCA. In vivo, brain microdialysis showed a maximal brain level of 270nM, 40min after i.p. administration at 10mg/kg. Based on in vitro data obtained with this dose, it can be concluded that BQCA reaches brain levels which should potentiate the agonist response about 4-fold. Behavioural data confirmed that BQCA used at 10mg/kg attenuated scopolamine-induced memory deficit in a spontaneous alternation task. Moreover, BQCA showed no side effect at 10mg/kg and above in spontaneous locomotion and salivation tests. The profile of BQCA observed in the present study displays a clear advantage over the M(1)-M(3) agonist cevimeline. The present data show the therapeutic potential of the M(1) receptor positive allosteric modulator BQCA for the treatment of memory deficits observed in Alzheimer's disease. Copyright © 2012. Published by Elsevier B.V.

Task-based neurofeedback training: A novel approach toward training executive functions.

PubMed

Hosseini, S M Hadi; Pritchard-Berman, Mika; Sosa, Natasha; Ceja, Angelica; Kesler, Shelli R

2016-07-01

Cognitive training is an emergent approach to improve cognitive functions in various neurodevelopmental and neurodegenerative diseases. However, current training programs can be relatively lengthy, making adherence potentially difficult for patients with cognitive difficulties. Previous studies suggest that providing individuals with real-time feedback about the level of brain activity (neurofeedback) can potentially help them learn to control the activation of specific brain regions. In the present study, we developed a novel task-based neurofeedback training paradigm that benefits from the effects of neurofeedback in parallel with computerized training. We focused on executive function training given its core involvement in various developmental and neurodegenerative diseases. Near-infrared spectroscopy (NIRS) was employed for providing neurofeedback by measuring changes in oxygenated hemoglobin in the prefrontal cortex. Of the twenty healthy adult participants, ten received real neurofeedback (NFB) on prefrontal activity during cognitive training, and ten were presented with sham feedback (SHAM). Compared with SHAM, the NFB group showed significantly improved executive function performance including measures of working memory after four sessions of training (100min total). The NFB group also showed significantly reduced training-related brain activity in the executive function network including right middle frontal and inferior frontal regions compared with SHAM. Our data suggest that providing neurofeedback along with cognitive training can enhance executive function after a relatively short period of training. Similar designs could potentially be used for patient populations with known neuropathology, potentially helping them to boost/recover the activity in the affected brain regions. Copyright © 2016 Elsevier Inc. All rights reserved.

Plasticity during Early Brain Development Is Determined by Ontogenetic Potential.

PubMed

Krägeloh-Mann, Ingeborg; Lidzba, Karen; Pavlova, Marina A; Wilke, Marko; Staudt, Martin

2017-04-01

Two competing hypotheses address neuroplasticity during early brain development: the "Kennard principle" describes the compensatory capacities of the immature developing CNS as superior to those of the adult brain, whereas the "Hebb principle" argues that the young brain is especially sensitive to insults. We provide evidence that these principles are not mutually exclusive. Following early brain lesions that are unilateral, the brain can refer to homotopic areas of the healthy hemisphere. This potential for reorganization is unique to the young brain but available only when, during ontogenesis of brain development, these areas have been used for the functions addressed. With respect to motor function, ipsilateral motor tracts can be recruited, which are only available during early brain development. Language can be reorganized to the right after early left hemispheric lesions, as the representation of the language network is initially bilateral. However, even in these situations, compensatory capacities of the developing brain are found to have limitations, probably defined by early determinants. Thus, plasticity and adaptivity are seen only within ontogenetic potential; that is, axonal or cortical structures cannot be recruited beyond early developmental possibilities. The young brain is probably more sensitive and vulnerable to lesions when these are bilateral. This is shown here for bilateral periventricular white matter lesions that clearly have an impact on cortical architecture and function, thus probably interfering with early network building. Georg Thieme Verlag KG Stuttgart · New York.

Housekeeping while brain's storming Validation of normalizing factors for gene expression studies in a murine model of traumatic brain injury

PubMed Central

Rhinn, Hervé; Marchand-Leroux, Catherine; Croci, Nicole; Plotkine, Michel; Scherman, Daniel; Escriou, Virginie

2008-01-01

Background Traumatic brain injury models are widely studied, especially through gene expression, either to further understand implied biological mechanisms or to assess the efficiency of potential therapies. A large number of biological pathways are affected in brain trauma models, whose elucidation might greatly benefit from transcriptomic studies. However the suitability of reference genes needed for quantitative RT-PCR experiments is missing for these models. Results We have compared five potential reference genes as well as total cDNA level monitored using Oligreen reagent in order to determine the best normalizing factors for quantitative RT-PCR expression studies in the early phase (0–48 h post-trauma (PT)) of a murine model of diffuse brain injury. The levels of 18S rRNA, and of transcripts of β-actin, glyceraldehyde-3P-dehydrogenase (GAPDH), β-microtubulin and S100β were determined in the injured brain region of traumatized mice sacrificed at 30 min, 3 h, 6 h, 12 h, 24 h and 48 h post-trauma. The stability of the reference genes candidates and of total cDNA was evaluated by three different methods, leading to the following rankings as normalization factors, from the most suitable to the less: by using geNorm VBA applet, we obtained the following sequence: cDNA(Oligreen); GAPDH > 18S rRNA > S100β > β-microtubulin > β-actin; by using NormFinder Excel Spreadsheet, we obtained the following sequence: GAPDH > cDNA(Oligreen) > S100β > 18S rRNA > β-actin > β-microtubulin; by using a Confidence-Interval calculation, we obtained the following sequence: cDNA(Oligreen) > 18S rRNA; GAPDH > S100β > β-microtubulin > β-actin. Conclusion This work suggests that Oligreen cDNA measurements, 18S rRNA and GAPDH or a combination of them may be used to efficiently normalize qRT-PCR gene expression in mouse brain trauma injury, and that β-actin and β-microtubulin should be avoided. The potential of total cDNA as measured by Oligreen as a first-intention normalizing factor with a broad field of applications is highlighted. Pros and cons of the three methods of normalization factors selection are discussed. A generic time- and cost-effective procedure for normalization factor validation is proposed. PMID:18611280

Fetal magnetic resonance imaging (MRI): a tool for a better understanding of normal and abnormal brain development.

PubMed

Saleem, Sahar N

2013-07-01

Knowledge of the anatomy of the developing fetal brain is essential to detect abnormalities and understand their pathogenesis. Capability of magnetic resonance imaging (MRI) to visualize the brain in utero and to differentiate between its various tissues makes fetal MRI a potential diagnostic and research tool for the developing brain. This article provides an approach to understand the normal and abnormal brain development through schematic interpretation of fetal brain MR images. MRI is a potential screening tool in the second trimester of pregnancies in fetuses at risk for brain anomalies and helps in describing new brain syndromes with in utero presentation. Accurate interpretation of fetal MRI can provide valuable information that helps genetic counseling, facilitates management decisions, and guides therapy. Fetal MRI can help in better understanding the pathogenesis of fetal brain malformations and can support research that could lead to disease-specific interventions.

Induction of brain tumor stem cell apoptosis by FTY720: a potential therapeutic agent for glioblastoma.

PubMed

Estrada-Bernal, Adriana; Palanichamy, Kamalakannan; Ray Chaudhury, Abhik; Van Brocklyn, James R

2012-04-01

FTY720 is a sphingosine analogue that down regulates expression of sphingosine-1-phosphate receptors and causes apoptosis of multiple tumor cell types, including glioma cells. This study examined the effect of FTY720 on brain tumor stem cells (BTSCs) derived from human glioblastoma (GBM) tissue. FTY720 treatment of BTSCs led to rapid inactivation of ERK MAP kinase, leading to upregulation of the BH3-only protein Bim and apoptosis. In combination with temozolomide (TMZ), the current standard chemotherapeutic agent for GBM, FTY720 synergistically induced BTSC apoptosis. FTY720 also slowed growth of intracranial xenograft tumors in nude mice and augmented the therapeutic effect of TMZ, leading to enhanced survival. Furthermore, the combination of FTY720 and TMZ decreased the invasiveness of BTSCs in mouse brains. FTY720 is known to cross the blood-brain barrier and recently received Food and Drug Administration approval for treatment of relapsing multiple sclerosis. Thus, FTY720 is an excellent potential therapeutic agent for treatment of GBM.

Mild hypothermia as a treatment for central nervous system injuries: Positive or negative effects

PubMed Central

Darwazeh, Rami; Yan, Yi

2013-01-01

Besides local neuronal damage caused by the primary insult, central nervous system injuries may secondarily cause a progressive cascade of related events including brain edema, ischemia, oxida-tive stress, excitotoxicity, and dysregulation of calcium homeostasis. Hypothermia is a beneficial strategy in a variety of acute central nervous system injuries. Mild hypothermia can treat high intra-cranial pressure following traumatic brain injuries in adults. It is a new treatment that increases sur-vival and quality of life for patients suffering from ischemic insults such as cardiac arrest, stroke, and neurogenic fever following brain trauma. Therapeutic hypothermia decreases free radical produc-tion, inflammation, excitotoxicity and intracranial pressure, and improves cerebral metabolism after traumatic brain injury and cerebral ischemia, thus protecting against central nervous system dam-age. Although a series of pathological and physiological changes as well as potential side effects are observed during hypothermia treatment, it remains a potential therapeutic strategy for central nervous system injuries and deserves further study. PMID:25206579

Mild hypothermia as a treatment for central nervous system injuries: Positive or negative effects.

PubMed

Darwazeh, Rami; Yan, Yi

2013-10-05

Besides local neuronal damage caused by the primary insult, central nervous system injuries may secondarily cause a progressive cascade of related events including brain edema, ischemia, oxida-tive stress, excitotoxicity, and dysregulation of calcium homeostasis. Hypothermia is a beneficial strategy in a variety of acute central nervous system injuries. Mild hypothermia can treat high intra-cranial pressure following traumatic brain injuries in adults. It is a new treatment that increases sur-vival and quality of life for patients suffering from ischemic insults such as cardiac arrest, stroke, and neurogenic fever following brain trauma. Therapeutic hypothermia decreases free radical produc-tion, inflammation, excitotoxicity and intracranial pressure, and improves cerebral metabolism after traumatic brain injury and cerebral ischemia, thus protecting against central nervous system dam-age. Although a series of pathological and physiological changes as well as potential side effects are observed during hypothermia treatment, it remains a potential therapeutic strategy for central nervous system injuries and deserves further study.

An 'integrative neuroscience' perspective on ADHD: linking cognition, emotion, brain and genetic measures with implications for clinical support.

PubMed

Williams, Leanne M; Tsang, Tracey W; Clarke, Simon; Kohn, Michael

2010-10-01

There remains a translational gap between research findings and their implementation in clinical practice that applies to attention-deficit/hyperactivity disorder (ADHD), as well as to other major disorders of brain health in childhood, adolescence and adulthood. Research studies have identified potential 'markers' to support diagnostic, functional assessment and treatment decisions, but there is little consensus about these markers. Of these potential markers, cognitive measures of thinking functions, such as sustaining attention and associated electrical brain activity, show promise in complementing the clinical management process. Emerging evidence highlights the relevance of emotional, as well as thinking, functions to ADHD. Here, we outline an integrative neuroscience framework for ADHD that offers one means to bring together cognitive measures of thinking functions with measures of emotion, and their brain and genetic correlates. Understanding these measures and the relationships between them is a first step towards the development of tools that will help to assess the heterogeneity of ADHD, and aid in tailoring treatment choices.

Synthetic tactile perception induced by transcranial alternating-current stimulation can substitute for natural sensory stimulus in behaving rabbits.

PubMed

Márquez-Ruiz, Javier; Ammann, Claudia; Leal-Campanario, Rocío; Ruffini, Giulio; Gruart, Agnès; Delgado-García, José M

2016-01-21

The use of brain-derived signals for controlling external devices has long attracted the attention from neuroscientists and engineers during last decades. Although much effort has been dedicated to establishing effective brain-to-computer communication, computer-to-brain communication feedback for "closing the loop" is now becoming a major research theme. While intracortical microstimulation of the sensory cortex has already been successfully used for this purpose, its future application in humans partly relies on the use of non-invasive brain stimulation technologies. In the present study, we explore the potential use of transcranial alternating-current stimulation (tACS) for synthetic tactile perception in alert behaving animals. More specifically, we determined the effects of tACS on sensory local field potentials (LFPs) and motor output and tested its capability for inducing tactile perception using classical eyeblink conditioning in the behaving animal. We demonstrated that tACS of the primary somatosensory cortex vibrissa area could indeed substitute natural stimuli during training in the associative learning paradigm.

Importance of Multimodal MRI in Characterizing Brain Tissue and Its Potential Application for Individual Age Prediction.

PubMed

Cherubini, Andrea; Caligiuri, Maria Eugenia; Peran, Patrice; Sabatini, Umberto; Cosentino, Carlo; Amato, Francesco

2016-09-01

This study presents a voxel-based multiple regression analysis of different magnetic resonance image modalities, including anatomical T1-weighted, T2(*) relaxometry, and diffusion tensor imaging. Quantitative parameters sensitive to complementary brain tissue alterations, including morphometric atrophy, mineralization, microstructural damage, and anisotropy loss, were compared in a linear physiological aging model in 140 healthy subjects (range 20-74 years). The performance of different predictors and the identification of the best biomarker of age-induced structural variation were compared without a priori anatomical knowledge. The best quantitative predictors in several brain regions were iron deposition and microstructural damage, rather than macroscopic tissue atrophy. Age variations were best resolved with a combination of markers, suggesting that multiple predictors better capture age-induced tissue alterations. The results of the linear model were used to predict apparent age in different regions of individual brain. This approach pointed to a number of novel applications that could potentially help highlighting areas particularly vulnerable to disease.

Precise and accurate assay of pregnenolone and five other neurosteroids in monkey brain tissue by LC-MS/MS.

PubMed

Dury, Alain Y; Ke, Yuyong; Labrie, Fernand

2016-09-01

A series of steroids present in the brain have been named "neurosteroids" following the possibility of their role in the central nervous system impairments such as anxiety disorders, depression, premenstrual dysphoric disorder (PMDD), addiction, or even neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Study of their potential role requires a sensitive and accurate assay of their concentration in the monkey brain, the closest model to the human. We have thus developed a robust, precise and accurate liquid chromatography-tandem mass spectrometry method for the assay of pregnenolone, pregnanolone, epipregnanolone, allopregnanolone, epiallopregnanolone, and androsterone in the cynomolgus monkey brain. The extraction method includes a thorough sample cleanup using protein precipitation and phospholipid removal, followed by hexane liquid-liquid extraction and a Girard T ketone-specific derivatization. This method opens the possibility of investigating the potential implication of these six steroids in the most suitable animal model for neurosteroid-related research. Copyright © 2016 Elsevier Inc. All rights reserved.

Methodological dimensions of transcranial brain stimulation with the electrical current in human.

PubMed

Rostami, Maryam; Golesorkhi, Mehrshad; Ekhtiari, Hamed

2013-01-01

Transcranial current stimulation (TCS) is a neuromodulation method in which the patient is exposed to a mild electric current (direct or alternating) at 1-2 mA, resulting in an increase or a decrease in the brain excitability. This modification in neural activities can be used as a method for functional human brain mapping with causal inferences. This method might also facilitate the treatments of many neuropsychiatric disorders based on its inexpensive, simple, safe, noninvasive, painless, semi-focal excitatory and inhibitory effects. Given this, a comparison amongst different brain stimulation modalities has been made to determine the potential advantages of the TCS method. In addition, considerable methodological details on using TCS in basic and clinical neuroscience studies in human subjects have been introduced. Technical characteristics of TCS devices and their related accessories with regard to safety concerns have also been well articulated. Finally, some TCS application opportunities have been emphasized, including its potential use in the near future.

Copine1 regulates neural stem cell functions during brain development.

PubMed

Kim, Tae Hwan; Sung, Soo-Eun; Cheal Yoo, Jae; Park, Jae-Yong; Yi, Gwan-Su; Heo, Jun Young; Lee, Jae-Ran; Kim, Nam-Soon; Lee, Da Yong

2018-01-01

Copine 1 (CPNE1) is a well-known phospholipid binding protein in plasma membrane of various cell types. In brain cells, CPNE1 is closely associated with AKT signaling pathway, which is important for neural stem cell (NSC) functions during brain development. Here, we investigated the role of CPNE1 in the regulation of brain NSC functions during brain development and determined its underlying mechanism. In this study, abundant expression of CPNE1 was observed in neural lineage cells including NSCs and immature neurons in human. With mouse brain tissues in various developmental stages, we found that CPNE1 expression was higher at early embryonic stages compared to postnatal and adult stages. To model developing brain in vitro, we used primary NSCs derived from mouse embryonic hippocampus. Our in vitro study shows decreased proliferation and multi-lineage differentiation potential in CPNE1 deficient NSCs. Finally, we found that the deficiency of CPNE1 downregulated mTOR signaling in embryonic NSCs. These data demonstrate that CPNE1 plays a key role in the regulation of NSC functions through the activation of AKT-mTOR signaling pathway during brain development. Copyright © 2017 Elsevier Inc. All rights reserved.

Carbohydrates as a cerebral metabolic fuel.

PubMed

Evans, M; Amiel, S A

1998-03-01

The human brain is an extremely active metabolic organ with little endogenous stores of energy. It is thus dependent on circulating glucose to fuel metabolism and support cognitive functioning. However there is growing evidence that the human brain is able to utilise other non-glucose fuels during times of glucose lack. We review the evidence for the potential of the human brain to use the alternate fuels lactate and beta-hydroxybutyrate, and some recent studies examining the ability of regions of brain to use non-glucose lipid fuels. The human brain does not seem to have the ability to use the gluconeogenic precursor alanine to any significant degree. Regionality within the brain can be examined in vivo by the use of positron emission tomography, which offers the exciting prospect of studying human brain metabolism in vivo using a simple and non-interventional technique. Increased understanding of the brain's metabolism, the way in which hypoglycaemia is recognised and the manner in which this can be altered in the syndrome of hypoglycaemia unawareness and deficient counterregulation will help develop further strategies to prevent the clinical problems associated with hypoglycaemia in insulin-dependent diabetic adults and children.

Functional MR imaging assessment of a non-responsive brain injured patient.

PubMed

Moritz, C H; Rowley, H A; Haughton, V M; Swartz, K R; Jones, J; Badie, B

2001-10-01

Functional magnetic resonance imaging (fMRI) was requested to assist in the evaluation of a comatose 38-year-old woman who had sustained multiple cerebral contusions from a motor vehicle accident. Previous electrophysiologic studies suggested absence of thalamocortical processing in response to median nerve stimulation. Whole-brain fMRI was performed utilizing visual, somatosensory, and auditory stimulation paradigms. Results demonstrated intact task-correlated sensory and cognitive blood oxygen level dependent (BOLD) hemodynamic response to stimuli. Electrodiagnostic studies were repeated and evoked potentials indicated supratentorial recovery in the cerebrum. At 3-months post trauma the patient had recovered many cognitive & sensorimotor functions, accurately reflecting the prognostic fMRI evaluation. These results indicate that fMRI examinations may provide a useful evaluation for brain function in non-responsive brain trauma patients.

Nootropic potential of Ashwagandha leaves: Beyond traditional root extracts.

PubMed

Wadhwa, Renu; Konar, Arpita; Kaul, Sunil C

2016-05-01

Rapidly increasing aging population and environmental stressors are the two main global concerns of the modern society. These have brought in light rapidly increasing incidence of a variety of pathological conditions including brain tumors, neurodegenerative & neuropsychiatric disorders, and new challenges for their treatment. The overlapping symptoms, complex etiology and lack of full understanding of the brain structure and function to-date further complicate these tasks. On the other hand, several herbal reagents with a long history of their use have been asserted to possess neurodifferentiation, neuroregenerative and neuroprotective potentials, and hence been recommended as supplement to enhance and maintain brain health and function. Although they have been claimed to function by holistic approach resulting in maintaining body homeostasis and brain health, there are not enough laboratory studies in support to these and mechanism(s) of such beneficial activities remain largely undefined. One such herb is Ashwagandha, also called "Queen of Ayurveda" for its popular use in Indian traditional home medicine because of its extensive benefits including anticancer, anti-stress and remedial potential for aging and neurodegenerative pathologies. However, active principles and underlying mechanism(s) of action remain largely unknown. Here we provide a review on the effects of Ashwagandha extracts and active principles, and underlying molecular mechanism(s) for brain pathologies. We highlight our findings on the nootropic potential of Ashwagandha leaves. The effects of Ashwagandha leaf extracts are multidimensional ranging from differentiation of neuroblastoma and glioma cells, reversal of Alzheimer and Parkinson's pathologies, protection against environmental neurotoxins and enhancement of memory. Copyright © 2015 Elsevier Ltd. All rights reserved.

Monoamine oxidase B is elevated in Alzheimer disease neurons, is associated with γ-secretase and regulates neuronal amyloid β-peptide levels.

PubMed

Schedin-Weiss, Sophia; Inoue, Mitsuhiro; Hromadkova, Lenka; Teranishi, Yasuhiro; Yamamoto, Natsuko Goto; Wiehager, Birgitta; Bogdanovic, Nenad; Winblad, Bengt; Sandebring-Matton, Anna; Frykman, Susanne; Tjernberg, Lars O

2017-08-01

Increased levels of the pathogenic amyloid β-peptide (Aβ), released from its precursor by the transmembrane protease γ-secretase, are found in Alzheimer disease (AD) brains. Interestingly, monoamine oxidase B (MAO-B) activity is also increased in AD brain, but its role in AD pathogenesis is not known. Recent neuroimaging studies have shown that the increased MAO-B expression in AD brain starts several years before the onset of the disease. Here, we show a potential connection between MAO-B, γ-secretase and Aβ in neurons. MAO-B immunohistochemistry was performed on postmortem human brain. Affinity purification of γ-secretase followed by mass spectrometry was used for unbiased identification of γ-secretase-associated proteins. The association of MAO-B with γ-secretase was studied by coimmunoprecipitation from brain homogenate, and by in-situ proximity ligation assay (PLA) in neurons as well as mouse and human brain sections. The effect of MAO-B on Aβ production and Notch processing in cell cultures was analyzed by siRNA silencing or overexpression experiments followed by ELISA, western blot or FRET analysis. Methodology for measuring relative intraneuronal MAO-B and Aβ42 levels in single cells was developed by combining immunocytochemistry and confocal microscopy with quantitative image analysis. Immunohistochemistry revealed MAO-B staining in neurons in the frontal cortex, hippocampus CA1 and entorhinal cortex in postmortem human brain. Interestingly, the neuronal staining intensity was higher in AD brain than in control brain in these regions. Mass spectrometric data from affinity purified γ-secretase suggested that MAO-B is a γ-secretase-associated protein, which was confirmed by immunoprecipitation and PLA, and a neuronal location of the interaction was shown. Strikingly, intraneuronal Aβ42 levels correlated with MAO-B levels, and siRNA silencing of MAO-B resulted in significantly reduced levels of intraneuronal Aβ42. Furthermore, overexpression of MAO-B enhanced Aβ production. This study shows that MAO-B levels are increased not only in astrocytes but also in pyramidal neurons in AD brain. The study also suggests that MAO-B regulates Aβ production in neurons via γ-secretase and thereby provides a key to understanding the relationship between MAO-B and AD pathogenesis. Potentially, the γ-secretase/MAO-B association may be a target for reducing Aβ levels using protein-protein interaction breakers.

[Effect of a new derivative of glutamic and apovincaminic acids on brain metabolism in post-ischemic period].

PubMed

Makarova, L M; Prikhod'ko, M A; Pogorelyĭ, V E; Skachilova, S Ia; Mirzoian, R S

2014-01-01

Neuroprotective properties of the new derivative of glutamic and apovincaminic acids, ethyl -(3-alpha,16-alpha)-eburnamenin-14-carbopxylate of 2-aminopentadionic acid (LHT 1-02) were studied on a model of acute brain ischemia in cats. LHT 1-02 has proved to be more effective than the reference drugs vinpocetin and glycine in preventing the reperfusive damage, which was manifested by decreased postischemic hyperglycemia, activated utilization of oxygen in the brain, and suppressed postischemic metabolic lactate acidosis. Thus, the results of this comparative study show expediency of further investigations of LHT 1 - 02 as a potential neuroprotective drug.

Declarative and nondeclarative memory: multiple brain systems supporting learning and memory.

PubMed

Squire, L R

1992-01-01

Abstract The topic of multiple forms of memory is considered from a biological point of view. Fact-and-event (declarative, explicit) memory is contrasted with a collection of non conscious (non-declarative, implicit) memory abilities including skills and habits, priming, and simple conditioning. Recent evidence is reviewed indicating that declarative and non declarative forms of memory have different operating characteristics and depend on separate brain systems. A brain-systems framework for understanding memory phenomena is developed in light of lesion studies involving rats, monkeys, and humans, as well as recent studies with normal humans using the divided visual field technique, event-related potentials, and positron emission tomography (PET).

Global loss of acetylcholinesterase activity with mitochondrial complexes inhibition and inflammation in brain of hypercholesterolemic mice.

PubMed

Paul, Rajib; Borah, Anupom

2017-12-20

There exists an intricate relationship between hypercholesterolemia (elevated plasma cholesterol) and brain functions. The present study aims to understand the impact of hypercholesterolemia on pathological consequences in mouse brain. A chronic mouse model of hypercholesterolemia was induced by giving high-cholesterol diet for 12 weeks. The hypercholesterolemic mice developed cognitive impairment as evident from object recognition memory test. Cholesterol accumulation was observed in four discrete brain regions, such as cortex, striatum, hippocampus and substantia nigra along with significantly damaged blood-brain barrier by hypercholesterolemia. The crucial finding is the loss of acetylcholinesterase activity with mitochondrial dysfunction globally in the brain of hypercholesterolemic mice, which is related to the levels of cholesterol. Moreover, the levels of hydroxyl radical were elevated in the regions of brain where the activity of mitochondrial complexes was found to be reduced. Intriguingly, elevations of inflammatory stress markers in the cholesterol-rich brain regions were observed. As cognitive impairment, diminished brain acetylcholinesterase activity, mitochondrial dysfunctions, and inflammation are the prima facie pathologies of neurodegenerative diseases, the findings impose hypercholesterolemia as potential risk factor towards brain dysfunction.

NMR-based metabolomics approach to study the toxicity of lambda-cyhalothrin to goldfish (Carassius auratus).

PubMed

Li, Minghui; Wang, Junsong; Lu, Zhaoguang; Wei, Dandan; Yang, Minghua; Kong, Lingyi

2014-01-01

In this study, a (1)H nuclear magnetic resonance (NMR) based metabolomics approach was applied to investigate the toxicity of lambda-cyhalothrin (LCT) in goldfish (Carassius auratus). LCT showed tissue-specific damage to gill, heart, liver and kidney tissues of goldfish. NMR profiling combined with statistical methods such as orthogonal partial least squares discriminant analysis (OPLS-DA) and two-dimensional statistical total correlation spectroscopy (2D-STOCSY) was developed to discern metabolite changes occurring after one week LCT exposure in brain, heart and kidney tissues of goldfish. LCT exposure influenced levels of many metabolites (e.g., leucine, isoleucine and valine in brain and kidney; lactate in brain, heart and kidney; alanine in brain and kidney; choline in brain, heart and kidney; taurine in brain, heart and kidney; N-acetylaspartate in brain; myo-inositol in brain; phosphocreatine in brain and heart; 2-oxoglutarate in brain; cis-aconitate in brain, and etc.), and broke the balance of neurotransmitters and osmoregulators, evoked oxidative stress, disturbed metabolisms of energy and amino acids. The implication of glutamate-glutamine-gamma-aminobutyric axis in LCT induced toxicity was demonstrated for the first time. Our findings demonstrated the applicability and potential of metabolomics approach for the elucidation of toxicological effects of pesticides and the underlying mechanisms, and the discovery of biomarkers for pesticide pollution in aquatic environment. Copyright © 2013 Elsevier B.V. All rights reserved.

Professional fighters brain health study: rationale and methods.

PubMed

Bernick, Charles; Banks, Sarah; Phillips, Michael; Lowe, Mark; Shin, Wanyong; Obuchowski, Nancy; Jones, Stephen; Modic, Michael

2013-07-15

Repetitive head trauma is a risk factor for Alzheimer's disease and is the primary cause of chronic traumatic encephalopathy. However, little is known about the natural history of, and risk factors for, chronic traumatic encephalopathy or about means of early detection and intervention. The Professional Fighters Brain Health Study is a longitudinal study of active professional fighters (boxers and mixed martial artists), retired professional fighters, and controls matched for age and level of education. The main objective of the Professional Fighters Brain Health Study is to determine the relationships between measures of head trauma exposure and other potential modifiers and changes in brain imaging and neurological and behavioral function over time. The study is designed to extend over 5 years, and we anticipate enrollment of more than 400 boxers and mixed martial artists. Participants will undergo annual evaluations that include 3-tesla magnetic resonance imaging scanning, computerized cognitive assessments, speech analysis, surveys of mood and impulsivity, and blood sampling for genotyping and exploratory biomarker studies. Statistical models will be developed and validated to predict early and progressive changes in brain structure and function. A composite fight exposure index, developed as a summary measure of cumulative traumatic exposure, shows promise as a predictor of brain volumes and cognitive function.

Nanotechnology-Based Strategies for siRNA Brain Delivery for Disease Therapy.

PubMed

Zheng, Meng; Tao, Wei; Zou, Yan; Farokhzad, Omid C; Shi, Bingyang

2018-05-01

Small interfering RNA (siRNA)-based gene silencing technology has demonstrated significant potential for treating brain-associated diseases. However, effective and safe systemic delivery of siRNA into the brain remains challenging because of biological barriers such as enzymatic degradation, short circulation lifetime, the blood-brain barrier (BBB), insufficient tissue penetration, cell endocytosis, and cytosolic transport. Nanotechnology offers intriguing potential for addressing these challenges in siRNA brain delivery in conjunction with chemical and biological modification strategies. In this review, we outline the challenges of systemic delivery of siRNA-based therapy for brain diseases, highlight recent advances in the development and engineering of siRNA nanomedicines for various brain diseases, and discuss our perspectives on this exciting research field for siRNA-based therapy towards more effective brain disease therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Oscillatory frontal theta responses are increased upon bisensory stimulation.

PubMed

Sakowitz, O W; Schürmann, M; Başar, E

2000-05-01

To investigate the functional correlation of oscillatory EEG components with the interaction of sensory modalities following simultaneous audio-visual stimulation. In an experimental study (15 subjects) we compared auditory evoked potentials (AEPs) and visual evoked potentials (VEPs) to bimodal evoked potentials (BEPs; simultaneous auditory and visual stimulation). BEPs were assumed to be brain responses to complex stimuli as a marker for intermodal associative functioning. Frequency domain analysis of these EPs showed marked theta-range components in response to bimodal stimulation. These theta components could not be explained by linear addition of the unimodal responses in the time domain. Considering topography the increased theta-response showed a remarkable frontality in proximity to multimodal association cortices. Referring to methodology we try to demonstrate that, even if various behavioral correlates of brain oscillations exist, common patterns can be extracted by means of a systems-theoretical approach. Serving as an example of functionally relevant brain oscillations, theta responses could be interpreted as an indicator of associative information processing.

Training-related changes in early visual processing of functionally illiterate adults: evidence from event-related brain potentials

PubMed Central

2013-01-01

Background Event-related brain potentials (ERPs) were used to investigate training-related changes in fast visual word recognition of functionally illiterate adults. Analyses focused on the left-lateralized occipito-temporal N170, which represents the earliest processing of visual word forms. Event-related brain potentials were recorded from 20 functional illiterates receiving intensive literacy training for adults, 10 functional illiterates not participating in the training and 14 regular readers while they read words, pseudowords or viewed symbol strings. Subjects were required to press a button whenever a stimulus was immediately repeated. Results Attending intensive literacy training was associated with improvements in reading and writing skills and with an increase of the word-related N170 amplitude. For untrained functional illiterates and regular readers no changes in literacy skills or N170 amplitude were observed. Conclusions Results of the present study suggest that the word-related N170 can still be modulated in adulthood as a result of the improvements in literacy skills. PMID:24330622

Polyphenols journey through blood-brain barrier towards neuronal protection.

PubMed

Figueira, I; Garcia, G; Pimpão, R C; Terrasso, A P; Costa, I; Almeida, A F; Tavares, L; Pais, T F; Pinto, P; Ventura, M R; Filipe, A; McDougall, G J; Stewart, D; Kim, K S; Palmela, I; Brites, D; Brito, M A; Brito, C; Santos, C N

2017-09-13

Age-related complications such as neurodegenerative disorders are increasing and remain cureless. The possibility of altering the progression or the development of these multifactorial diseases through diet is an emerging and attractive approach with increasing experimental support. We examined the potential of known bioavailable phenolic sulfates, arising from colonic metabolism of berries, to influence hallmarks of neurodegenerative processes. In silico predictions and in vitro transport studies across blood-brain barrier (BBB) endothelial cells, at circulating concentrations, provided evidence for differential transport, likely related to chemical structure. Moreover, endothelial metabolism of these phenolic sulfates produced a plethora of novel chemical entities with further potential bioactivies. Pre-conditioning with phenolic sulfates improved cellular responses to oxidative, excitotoxicity and inflammatory injuries and this attenuation of neuroinflammation was achieved via modulation of NF-κB pathway. Our results support the hypothesis that these small molecules, derived from dietary (poly)phenols may cross the BBB, reach brain cells, modulate microglia-mediated inflammation and exert neuroprotective effects, with potential for alleviation of neurodegenerative diseases.

Training-related changes in early visual processing of functionally illiterate adults: evidence from event-related brain potentials.

PubMed

Boltzmann, Melanie; Rüsseler, Jascha

2013-12-13

Event-related brain potentials (ERPs) were used to investigate training-related changes in fast visual word recognition of functionally illiterate adults. Analyses focused on the left-lateralized occipito-temporal N170, which represents the earliest processing of visual word forms. Event-related brain potentials were recorded from 20 functional illiterates receiving intensive literacy training for adults, 10 functional illiterates not participating in the training and 14 regular readers while they read words, pseudowords or viewed symbol strings. Subjects were required to press a button whenever a stimulus was immediately repeated. Attending intensive literacy training was associated with improvements in reading and writing skills and with an increase of the word-related N170 amplitude. For untrained functional illiterates and regular readers no changes in literacy skills or N170 amplitude were observed. Results of the present study suggest that the word-related N170 can still be modulated in adulthood as a result of the improvements in literacy skills.

Matrix metalloproteinases in the brain and blood–brain barrier: Versatile breakers and makers

PubMed Central

Rempe, Ralf G; Hartz, Anika MS

2016-01-01

Matrix metalloproteinases are versatile endopeptidases with many different functions in the body in health and disease. In the brain, matrix metalloproteinases are critical for tissue formation, neuronal network remodeling, and blood–brain barrier integrity. Many reviews have been published on matrix metalloproteinases before, most of which focus on the two best studied matrix metalloproteinases, the gelatinases MMP-2 and MMP-9, and their role in one or two diseases. In this review, we provide a broad overview of the role various matrix metalloproteinases play in brain disorders. We summarize and review current knowledge and understanding of matrix metalloproteinases in the brain and at the blood–brain barrier in neuroinflammation, multiple sclerosis, cerebral aneurysms, stroke, epilepsy, Alzheimer’s disease, Parkinson’s disease, and brain cancer. We discuss the detrimental effects matrix metalloproteinases can have in these conditions, contributing to blood–brain barrier leakage, neuroinflammation, neurotoxicity, demyelination, tumor angiogenesis, and cancer metastasis. We also discuss the beneficial role matrix metalloproteinases can play in neuroprotection and anti-inflammation. Finally, we address matrix metalloproteinases as potential therapeutic targets. Together, in this comprehensive review, we summarize current understanding and knowledge of matrix metalloproteinases in the brain and at the blood–brain barrier in brain disorders. PMID:27323783

Online adaptation of a c-VEP Brain-computer Interface(BCI) based on error-related potentials and unsupervised learning.

PubMed

Spüler, Martin; Rosenstiel, Wolfgang; Bogdan, Martin

2012-01-01

The goal of a Brain-Computer Interface (BCI) is to control a computer by pure brain activity. Recently, BCIs based on code-modulated visual evoked potentials (c-VEPs) have shown great potential to establish high-performance communication. In this paper we present a c-VEP BCI that uses online adaptation of the classifier to reduce calibration time and increase performance. We compare two different approaches for online adaptation of the system: an unsupervised method and a method that uses the detection of error-related potentials. Both approaches were tested in an online study, in which an average accuracy of 96% was achieved with adaptation based on error-related potentials. This accuracy corresponds to an average information transfer rate of 144 bit/min, which is the highest bitrate reported so far for a non-invasive BCI. In a free-spelling mode, the subjects were able to write with an average of 21.3 error-free letters per minute, which shows the feasibility of the BCI system in a normal-use scenario. In addition we show that a calibration of the BCI system solely based on the detection of error-related potentials is possible, without knowing the true class labels.

Hypoxic stress up-regulates Kir2.1 expression and facilitates cell proliferation in brain capillary endothelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamamura, Hideto; Suzuki, Yoshiaki; Yamamura, Hisao

The blood-brain barrier (BBB) is mainly composed of brain capillary endothelial cells (BCECs), astrocytes and pericytes. Brain ischemia causes hypoxic encephalopathy and damages BBB. However, it remains still unclear how hypoxia affects BCECs. In the present study, t-BBEC117 cells, an immortalized bovine brain endothelial cell line, were cultured under hypoxic conditions at 4–5% oxygen for 72 h. This hypoxic stress caused hyperpolarization of resting membrane potential. Patch-clamp recordings revealed a marked increase in Ba{sup 2+}-sensitive inward rectifier K{sup +} current in t-BBEC117 cells after hypoxic culture. Western blot and real-time PCR analyses showed that Kir2.1 expression was significantly up-regulated at protein level butmore » not at mRNA level after the hypoxic culture. Ca{sup 2+} imaging study revealed that the hypoxic stress enhanced store-operated Ca{sup 2+} (SOC) entry, which was significantly reduced in the presence of 100 μM Ba{sup 2+}. On the other hand, the expression of SOC channels such as Orai1, Orai2, and transient receptor potential channels was not affected by hypoxic stress. MTT assay showed that the hypoxic stress significantly enhanced t-BBEC117 cell proliferation, which was inhibited by approximately 60% in the presence of 100 μM Ba{sup 2+}. We first show here that moderate cellular stress by cultivation under hypoxic conditions hyperpolarizes membrane potential via the up-regulation of functional Kir2.1 expression and presumably enhances Ca{sup 2+} entry, resulting in the facilitation of BCEC proliferation. These findings suggest potential roles of Kir2.1 expression in functional changes of BCECs in BBB following ischemia. -- Highlights: •Hypoxic culture of brain endothelial cells (BEC) caused membrane hyperpolarization. •This hyperpolarization was due to the increased expression of Kir2.1 channels. •Hypoxia enhanced store-operated Ca{sup 2+} (SOC) entry via Kir2.1 up-regulation. •Expression levels of putative SOC channels were not affected by hypoxia. •Kir2.1 up-regulation is responsible for hypoxia-enhanced BEC proliferation.« less

Pain-related somatosensory evoked potentials and functional brain magnetic resonance in the evaluation of neurologic recovery after cardiac arrest: a case study of three patients.

PubMed

Zanatta, Paolo; Messerotti Benvenuti, Simone; Baldanzi, Fabrizio; Bendini, Matteo; Saccavini, Marsilio; Tamari, Wadih; Palomba, Daniela; Bosco, Enrico

2012-03-31

This case series investigates whether painful electrical stimulation increases the early prognostic value of both somatosensory-evoked potentials and functional magnetic resonance imaging in comatose patients after cardiac arrest. Three single cases with hypoxic-ischemic encephalopathy were considered. A neurophysiological evaluation with an electroencephalogram and somatosensory-evoked potentials during increased electrical stimulation in both median nerves was performed within five days of cardiac arrest. Each patient also underwent a functional magnetic resonance imaging evaluation with the same neurophysiological protocol one month after cardiac arrest. One patient, who completely recovered, showed a middle latency component at a high intensity of stimulation and the activation of all brain areas involved in cerebral pain processing. One patient in a minimally conscious state only showed the cortical somatosensory response and the activation of the primary somatosensory cortex. The last patient, who was in a vegetative state, did not show primary somatosensory evoked potentials; only the activation of subcortical brain areas occurred. These preliminary findings suggest that the pain-related somatosensory evoked potentials performed to increase the prognosis of comatose patients after cardiac arrest are associated with regional brain activity showed by functional magnetic resonance imaging during median nerves electrical stimulation. More importantly, this cases report also suggests that somatosensory evoked potentials and functional magnetic resonance imaging during painful electrical stimulation may be sensitive and complementary methods to predict the neurological outcome in the acute phase of coma. Thus, pain-related somatosensory-evoked potentials may be a reliable and a cost-effective tool for planning the early diagnostic evaluation of comatose patients.

Employment outcome four years after a severe traumatic brain injury: results of the Paris severe traumatic brain injury study.

PubMed

Ruet, Alexis; Jourdan, Claire; Bayen, Eléonore; Darnoux, Emmanuelle; Sahridj, Dalila; Ghout, Idir; Azerad, Sylvie; Pradat Diehl, Pascale; Aegerter, Philippe; Charanton, James; Vallat Azouvi, Claire; Azouvi, Philippe

2017-05-18

To describe employment outcome four years after a severe traumatic brain injury by the assessment of individual patients' preinjury sociodemographic data, injury-related and postinjury factors. A prospective, multicenter inception cohort of 133 adult patients in the Paris area (France) who had received a severe traumatic brain injury were followed up postinjury at one and four years. Sociodemographic data, factors related to injury severity and one-year functional and cognitive outcomes were prospectively collected. The main outcome measure was employment status. Potential predictors of employment status were assessed by univariate and multivariate analysis. At the four-year follow-up, 38% of patients were in paid employment. The following factors were independent predictors of unemployment: being unemployed or studying before traumatic brain injury, traumatic brain injury severity (i.e., a lower Glasgow Coma Scale score upon admission and a longer stay in intensive care) and a lower one-year Glasgow Outcome Scale-Extended score. This study confirmed the low rate of long-term employment amongst patients after a severe traumatic brain injury. The results illustrated the multiple determinants of employment outcome and suggested that students who had received a traumatic brain injury were particularly likely to be unemployed, thus we propose that they may require specific support to help them find work. Implications for rehabilitation Traumatic brain injury is a leading cause of persistent disablity and can associate cognitive, emotional, physical and sensory impairments, which often result in quality-of-life reduction and job loss. Predictors of post-traumatic brain injury unemployment and job loss remains unclear in the particular population of severe traumatic brain injury patients. The present study highlights the post-traumatic brain injury student population require a close follow-up and vocational rehabilitation. The study suggests that return to work post-severe traumatic brain injury is frequently unstable and workers often experience difficulties that caregivers have to consider.

Inflammation and white matter degeneration persist for years after a single traumatic brain injury.

PubMed

Johnson, Victoria E; Stewart, Janice E; Begbie, Finn D; Trojanowski, John Q; Smith, Douglas H; Stewart, William

2013-01-01

A single traumatic brain injury is associated with an increased risk of dementia and, in a proportion of patients surviving a year or more from injury, the development of hallmark Alzheimer's disease-like pathologies. However, the pathological processes linking traumatic brain injury and neurodegenerative disease remain poorly understood. Growing evidence supports a role for neuroinflammation in the development of Alzheimer's disease. In contrast, little is known about the neuroinflammatory response to brain injury and, in particular, its temporal dynamics and any potential role in neurodegeneration. Cases of traumatic brain injury with survivals ranging from 10 h to 47 years post injury (n = 52) and age-matched, uninjured control subjects (n = 44) were selected from the Glasgow Traumatic Brain Injury archive. From these, sections of the corpus callosum and adjacent parasaggital cortex were examined for microglial density and morphology, and for indices of white matter pathology and integrity. With survival of ≥3 months from injury, cases with traumatic brain injury frequently displayed extensive, densely packed, reactive microglia (CR3/43- and/or CD68-immunoreactive), a pathology not seen in control subjects or acutely injured cases. Of particular note, these reactive microglia were present in 28% of cases with survival of >1 year and up to 18 years post-trauma. In cases displaying this inflammatory pathology, evidence of ongoing white matter degradation could also be observed. Moreover, there was a 25% reduction in the corpus callosum thickness with survival >1 year post-injury. These data present striking evidence of persistent inflammation and ongoing white matter degeneration for many years after just a single traumatic brain injury in humans. Future studies to determine whether inflammation occurs in response to or, conversely, promotes white matter degeneration will be important. These findings may provide parallels for studying neurodegenerative disease, with traumatic brain injury patients serving as a model for longitudinal investigations, in particular with a view to identifying potential therapeutic interventions.

Comparative evaluation of methylene blue and demeclocycline for enhancing optical contrast of brain neoplasms

NASA Astrophysics Data System (ADS)

Wirth, Dennis J.

Brain tumors cause significant morbidity and mortality even when benign. Completeness of resection of brain tumors has been associated with better quality of life. However, that is often difficult to accomplish. The goal of this study was to evaluate the feasibility of using contrast enhanced multimodal confocal imaging for intraoperative detection of brain neoplasms. Different types of benign and malignant, primary and metastatic brain tumors, stained with Methylene Blue (MB) as a contrast agent, were imaged. MB is a traditional histopathologic stain that absorbs light in the red spectral range and fluoresces in the near infrared. It is FDA-approved for in vivo staining of human skin and breast tissue. Optical images showed good correlation with histopathology, demonstrating the potential of contrast enhanced multimodal confocal imaging for intraoperative detection of brain neoplasms ex vivo. However, the safety of MB for staining human brain in vivo is questionable. Demeclocycline (DMN), an antibiotic of the tetracycline family, has shown to be effective in differentiating normal from cancerous tissue in various organs. DMN is a fluorophore, which absorbs light in the violet spectral range and has a broad emission band covering green and yellow wavelengths. It is commonly used to treat infection and inflammatory disorders, and could provide a safer alternative to MB. To test this hypothesis, fresh excess human brain tissues were bisected and stained with aqueous solutions of either MB or DMN and then imaged. Reflectance and fluorescence images acquired from tissues stained with the two dyes were compared, and correlated with processed H&E histopathology. Comparison showed similar staining patterns and contrast of diagnostic features in glioblastomas, stained using either MB or DMN. The results show potential of both MB and DMN for the intraoperative detection of microscopic nests of brain neoplasms. Further studies will establish safety and efficacy of these agents in vivo.

Hydrogen sulfide therapy in brain diseases: from bench to bedside

PubMed Central

Zhang, Ju-yi; Ding, Yi-ping; Wang, Zhong; Kong, Yan; Gao, Rong; Chen, Gang

2017-01-01

Hydrogen sulfide (H2S) has been recognized and studied for nearly 300 years, but past researches mainly focus on its toxicity effect. During the past two decades, the majority of researches have reported that H2S is a novel endogenous gaseous signal molecule in organisms, and play an important role in various systems and diseases. H2S is mainly produced by three enzymes, including cystathionine β-synthase, cystathionine γ-lyase and 3-mercaptopyruvate sulfurtransferase along with cysteine aminotransferase. H2S had been firstly reported as a neuromodulator in the brain, because of its essential role in the facilitating hippocampal long-term potentiation at physiological concentration. It is subsequently reported that H2S may have relevance to neurologic disorders through antioxidative, anti-inflammatory, anti-apoptotic and additional effects. Recent basic medical studies and preclinical studies on neurologic diseases have demonstrated that the administration of H2S at physiological or pharmacological levels attenuates brain injury. However, the neuroprotective effect of H2S is concentration-dependent, only a comparatively low dose of H2S can provide beneficial effect. Herein, we review the neuroprotevtive role of H2S therapy in brain diseases from its mechanism to clinical application in animal and human subjects, and therefore provide the potential strategies for further clinical treatment. PMID:28744364

Identification of potential novel interaction partners of the sodium-activated potassium channels Slick and Slack in mouse brain.

PubMed

Rizzi, Sandra; Schwarzer, Christoph; Kremser, Leopold; Lindner, Herbert H; Knaus, Hans-Günther

2015-12-01

The sodium-activated potassium channels Slick (Slo2.1, KCNT2) and Slack (Slo2.2, KCNT1) are paralogous channels of the Slo family of high-conductance potassium channels. Slick and Slack channels are widely distributed in the mammalian CNS and they play a role in slow afterhyperpolarization, generation of depolarizing afterpotentials and in setting and stabilizing the resting potential. In the present study we used a combined approach of (co)-immunoprecipitation studies, Western blot analysis, double immunofluorescence and mass spectrometric sequencing in order to investigate protein-protein interactions of the Slick and Slack channels. The data strongly suggest that Slick and Slack channels co-assemble into identical cellular complexes. Double immunofluorescence experiments revealed that Slick and Slack channels co-localize in distinct mouse brain regions. Moreover, we identified the small cytoplasmic protein beta-synuclein and the transmembrane protein 263 (TMEM 263) as novel interaction partners of both, native Slick and Slack channels. In addition, the inactive dipeptidyl-peptidase (DPP 10) and the synapse associated protein 102 (SAP 102) were identified as constituents of the native Slick and Slack channel complexes in the mouse brain. This study presents new insights into protein-protein interactions of native Slick and Slack channels in the mouse brain.

Ischemic Brain Injury Leads to Brain Edema via Hyperthermia-Induced TRPV4 Activation.

PubMed

Hoshi, Yutaka; Okabe, Kohki; Shibasaki, Koji; Funatsu, Takashi; Matsuki, Norio; Ikegaya, Yuji; Koyama, Ryuta

2018-06-20

Brain edema is characterized by an increase in net brain water content, which results in an increase in brain volume. Although brain edema is associated with a high fatality rate, the cellular and molecular processes of edema remain largely unclear. Here, we developed an in vitro model of ischemic stroke-induced edema in which male mouse brain slices were treated with oxygen-glucose deprivation (OGD) to mimic ischemia. We continuously measured the cross-sectional area of the brain slice for 150 min under macroscopic microscopy, finding that OGD induces swelling of brain slices. OGD-induced swelling was prevented by pharmacologically blocking or genetically knocking out the transient receptor potential vanilloid 4 (TRPV4), a member of the thermosensitive TRP channel family. Because TRPV4 is activated at around body temperature and its activation is enhanced by heating, we next elevated the temperature of the perfusate in the recording chamber, finding that hyperthermia induces swelling via TRPV4 activation. Furthermore, using the temperature-dependent fluorescence lifetime of a fluorescent-thermosensitive probe, we confirmed that OGD treatment increases the temperature of brain slices through the activation of glutamate receptors. Finally, we found that brain edema following traumatic brain injury was suppressed in TRPV4-deficient male mice in vivo Thus, our study proposes a novel mechanism: hyperthermia activates TRPV4 and induces brain edema after ischemia. SIGNIFICANCE STATEMENT Brain edema is characterized by an increase in net brain water content, which results in an increase in brain volume. Although brain edema is associated with a high fatality rate, the cellular and molecular processes of edema remain unclear. Here, we developed an in vitro model of ischemic stroke-induced edema in which mouse brain slices were treated with oxygen-glucose deprivation. Using this system, we showed that the increase in brain temperature and the following activation of the thermosensitive cation channel TRPV4 (transient receptor potential vanilloid 4) are involved in the pathology of edema. Finally, we confirmed that TRPV4 is involved in brain edema in vivo using TRPV4-deficient mice, concluding that hyperthermia activates TRPV4 and induces brain edema after ischemia. Copyright © 2018 the authors 0270-6474/18/385700-10$15.00/0.

Event-related potential markers of brain changes in preclinical familial Alzheimer disease

PubMed Central

Ally, B.A.; Celone, K.; McKeever, J.; Ruiz-Rizzo, A.L.; Lopera, F.; Stern, C.E.; Budson, A.E.

2011-01-01

Objectives: Event-related potentials (ERPs) can reflect differences in brain electrophysiology underlying cognitive functions in brain disorders such as dementia and mild cognitive impairment. To identify individuals at risk for Alzheimer disease (AD) we used high-density ERPs to examine brain physiology in young presymptomatic individuals (average age 34.2 years) who carry the E280A mutation in the presenilin-1 (PSEN1) gene and will go on to develop AD around the age of 45. Methods: Twenty-one subjects from a Colombian population with familial AD participated: 10 presymptomatic subjects positive for the PSEN1 mutation (carriers) and 11 siblings without the mutation (controls). Subjects performed a visual recognition memory test while 128-channel ERPs were recorded. Results: Despite identical behavioral performance, PSEN1 mutation carriers showed less positivity in frontal regions and more positivity in occipital regions, compared to controls. These differences were more pronounced during the 200–300 msec period. Discriminant analysis at this time interval showed promising sensitivity (72.7%) and specificity (81.8%) of the ERP measures to predict the presence of AD pathology. Conclusions: Presymptomatic PSEN1 mutation carriers show changes in brain physiology that can be detected by high-density ERPs. The relative differences observed showing greater frontal positivity in controls and greater occipital positivity in carriers indicates that control subjects may use frontally mediated processes to distinguish between studied and unstudied visual items, whereas carriers appear to rely more upon perceptual details of the items to distinguish between them. These findings also demonstrate the potential usefulness of ERP brain correlates as preclinical markers of AD. PMID:21775732

Error-Related Brain Activity in Young Children: Associations with Parental Anxiety and Child Temperamental Negative Emotionality

ERIC Educational Resources Information Center

Torpey, Dana C.; Hajcak, Greg; Kim, Jiyon; Kujawa, Autumn J.; Dyson, Margaret W.; Olino, Thomas M.; Klein, Daniel N.

2013-01-01

Background: There is increasing interest in error-related brain activity in anxiety disorders. The error-related negativity (ERN) is a negative deflection in the event-related potential approximately 50 [milliseconds] after errors compared to correct responses. Recent studies suggest that the ERN may be a biomarker for anxiety, as it is positively…

Brain-Derived Neurotrophic Factor Gene Expression in Pediatric Bipolar Disorder: Effects of Treatment and Clinical Response

ERIC Educational Resources Information Center

Pandey, Ghanshyam N.; Rizavi, Hooriyah S.; Dwivedi, Yogesh; Pavuluri, Mani N.

2008-01-01

The study determines the gene expression of brain-derived neurotrophic factor (BDNF) in the lymphocytes of subjects with pediatric bipolar disorder (PBD) before and during treatment with mood stabilizers and in drug-free normal control subjects. Results indicate the potential of BDNF levels as a biomarker for PBD and as a treatment predictor and…

Novice Teachers' Perceptions of Their Preparation and Efficacy to Teach Students with Traumatic Brain Injury

ERIC Educational Resources Information Center

Armstrong, Theresa Sacchi

2017-01-01

After a brain injury, children often return to school with complex learning needs. Most special educators receive little specific preparation relating to TBI and may lack the experience to assist children to reach their full potential. This study examined novice teachers' perceptions of the value of the academic and in-service professional…

Coronal in vivo forward-imaging of rat brain morphology with an ultra-small optical coherence tomography fiber probe

NASA Astrophysics Data System (ADS)

Xie, Yijing; Bonin, Tim; Löffler, Susanne; Hüttmann, Gereon; Tronnier, Volker; Hofmann, Ulrich G.

2013-02-01

A well-established navigation method is one of the key conditions for successful brain surgery: it should be accurate, safe and online operable. Recent research shows that optical coherence tomography (OCT) is a potential solution for this application by providing a high resolution and small probe dimension. In this study a fiber-based spectral-domain OCT system utilizing a super-luminescent-diode with the center wavelength of 840 nm providing 14.5 μm axial resolution was used. A composite 125 μm diameter detecting probe with a gradient index (GRIN) fiber fused to a single mode fiber was employed. Signals were reconstructed into grayscale images by horizontally aligning A-scans from the same trajectory with different depths. The reconstructed images can display brain morphology along the entire trajectory. For scans of typical white matter, the signals showed a higher reflection of light intensity with lower penetration depth as well as a steeper attenuation rate compared to the scans typical for gray matter. Micro-structures such as axon bundles (70 μm) in the caudate nucleus are visible in the reconstructed images. This study explores the potential of OCT to be a navigation modality in brain surgery.

Study of plasma-derived miRNAs mimic differences in Huntington's disease brain.

PubMed

Hoss, Andrew G; Lagomarsino, Valentina N; Frank, Samuel; Hadzi, Tiffany C; Myers, Richard H; Latourelle, Jeanne C

2015-12-01

Biomarkers for Huntington's disease progression could accelerate therapeutic developments and improve patient care. Brain microRNAs relating to clinical features of Huntington's disease may represent a potential Huntington's disease biomarker in blood. This study was undertaken to examine candidate microRNAs in plasma to determine whether changes observed in HD brains are detectable in peripheral samples. Four microRNAs from 26 manifest Huntington's disease, four asymptomatic Huntington's disease gene carriers, and eight controls were quantified in plasma using reverse transcription quantitative polymerase chain reaction. Linear regression was used to assess microRNA levels across control, asymptomatic gene carriers, and manifest patients. miR-10b-5p (P = 0.0068) and miR-486-5p (P = 0.044) were elevated in Huntington's disease plasma. miR-10b-5p was decreased in asymptomatic gene carriers as compared with patients with Huntington's disease (P = 0.049), but no difference between asymptomatic gene carriers and healthy controls was observed (P = 0.24). These findings suggest that microRNA changes observed in Huntington's disease brain may be detectable in plasma and have potential clinical utility. © 2015 International Parkinson and Movement Disorder Society.

Dromosagnosia, or why some people lose their sense of direction while driving.

PubMed

Tseng, Wei-Shih; Tzeng, Nian-Sheng

2013-11-01

We coined a new word, "dromosagnosia", from the Greek words, dromos ("way, road")+agnosia, to describe the loss of direction while driving, an orientation disorder similar to but different from pure topographic disorientation. Historically, human beings have moved more quickly, from using domesticated animals to high speed vehicles, and this may be beyond the brain's ability to react. Without the benefit of an automatic navigation system, automobiles are associated with more problems of dromosagnosia than are fast-moving aircraft or ships. Previous studies have noted that some areas of the brain are associated with spatial orientation, spatial memory, and even emotion, and abnormalities there could exacerbate the loss of sense of direction. We hypothesize that some people are especially disadvantaged from these brain differences and emotional disturbances when driving their cars. Functional magnetic resonance imaging (fMRI) and event-related potentials (ERP) studies combined with a virtual reality driving simulation might be used to find the areas of the brain related to dromosagnosia. Future applications: some people with dromosagnosia might benefit from special remedial training and a driving safety support system to avoid potential problems. Copyright © 2013 Elsevier Ltd. All rights reserved.

Joint Maximum Likelihood Time Delay Estimation of Unknown Event-Related Potential Signals for EEG Sensor Signal Quality Enhancement

PubMed Central

Kim, Kyungsoo; Lim, Sung-Ho; Lee, Jaeseok; Kang, Won-Seok; Moon, Cheil; Choi, Ji-Woong

2016-01-01

Electroencephalograms (EEGs) measure a brain signal that contains abundant information about the human brain function and health. For this reason, recent clinical brain research and brain computer interface (BCI) studies use EEG signals in many applications. Due to the significant noise in EEG traces, signal processing to enhance the signal to noise power ratio (SNR) is necessary for EEG analysis, especially for non-invasive EEG. A typical method to improve the SNR is averaging many trials of event related potential (ERP) signal that represents a brain’s response to a particular stimulus or a task. The averaging, however, is very sensitive to variable delays. In this study, we propose two time delay estimation (TDE) schemes based on a joint maximum likelihood (ML) criterion to compensate the uncertain delays which may be different in each trial. We evaluate the performance for different types of signals such as random, deterministic, and real EEG signals. The results show that the proposed schemes provide better performance than other conventional schemes employing averaged signal as a reference, e.g., up to 4 dB gain at the expected delay error of 10°. PMID:27322267

Evaluation of blood-brain barrier-stealth nanocomposites for in situ glioblastoma theranostics applications

NASA Astrophysics Data System (ADS)

Su, Chia-Hao; Tsai, Ching-Yi; Tomanek, Boguslaw; Chen, Wei-Yu; Cheng, Fong-Yu

2016-04-01

The blood-brain barrier (BBB) is a physiological structure of the blood vessels in the brain. The BBB efficiently traps most therapeutic drugs in the blood vessels and stops them from entering the brain tissue, resulting in a decreased therapeutic efficiency. In this study, we developed BBB-stealth nanocomposites composed of iron oxide (Fe3O4) nanoparticles (NPs) as a safe nanocarrier for glioblastoma therapy. We showed the antitumor activity of Dox/alg-Fe3O4 NPs using in vitro and in vivo tests. We demonstrated that G23-alg-Fe3O4 NPs crossed the BBB and entered the brain. In situ glioblastoma tumor-bearing mice were used to successfully evaluate the antitumor activity of G23-Dox/alg-Fe3O4 NPs. Magnetic resonance imaging (MRI) and bioluminescence imaging (BLI) confirmed the BBB crossing. The BBB-stealth nanocomposites show great potential for a proof-of-concept clinical trial as a theranostics platform for human brain tumor therapy.The blood-brain barrier (BBB) is a physiological structure of the blood vessels in the brain. The BBB efficiently traps most therapeutic drugs in the blood vessels and stops them from entering the brain tissue, resulting in a decreased therapeutic efficiency. In this study, we developed BBB-stealth nanocomposites composed of iron oxide (Fe3O4) nanoparticles (NPs) as a safe nanocarrier for glioblastoma therapy. We showed the antitumor activity of Dox/alg-Fe3O4 NPs using in vitro and in vivo tests. We demonstrated that G23-alg-Fe3O4 NPs crossed the BBB and entered the brain. In situ glioblastoma tumor-bearing mice were used to successfully evaluate the antitumor activity of G23-Dox/alg-Fe3O4 NPs. Magnetic resonance imaging (MRI) and bioluminescence imaging (BLI) confirmed the BBB crossing. The BBB-stealth nanocomposites show great potential for a proof-of-concept clinical trial as a theranostics platform for human brain tumor therapy. Electronic supplementary information (ESI) available: Experimental details. See DOI: 10.1039/c6nr00280c

Glutamate-Mediated Blood-Brain Barrier Opening: Implications for Neuroprotection and Drug Delivery.

PubMed

Vazana, Udi; Veksler, Ronel; Pell, Gaby S; Prager, Ofer; Fassler, Michael; Chassidim, Yoash; Roth, Yiftach; Shahar, Hamutal; Zangen, Abraham; Raccah, Ruggero; Onesti, Emanuela; Ceccanti, Marco; Colonnese, Claudio; Santoro, Antonio; Salvati, Maurizio; D'Elia, Alessandro; Nucciarelli, Valter; Inghilleri, Maurizio; Friedman, Alon

2016-07-20

The blood-brain barrier is a highly selective anatomical and functional interface allowing a unique environment for neuro-glia networks. Blood-brain barrier dysfunction is common in most brain disorders and is associated with disease course and delayed complications. However, the mechanisms underlying blood-brain barrier opening are poorly understood. Here we demonstrate the role of the neurotransmitter glutamate in modulating early barrier permeability in vivo Using intravital microscopy, we show that recurrent seizures and the associated excessive glutamate release lead to increased vascular permeability in the rat cerebral cortex, through activation of NMDA receptors. NMDA receptor antagonists reduce barrier permeability in the peri-ischemic brain, whereas neuronal activation using high-intensity magnetic stimulation increases barrier permeability and facilitates drug delivery. Finally, we conducted a double-blind clinical trial in patients with malignant glial tumors, using contrast-enhanced magnetic resonance imaging to quantitatively assess blood-brain barrier permeability. We demonstrate the safety of stimulation that efficiently increased blood-brain barrier permeability in 10 of 15 patients with malignant glial tumors. We suggest a novel mechanism for the bidirectional modulation of brain vascular permeability toward increased drug delivery and prevention of delayed complications in brain disorders. In this study, we reveal a new mechanism that governs blood-brain barrier (BBB) function in the rat cerebral cortex, and, by using the discovered mechanism, we demonstrate bidirectional control over brain endothelial permeability. Obviously, the clinical potential of manipulating BBB permeability for neuroprotection and drug delivery is immense, as we show in preclinical and proof-of-concept clinical studies. This study addresses an unmet need to induce transient BBB opening for drug delivery in patients with malignant brain tumors and effectively facilitate BBB closure in neurological disorders. Copyright © 2016 the authors 0270-6474/16/367727-13$15.00/0.

Glutamate-Mediated Blood–Brain Barrier Opening: Implications for Neuroprotection and Drug Delivery

PubMed Central

Vazana, Udi; Veksler, Ronel; Pell, Gaby S.; Prager, Ofer; Fassler, Michael; Chassidim, Yoash; Roth, Yiftach; Shahar, Hamutal; Zangen, Abraham; Raccah, Ruggero; Onesti, Emanuela; Ceccanti, Marco; Colonnese, Claudio; Santoro, Antonio; Salvati, Maurizio; D'Elia, Alessandro; Nucciarelli, Valter; Inghilleri, Maurizio

2016-01-01

The blood–brain barrier is a highly selective anatomical and functional interface allowing a unique environment for neuro-glia networks. Blood–brain barrier dysfunction is common in most brain disorders and is associated with disease course and delayed complications. However, the mechanisms underlying blood–brain barrier opening are poorly understood. Here we demonstrate the role of the neurotransmitter glutamate in modulating early barrier permeability in vivo. Using intravital microscopy, we show that recurrent seizures and the associated excessive glutamate release lead to increased vascular permeability in the rat cerebral cortex, through activation of NMDA receptors. NMDA receptor antagonists reduce barrier permeability in the peri-ischemic brain, whereas neuronal activation using high-intensity magnetic stimulation increases barrier permeability and facilitates drug delivery. Finally, we conducted a double-blind clinical trial in patients with malignant glial tumors, using contrast-enhanced magnetic resonance imaging to quantitatively assess blood–brain barrier permeability. We demonstrate the safety of stimulation that efficiently increased blood–brain barrier permeability in 10 of 15 patients with malignant glial tumors. We suggest a novel mechanism for the bidirectional modulation of brain vascular permeability toward increased drug delivery and prevention of delayed complications in brain disorders. SIGNIFICANCE STATEMENT In this study, we reveal a new mechanism that governs blood–brain barrier (BBB) function in the rat cerebral cortex, and, by using the discovered mechanism, we demonstrate bidirectional control over brain endothelial permeability. Obviously, the clinical potential of manipulating BBB permeability for neuroprotection and drug delivery is immense, as we show in preclinical and proof-of-concept clinical studies. This study addresses an unmet need to induce transient BBB opening for drug delivery in patients with malignant brain tumors and effectively facilitate BBB closure in neurological disorders. PMID:27445149

Brain Drain: A Child's Brain on Poverty. Poverty Fact Sheet

ERIC Educational Resources Information Center

Damron, Neil

2015-01-01

"Brain Drain: A Child's Brain on Poverty," released in March 2015 and prepared by intern Neil Damron, explores the brain's basic anatomy and recent research findings suggesting that poverty affects the brain development of infants and young children and the potential lifelong effects of the changes. The sheet draws from a variety of…

Population based MRI and DTI templates of the adult ferret brain and tools for voxelwise analysis.

PubMed

Hutchinson, E B; Schwerin, S C; Radomski, K L; Sadeghi, N; Jenkins, J; Komlosh, M E; Irfanoglu, M O; Juliano, S L; Pierpaoli, C

2017-05-15

Non-invasive imaging has the potential to play a crucial role in the characterization and translation of experimental animal models to investigate human brain development and disorders, especially when employed to study animal models that more accurately represent features of human neuroanatomy. The purpose of this study was to build and make available MRI and DTI templates and analysis tools for the ferret brain as the ferret is a well-suited species for pre-clinical MRI studies with folded cortical surface, relatively high white matter volume and body dimensions that allow imaging with pre-clinical MRI scanners. Four ferret brain templates were built in this study - in-vivo MRI and DTI and ex-vivo MRI and DTI - using brain images across many ferrets and region of interest (ROI) masks corresponding to established ferret neuroanatomy were generated by semi-automatic and manual segmentation. The templates and ROI masks were used to create a web-based ferret brain viewing software for browsing the MRI and DTI volumes with annotations based on the ROI masks. A second objective of this study was to provide a careful description of the imaging methods used for acquisition, processing, registration and template building and to demonstrate several voxelwise analysis methods including Jacobian analysis of morphometry differences between the female and male brain and bias-free identification of DTI abnormalities in an injured ferret brain. The templates, tools and methodological optimization presented in this study are intended to advance non-invasive imaging approaches for human-similar animal species that will enable the use of pre-clinical MRI studies for understanding and treating brain disorders. Published by Elsevier Inc.

Brain structure in sagittal craniosynostosis

NASA Astrophysics Data System (ADS)

Paniagua, Beatriz; Kim, Sunghyung; Moustapha, Mahmoud; Styner, Martin; Cody-Hazlett, Heather; Gimple-Smith, Rachel; Rumple, Ashley; Piven, Joseph; Gilmore, John; Skolnick, Gary; Patel, Kamlesh

2017-03-01

Craniosynostosis, the premature fusion of one or more cranial sutures, leads to grossly abnormal head shapes and pressure elevations within the brain caused by these deformities. To date, accepted treatments for craniosynostosis involve improving surgical skull shape aesthetics. However, the relationship between improved head shape and brain structure after surgery has not been yet established. Typically, clinical standard care involves the collection of diagnostic medical computed tomography (CT) imaging to evaluate the fused sutures and plan the surgical treatment. CT is known to provide very good reconstructions of the hard tissues in the skull but it fails to acquire good soft brain tissue contrast. This study intends to use magnetic resonance imaging to evaluate brain structure in a small dataset of sagittal craniosynostosis patients and thus quantify the effects of surgical intervention in overall brain structure. Very importantly, these effects are to be contrasted with normative shape, volume and brain structure databases. The work presented here wants to address gaps in clinical knowledge in craniosynostosis focusing on understanding the changes in brain volume and shape secondary to surgery, and compare those with normally developing children. This initial pilot study has the potential to add significant quality to the surgical care of a vulnerable patient population in whom we currently have limited understanding of brain developmental outcomes.

Enhanced permeability of blood-brain barrier and targeting function of brain via borneol-modified chemically solid lipid nanoparticle.

PubMed

Song, Hui; Wei, Man; Zhang, Nan; Li, He; Tan, Xiaochuan; Zhang, Yujia; Zheng, Wensheng

2018-01-01

The incidence of central nervous system disease has increased in recent years. However, the transportation of drug is restricted by the blood-brain barrier, contributing to the poor therapeutic effect in the brain. Therefore, the development of a new brain-targeting drug delivery system has become the hotspot of pharmacy. Borneol, a simple bicyclic monoterpene extracted from Dryobalanops aromatica , can direct drugs to the upper body parts according to the theory of traditional Chinese medicine. Dioleoyl phosphoethanolamine (DOPE) was chemically modified by borneol as one of the lipid materials of solid lipid nanoparticle (SLN) in the present study. The borneol-modified chemically solid lipid nanoparticle (BO-SLN/CM), borneol-modified physically solid lipid nanoparticle (BO-SLN/PM), and SLN have similar diameter (of about 87 nm) and morphological characteristics. However, BO-SLN/CM has a lower cytotoxicity, higher cell uptake, and better blood-brain barrier permeability compared with BO-SLN/PM and SLN. BO-SLN/CM has a remarkable targeting function to the brain, while BO-SLN/ PM and SLNs are concentrated at the lung. The present study provides an excellent drug delivery carrier, BO-SLN/CM, having the application potential of targeting to the brain and permeating to the blood-brain barrier.

The Etiology of Cirrhosis is a Strong Determinant of Brain Reserve: A Multi-modal MR Imaging Study

PubMed Central

Ahluwalia, Vishwadeep; Wade, James B; Moeller, F Gerard; White, Melanie B; Unser, Ariel B; Gavis, Edith A; Sterling, Richard K; Stravitz, R Todd; Sanyal, Arun J; Siddiqui, Mohammad S; Puri, Puneet; Luketic, Velimir; Heuman, Douglas M; Fuchs, Michael; Matherly, Scott; Bajaj, Jasmohan S

2015-01-01

Background Poor brain reserve in alcoholic cirrhosis could worsen insight regarding disease severity and increase the patients’ vulnerability towards further deterioration. Aim To analyze brain reserve in abstinent alcoholic (Alc) compared to non-alcoholic (Nalc) cirrhosis patients in the context of hepatic encephalopathy (HE) and evaluate relative change in brain reserve between groups over time and before/after elective TIPS placement. Methods Cross-sectional study 46 Alc and 102 Nalc outpatients with or without HE. Cognitive tests followed by magnetic resonance (MR) imaging including 1-H MR Spectroscopy (MRS), Diffusion tensor (DTI) and T1-weighted imaging. Prospective study MRS on subset of 10 patients before/after TIPS placement. Another subset of 26 patients underwent MRS at least one year apart. Results Cross-sectional study Alc patients were worse on cognitive tests than Nalc. MR results suggest a greater effect of hyperammonemia, brain edema and significantly higher cortical damage in Alc as compared to Nalc patients. Effect of HE status on cognitive tests and brain reserve was more marked in Nalc than in Alc group. TIPS study Nalc patients showed a greater adverse relative change after TIPS compared to Alc group. 1-year follow-up Both groups remained stable between the two visits. However, Alc patients continued to show poor brain reserve than Nalc over time. Conclusions Patients with alcoholic cirrhosis, despite abstinence, have a poor brain reserve while, non-alcoholic cirrhosis patients have a greater potential for brain reserve deterioration after HE and TIPS. Information regarding the brain reserve in cirrhosis could assist medical teams to refine their communication and monitoring strategies for different etiologies. PMID:25939692

Simulation study of a high performance brain PET system with dodecahedral geometry.

PubMed

Tao, Weijie; Chen, Gaoyu; Weng, Fenghua; Zan, Yunlong; Zhao, Zhixiang; Peng, Qiyu; Xu, Jianfeng; Huang, Qiu

2018-05-25

In brain imaging, the spherical PET system achieves the highest sensitivity when the solid angle is concerned. However it is not practical. In this work we designed an alternative sphere-like scanner, the dodecahedral scanner, which has a high sensitivity in imaging and a high feasibility to manufacture. We simulated this system and compared the performance with a few other dedicated brain PET systems. Monte Carlo simulations were conducted to generate data of the dedicated brain PET system with the dodecahedral geometry (11 regular pentagon detectors). The data were then reconstructed using the in-house developed software with the fully three-dimensional maximum-likelihood expectation maximization (3D-MLEM) algorithm. Results show that the proposed system has a high sensitivity distribution for the whole field of view (FOV). With a depth-of-interaction (DOI) resolution around 6.67 mm, the proposed system achieves the spatial resolution of 1.98 mm. Our simulation study also shows that the proposed system improves the image contrast and reduces noise compared with a few other dedicated brain PET systems. Finally, simulations with the Hoffman phantom show the potential application of the proposed system in clinical applications. In conclusion, the proposed dodecahedral PET system is potential for widespread applications in high-sensitivity, high-resolution PET imaging, to lower the injected dose. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Migraine classification using magnetic resonance imaging resting-state functional connectivity data.

PubMed

Chong, Catherine D; Gaw, Nathan; Fu, Yinlin; Li, Jing; Wu, Teresa; Schwedt, Todd J

2017-08-01

Background This study used machine-learning techniques to develop discriminative brain-connectivity biomarkers from resting-state functional magnetic resonance neuroimaging ( rs-fMRI) data that distinguish between individual migraine patients and healthy controls. Methods This study included 58 migraine patients (mean age = 36.3 years; SD = 11.5) and 50 healthy controls (mean age = 35.9 years; SD = 11.0). The functional connections of 33 seeded pain-related regions were used as input for a brain classification algorithm that tested the accuracy of determining whether an individual brain MRI belongs to someone with migraine or to a healthy control. Results The best classification accuracy using a 10-fold cross-validation method was 86.1%. Resting functional connectivity of the right middle temporal, posterior insula, middle cingulate, left ventromedial prefrontal and bilateral amygdala regions best discriminated the migraine brain from that of a healthy control. Migraineurs with longer disease durations were classified more accurately (>14 years; 96.7% accuracy) compared to migraineurs with shorter disease durations (≤14 years; 82.1% accuracy). Conclusions Classification of migraine using rs-fMRI provides insights into pain circuits that are altered in migraine and could potentially contribute to the development of a new, noninvasive migraine biomarker. Migraineurs with longer disease burden were classified more accurately than migraineurs with shorter disease burden, potentially indicating that disease duration leads to reorganization of brain circuitry.

Electrophysiological CNS-processes related to associative learning in humans.

PubMed

Christoffersen, Gert R J; Schachtman, Todd R

2016-01-01

The neurophysiology of human associative memory has been studied with electroencephalographic techniques since the 1930s. This research has revealed that different types of electrophysiological processes in the human brain can be modified by conditioning: sensory evoked potentials, sensory induced gamma-band activity, periods of frequency-specific waves (alpha and beta waves, the sensorimotor rhythm and the mu-rhythm) and slow cortical potentials. Conditioning of these processes has been studied in experiments that either use operant conditioning or repeated contingent pairings of conditioned and unconditioned stimuli (classical conditioning). In operant conditioning, the appearance of a specific brain process is paired with an external stimulus (neurofeedback) and the feedback enables subjects to obtain varying degrees of control of the CNS-process. Such acquired self-regulation of brain activity has found practical uses for instance in the amelioration of epileptic seizures, Autism Spectrum Disorders (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). It has also provided communicative means of assistance for tetraplegic patients through the use of brain computer interfaces. Both extra and intracortically recorded signals have been coupled with contingent external feedback. It is the aim for this review to summarize essential results on all types of electromagnetic brain processes that have been modified by classical or operant conditioning. The results are organized according to type of conditioned EEG-process, type of conditioning, and sensory modalities of the conditioning stimuli. Copyright © 2015 Elsevier B.V. All rights reserved.

Widespread Brain Areas Engaged during a Classical Auditory Streaming Task Revealed by Intracranial EEG

PubMed Central

Dykstra, Andrew R.; Halgren, Eric; Thesen, Thomas; Carlson, Chad E.; Doyle, Werner; Madsen, Joseph R.; Eskandar, Emad N.; Cash, Sydney S.

2011-01-01

The auditory system must constantly decompose the complex mixture of sound arriving at the ear into perceptually independent streams constituting accurate representations of individual sources in the acoustic environment. How the brain accomplishes this task is not well understood. The present study combined a classic behavioral paradigm with direct cortical recordings from neurosurgical patients with epilepsy in order to further describe the neural correlates of auditory streaming. Participants listened to sequences of pure tones alternating in frequency and indicated whether they heard one or two “streams.” The intracranial EEG was simultaneously recorded from sub-dural electrodes placed over temporal, frontal, and parietal cortex. Like healthy subjects, patients heard one stream when the frequency separation between tones was small and two when it was large. Robust evoked-potential correlates of frequency separation were observed over widespread brain areas. Waveform morphology was highly variable across individual electrode sites both within and across gross brain regions. Surprisingly, few evoked-potential correlates of perceptual organization were observed after controlling for physical stimulus differences. The results indicate that the cortical areas engaged during the streaming task are more complex and widespread than has been demonstrated by previous work, and that, by-and-large, correlates of bistability during streaming are probably located on a spatial scale not assessed – or in a brain area not examined – by the present study. PMID:21886615

Delivery of Small Interfering RNA to Inhibit Vascular Endothelial Growth Factor in Zebrafish Using Natural Brain Endothelia Cell-Secreted Exosome Nanovesicles for the Treatment of Brain Cancer.

PubMed

Yang, Tianzhi; Fogarty, Brittany; LaForge, Bret; Aziz, Salma; Pham, Thuy; Lai, Leanne; Bai, Shuhua

2017-03-01

Although small interfering RNA (siRNA) holds great therapeutic promise, its delivery to the disease site remains a paramount obstacle. In this study, we tested whether brain endothelial cell-derived exosomes could deliver siRNA across the blood-brain barrier (BBB) in zebrafish. Natural exosomes were isolated from brain endothelial bEND.3 cell culture media and vascular endothelial growth factor (VEGF) siRNA was loaded in exosomes with the assistance of a transfection reagent. While fluorescence-activated cell flow cytometry and immunocytochemistry staining studies indicated that wild-type exosomes significantly increased the uptake of fluorescence-labeled siRNA in the autologous brain endothelial cells, decreased fluorescence intensity was observed in the cells treated with the tetraspanin CD63 antibody-blocked exosome-delivered formulation (p < 0.05). In the transport study, exosomes also enhanced the permeability of rhodamine 123 in a co-cultured monolayer of brain endothelial bEND.3 cell and astrocyte. Inhibition at the expression of VEGF RNA and protein levels was observed in glioblastoma-astrocytoma U-87 MG cells treated with exosome-delivered siRNAs. Imaging results showed that exosome delivered more siRNAs across the BBB in Tg(fli1:GFP) zebrafish. In a xenotransplanted brain tumor model, exosome-delivered VEGF siRNAs decreased the fluorescence intensity of labeled cancer cells in the brain of zebrafish. Brain endothelial cell-derived exosomes could be potentially used as a natural carrier for the brain delivery of exogenous siRNA.

Enhancement of transport of curcumin to brain in mice by poly( n-butylcyanoacrylate) nanoparticle

NASA Astrophysics Data System (ADS)

Sun, Min; Gao, Yan; Guo, Chenyu; Cao, Fengliang; Song, Zhimei; Xi, Yanwei; Yu, Aihua; Li, Aiguo; Zhai, Guangxi

2010-10-01

Curcumin, a widely used coloring agent and spice in food, has a potential in blocking brain tumor formation and curing Alzheimer's disease. Due to the specific properties of blood-brain barrier (BBB), only traces of curcumin were transported across BBB. The aim of the present study was to design and characterize curcumin loaded polybutylcyanoacrylate nanoparticles (PBCN) coated with polysorbate 80, and to evaluate the effect of PBCN as a delivery system on carrying curcumin across BBB. Curcumin loaded nanoparticles were prepared by an anionic polymerization method, and they presented in a core-shell spherical shape under transmission electron microscopy, with an average diameter of 152.0 nm. The average drug loading was 21.1%. Physicochemical status of curcumin in the nanoparticles was confirmed with differential scanning colorimetry and Fourier transform infrared spectroscopy. The in vitro release behavior of drug from the nanoparticles was fitted to a double phase kinetics model. The studies of pharmacokinetic and bio-distribution to brain were conducted in mice after intravenous administration of the nanoparticle formulation at the dose of 5 mg/kg and curcumin solution at the dose of 10 mg/kg via the tail vein. The results showed that in plasma, the area under concentration-time curve (AUC0-∞) for curcumin loaded nanoparticles was greater than that for the control solution, moreover, the mean residence time of curcumin loaded nanoparticles was 14-fold that of the control solution. In brain, AUC0-∞ for curcumin loaded nanoparticles was 2.53-fold that for the control solution. In conclusion, the present study demonstrated that PBCN could enhance the transport of curcumin to brain and have a potential as a delivery system to cross the BBB.

Structural Imaging Measures of Brain Aging

PubMed Central

Lockhart, Samuel N.

2014-01-01

During the course of normal aging, biological changes occur in the brain that are associated with changes in cognitive ability. This review presents data from neuroimaging studies of primarily “normal” or healthy brain aging. As such, we focus on research in unimpaired or nondemented older adults, but also include findings from lifespan studies that include younger and middle aged individuals as well as from populations with prodromal or clinically symptomatic disease such as cerebrovascular or Alzheimer’s disease. This review predominantly addresses structural MRI biomarkers, such as volumetric or thickness measures from anatomical images, and measures of white matter injury and integrity respectively from FLAIR or DTI, and includes complementary data from PET and cognitive or clinical testing as appropriate. The findings reveal highly consistent age-related differences in brain structure, particularly frontal lobe and medial temporal regions that are also accompanied by age-related differences in frontal and medial temporal lobe mediated cognitive abilities. Newer findings also suggest that degeneration of specific white matter tracts such as those passing through the genu and splenium of the corpus callosum may also be related to age-related differences in cognitive performance. Interpretation of these findings, however, must be tempered by the fact that comorbid diseases such as cerebrovascular and Alzheimer’s disease also increase in prevalence with advancing age. As such, this review discusses challenges related to interpretation of current theories of cognitive aging in light of the common occurrence of these later-life diseases. Understanding the differences between “Normal” and “Healthy” brain aging and identifying potential modifiable risk factors for brain aging is critical to inform potential treatments to stall or reverse the effects of brain aging and possibly extend cognitive health for our aging society. PMID:25146995

Structural imaging measures of brain aging.

PubMed

Lockhart, Samuel N; DeCarli, Charles

2014-09-01

During the course of normal aging, biological changes occur in the brain that are associated with changes in cognitive ability. This review presents data from neuroimaging studies of primarily "normal" or healthy brain aging. As such, we focus on research in unimpaired or nondemented older adults, but also include findings from lifespan studies that include younger and middle aged individuals as well as from populations with prodromal or clinically symptomatic disease such as cerebrovascular or Alzheimer's disease. This review predominantly addresses structural MRI biomarkers, such as volumetric or thickness measures from anatomical images, and measures of white matter injury and integrity respectively from FLAIR or DTI, and includes complementary data from PET and cognitive or clinical testing as appropriate. The findings reveal highly consistent age-related differences in brain structure, particularly frontal lobe and medial temporal regions that are also accompanied by age-related differences in frontal and medial temporal lobe mediated cognitive abilities. Newer findings also suggest that degeneration of specific white matter tracts such as those passing through the genu and splenium of the corpus callosum may also be related to age-related differences in cognitive performance. Interpretation of these findings, however, must be tempered by the fact that comorbid diseases such as cerebrovascular and Alzheimer's disease also increase in prevalence with advancing age. As such, this review discusses challenges related to interpretation of current theories of cognitive aging in light of the common occurrence of these later-life diseases. Understanding the differences between "Normal" and "Healthy" brain aging and identifying potential modifiable risk factors for brain aging is critical to inform potential treatments to stall or reverse the effects of brain aging and possibly extend cognitive health for our aging society.

Effects of Mild Cognitive Impairment on the Event-Related Brain Potential Components Elicited in Executive Control Tasks.

PubMed

Zurrón, Montserrat; Lindín, Mónica; Cespón, Jesús; Cid-Fernández, Susana; Galdo-Álvarez, Santiago; Ramos-Goicoa, Marta; Díaz, Fernando

2018-01-01

We summarize here the findings of several studies in which we analyzed the event-related brain potentials (ERPs) elicited in participants with mild cognitive impairment (MCI) and in healthy controls during performance of executive tasks. The objective of these studies was to investigate the neural functioning associated with executive processes in MCI. With this aim, we recorded the brain electrical activity generated in response to stimuli in three executive control tasks (Stroop, Simon, and Go/NoGo) adapted for use with the ERP technique. We found that the latencies of the ERP components associated with the evaluation and categorization of the stimuli were longer in participants with amnestic MCI than in the paired controls, particularly those with multiple-domain amnestic MCI, and that the allocation of neural resources for attending to the stimuli was weaker in participants with amnestic MCI. The MCI participants also showed deficient functioning of the response selection and preparation processes demanded by each task.

Effects of Mild Cognitive Impairment on the Event-Related Brain Potential Components Elicited in Executive Control Tasks

PubMed Central

Zurrón, Montserrat; Lindín, Mónica; Cespón, Jesús; Cid-Fernández, Susana; Galdo-Álvarez, Santiago; Ramos-Goicoa, Marta; Díaz, Fernando

2018-01-01

We summarize here the findings of several studies in which we analyzed the event-related brain potentials (ERPs) elicited in participants with mild cognitive impairment (MCI) and in healthy controls during performance of executive tasks. The objective of these studies was to investigate the neural functioning associated with executive processes in MCI. With this aim, we recorded the brain electrical activity generated in response to stimuli in three executive control tasks (Stroop, Simon, and Go/NoGo) adapted for use with the ERP technique. We found that the latencies of the ERP components associated with the evaluation and categorization of the stimuli were longer in participants with amnestic MCI than in the paired controls, particularly those with multiple-domain amnestic MCI, and that the allocation of neural resources for attending to the stimuli was weaker in participants with amnestic MCI. The MCI participants also showed deficient functioning of the response selection and preparation processes demanded by each task.

Selective uptake of multi-walled carbon nanotubes by tumor macrophages in a murine glioma model.

PubMed

VanHandel, Michelle; Alizadeh, Darya; Zhang, Leying; Kateb, Babak; Bronikowski, Michael; Manohara, Harish; Badie, Behnam

2009-03-31

Carbon nantotubes (CNTs) are emerging as a new family of nanovectors for drug and gene delivery into biological systems. To evaluate potential application of this technology for brain tumor therapy, we studied uptake and toxicity of multi-walled CNTs (MWCNTs) in the GL261 murine intracranial glioma model. Within 24 h of a single intratumoral injection of labeled MWCNTs (5 microg), nearly 10-20% of total cells demonstrated CNT internalization. Most CNT uptake, however, occurred by tumor-associated macrophages (MP), which accounted for most (75%) MWCNT-positive cells. Within 24 h of injection, nearly 30% of tumor MP became MWCNT-positive. Despite a transient increase in inflammatory cell infiltration into both normal and tumor-bearing brains following MWCNT injection, no significant toxicity was noted in mice, and minor changes in tumor cytokine expression were observed. This study suggests that MWCNTs could potentially be used as a novel and non-toxic vehicle for targeting MP in brain tumors.

Clinical trial perspective for adult and juvenile Huntington's disease using genetically-engineered mesenchymal stem cells

PubMed Central

Deng, Peter; Torrest, Audrey; Pollock, Kari; Dahlenburg, Heather; Annett, Geralyn; Nolta, Jan A.; Fink, Kyle D.

2016-01-01

Progress to date from our group and others indicate that using genetically-engineered mesenchymal stem cells (MSC) to secrete brain-derived neurotrophic factor (BDNF) supports our plan to submit an Investigational New Drug application to the Food and Drug Administration for the future planned Phase 1 safety and tolerability trial of MSC/BDNF in patients with Huntington's disease (HD). There are also potential applications of this approach beyond HD. Our biological delivery system for BDNF sets the precedent for adult stem cell therapy in the brain and could potentially be modified for other neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), spinocerebellar ataxia (SCA), Alzheimer's disease, and some forms of Parkinson's disease. The MSC/BDNF product could also be considered for studies of regeneration in traumatic brain injury, spinal cord and peripheral nerve injury. This work also provides a platform for our future gene editing studies, since we will again use MSCs to deliver the needed molecules into the central nervous system. PMID:27335539

Neuronal chronometry of target detection: fusion of hemodynamic and event-related potential data.

PubMed

Calhoun, V D; Adali, T; Pearlson, G D; Kiehl, K A

2006-04-01

Event-related potential (ERP) studies of the brain's response to infrequent, target (oddball) stimuli elicit a sequence of physiological events, the most prominent and well studied being a complex, the P300 (or P3) peaking approximately 300 ms post-stimulus for simple stimuli and slightly later for more complex stimuli. Localization of the neural generators of the human oddball response remains challenging due to the lack of a single imaging technique with good spatial and temporal resolution. Here, we use independent component analyses to fuse ERP and fMRI modalities in order to examine the dynamics of the auditory oddball response with high spatiotemporal resolution across the entire brain. Initial activations in auditory and motor planning regions are followed by auditory association cortex and motor execution regions. The P3 response is associated with brainstem, temporal lobe, and medial frontal activity and finally a late temporal lobe "evaluative" response. We show that fusing imaging modalities with different advantages can provide new information about the brain.

Development of magneto-plasmonic nanoparticles for multimodal image-guided therapy to the brain.

PubMed

Tomitaka, Asahi; Arami, Hamed; Raymond, Andrea; Yndart, Adriana; Kaushik, Ajeet; Jayant, Rahul Dev; Takemura, Yasushi; Cai, Yong; Toborek, Michal; Nair, Madhavan

2017-01-05

Magneto-plasmonic nanoparticles are one of the emerging multi-functional materials in the field of nanomedicine. Their potential for targeting and multi-modal imaging is highly attractive. In this study, magnetic core/gold shell (MNP@Au) magneto-plasmonic nanoparticles were synthesized by citrate reduction of Au ions on magnetic nanoparticle seeds. Hydrodynamic size and optical properties of magneto-plasmonic nanoparticles synthesized with the variation of Au ions and reducing agent concentrations were evaluated. The synthesized magneto-plasmonic nanoparticles exhibited superparamagnetic properties, and their magnetic properties contributed to the concentration-dependent contrast in magnetic resonance imaging (MRI). The imaging contrast from the gold shell part of the magneto-plasmonic nanoparticles was also confirmed by X-ray computed tomography (CT). The transmigration study of the magneto-plasmonic nanoparticles using an in vitro blood-brain barrier (BBB) model proved enhanced transmigration efficiency without disrupting the integrity of the BBB, and showed potential to be used for brain diseases and neurological disorders.

Brain connectivity study of joint attention using frequency-domain optical imaging technique

NASA Astrophysics Data System (ADS)

Chaudhary, Ujwal; Zhu, Banghe; Godavarty, Anuradha

2010-02-01

Autism is a socio-communication brain development disorder. It is marked by degeneration in the ability to respond to joint attention skill task, from as early as 12 to 18 months of age. This trait is used to distinguish autistic from nonautistic populations. In this study, diffuse optical imaging is being used to study brain connectivity for the first time in response to joint attention experience in normal adults. The prefrontal region of the brain was non-invasively imaged using a frequency-domain based optical imager. The imaging studies were performed on 11 normal right-handed adults and optical measurements were acquired in response to joint-attention based video clips. While the intensity-based optical data provides information about the hemodynamic response of the underlying neural process, the time-dependent phase-based optical data has the potential to explicate the directional information on the activation of the brain. Thus brain connectivity studies are performed by computing covariance/correlations between spatial units using this frequency-domain based optical measurements. The preliminary results indicate that the extent of synchrony and directional variation in the pattern of activation varies in the left and right frontal cortex. The results have significant implication for research in neural pathways associated with autism that can be mapped using diffuse optical imaging tools in the future.

A Whole Methylome CpG-SNP Association Study of Psychosis in Blood and Brain Tissue.

PubMed

van den Oord, Edwin J C G; Clark, Shaunna L; Xie, Lin Ying; Shabalin, Andrey A; Dozmorov, Mikhail G; Kumar, Gaurav; Vladimirov, Vladimir I; Magnusson, Patrik K E; Aberg, Karolina A

2016-07-01

Mutated CpG sites (CpG-SNPs) are potential hotspots for human diseases because in addition to the sequence variation they may show individual differences in DNA methylation. We performed methylome-wide association studies (MWAS) to test whether methylation differences at those sites were associated with schizophrenia. We assayed all common CpG-SNPs with methyl-CpG binding domain protein-enriched genome sequencing (MBD-seq) using DNA extracted from 1408 blood samples and 66 postmortem brain samples (BA10) of schizophrenia cases and controls. Seven CpG-SNPs passed our FDR threshold of 0.1 in the blood MWAS. Of the CpG-SNPs methylated in brain, 94% were also methylated in blood. This significantly exceeded the 46.2% overlap expected by chance (P-value < 1.0×10(-8)) and justified replicating findings from blood in brain tissue. CpG-SNP rs3796293 in IL1RAP replicated (P-value = .003) with the same direction of effects. This site was further validated through targeted bisulfite pyrosequencing in 736 independent case-control blood samples (P-value < 9.5×10(-4)). Our top result in the brain MWAS (P-value = 8.8×10(-7)) was CpG-SNP rs16872141 located in the potential promoter of ENC1. Overall, our results suggested that CpG-SNP methylation may reflect effects of environmental insults and can provide biomarkers in blood that could potentially improve disease management. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Role of the endocannabinoid system in brain functions relevant for schizophrenia: an overview of human challenge studies with cannabis or ∆9-tetrahydrocannabinol (THC).

PubMed

Bossong, Matthijs G; Jansma, J Martijn; Bhattacharyya, Sagnik; Ramsey, Nick F

2014-07-03

Accumulating evidence suggests involvement of the endocannabinoid system in the pathophysiology of schizophrenia, which signifies a potential application for this system in the treatment of this disorder. However, before new research can focus on potential treatments that work by manipulating the endocannabinoid system, it needs to be elucidated how this system is involved in symptoms of schizophrenia. Here we review human studies that investigated acute effects of cannabis or ∆9-tetrahydrocannabinol (THC) on brain functions that are implicated in schizophrenia. Results suggest that the impact of THC administration depends on the difficulty of the task performed. Impaired performance of cognitive paradigms is reported on more challenging tasks, which is associated with both activity deficits in temporal and prefrontal areas and a failure to deactivate regions of the default mode network. Comparable reductions in prefrontal activity and impairments in deactivation of the default mode network are seen in patients during performance of cognitive paradigms. Normal performance levels after THC administration demonstrated for less demanding tasks are shown to be related to either increased neural effort in task-specific regions ('neurophysiological inefficiency'), or recruitment of alternative brain areas, which suggests a change in strategy to meet cognitive demands. Particularly a pattern of performance and brain activity corresponding with an inefficient working memory system is consistently demonstrated in patients. These similarities in brain function between intoxicated healthy volunteers and schizophrenia patients provide an argument for a role of the endocannabinoid system in symptoms of schizophrenia, and further emphasize this system as a potential novel target for treatment of these symptoms. Copyright © 2014 Elsevier Inc. All rights reserved.

Persistent cognitive and dopamine transporter deficits in abstinent methamphetamine users.

PubMed

McCann, Una D; Kuwabara, Hiroto; Kumar, Anil; Palermo, Michael; Abbey, Rubyna; Brasic, James; Ye, Weiguo; Alexander, Mohab; Dannals, Robert F; Wong, Dean F; Ricaurte, George A

2008-02-01

Studies in abstinent methamphetamine (METH) users have demonstrated reductions in brain dopamine transporter (DAT) binding potential (BP), as well as cognitive and motor deficits, but it is not yet clear whether cognitive deficits and brain DAT reductions fully reverse with sustained abstinence, or whether behavioral deficits in METH users are related to dopamine (DA) deficits. This study was conducted to further investigate potential persistent psychomotor deficits secondary to METH abuse, and their relationship to brain DAT availability, as measured using quantitative PET methods with [(11)C]WIN 35428. Twenty-two abstinent METH users and 17 healthy non-METH using controls underwent psychometric testing to test the hypothesis that METH users would demonstrate selective deficits in neuropsychiatric domains known to involve DA neurons (e.g., working memory, executive function, motor function). A subset of subjects also underwent PET scanning with [(11)C]WIN 35428. METH users were found to have modest deficits in short-term memory, executive function, and manual dexterity. Exploratory correlational analyses revealed that deficits in memory, but not those in executive or motor function, were associated with decreases in striatal DAT BP. These results suggest a possible relationship between DAT BP and memory deficits in abstinent METH users, and lend support to the notion that METH produces lasting effects on central DA neurons in humans. As METH can also produce toxic effects on serotonin (5-HT) neurons, further study is needed to address the potential role of brain 5-HT depletion in cognitive deficits in abstinent METH users. (c) 2007 Wiley-Liss, Inc.

Drug delivery in overcoming the blood–brain barrier: role of nasal mucosal grafting

PubMed Central

Marianecci, Carlotta; Rinaldi, Federica; Hanieh, Patrizia Nadia; Di Marzio, Luisa; Paolino, Donatella; Carafa, Maria

2017-01-01

The blood–brain barrier (BBB) plays a fundamental role in protecting and maintaining the homeostasis of the brain. For this reason, drug delivery to the brain is much more difficult than that to other compartments of the body. In order to bypass or cross the BBB, many strategies have been developed: invasive techniques, such as temporary disruption of the BBB or direct intraventricular and intracerebral administration of the drug, as well as noninvasive techniques. Preliminary results, reported in the large number of studies on the potential strategies for brain delivery, are encouraging, but it is far too early to draw any conclusion about the actual use of these therapeutic approaches. Among the most recent, but still pioneering, approaches related to the nasal mucosa properties, the permeabilization of the BBB via nasal mucosal engrafting can offer new potential opportunities. It should be emphasized that this surgical procedure is quite invasive, but the implication for patient outcome needs to be compared to the gold standard of direct intracranial injection, and evaluated whilst keeping in mind that central nervous system diseases and lysosomal storage diseases are chronic and severely debilitating and that up to now no therapy seems to be completely successful. PMID:28184152

Reducing proactive aggression through non-invasive brain stimulation

PubMed Central

Schuhmann, Teresa; Lobbestael, Jill; Arntz, Arnoud; Brugman, Suzanne; Sack, Alexander T.

2015-01-01

Aggressive behavior poses a threat to human collaboration and social safety. It is of utmost importance to identify the functional mechanisms underlying aggression and to develop potential interventions capable of reducing dysfunctional aggressive behavior already at a brain level. We here experimentally shifted fronto-cortical asymmetry to manipulate the underlying motivational emotional states in both male and female participants while assessing the behavioral effects on proactive and reactive aggression. Thirty-two healthy volunteers received either anodal transcranial direct current stimulation to increase neural activity within right dorsolateral prefrontal cortex, or sham stimulation. Aggressive behavior was measured with the Taylor Aggression Paradigm. We revealed a general gender effect, showing that men displayed more behavioral aggression than women. After the induction of right fronto-hemispheric dominance, proactive aggression was reduced in men. This study demonstrates that non-invasive brain stimulation can reduce aggression in men. This is a relevant and promising step to better understand how cortical brain states connect to impulsive actions and to examine the causal role of the prefrontal cortex in aggression. Ultimately, such findings could help to examine whether the brain can be a direct target for potential supportive interventions in clinical settings dealing with overly aggressive patients and/or violent offenders. PMID:25680991

Liver procurement from a brain-dead kidney transplant recipient--a case report.

PubMed

Romatowska, Edyta; Woderska, Aleksandra; Kusza, Krzysztof; Słupski, Maciej; Neumann, Małgorzata

2012-01-01

The shortage of organ donors has led to new strategies to increase the availability of allografts for transplantation, such as organ procurement from brain-dead organ transplant recipients. We present the case of a 26 year-old male brain-dead liver donor who had been a kidney transplant recipient six years previously. The liver donor described in this report, as the first in Poland, has paved a new, although as yet narrow, way in the field of organ donation. This is also the first case described in the medical literature of liver recovery from a brain-dead kidney transplant recipient on an immunosuppressive regimen with three immunosuppressive agents. Although transplant recipients represent an uncommon group of deceased organ donors, it is probable that situations when they may be considered as potential organ donors will occur more often. Therefore, although specific criteria for organ donors exist, each reported potential donor should be considered individually, and brain-dead solid organ recipients should not be excluded a priori as organ donors; both their native and allografted organs may be recovered and successfully transplanted. In this study, we also review the current state of knowledge on the reuse of organs.

Immunohistochemical Demonstration of Specific Antigens in the Human Brain Fixed in Zinc-ethanol-Formaldehyde

PubMed Central

Korzhevskii, D.E.; Sukhorukova, E.G.; Kirik, O.V.; Grigorev, I.P.

2015-01-01

Tissue fixation is critical for immunohistochemistry. Recently, we developed a zinc-ethanol-formalin fixative (ZEF), and the present study was aimed to assess the applicability of the ZEF for the human brain histology and immunohistochemistry and to evaluate the detectability of different antigens in the human brain fixed with ZEF. In total, 11 antigens were tested, including NeuN, neuron-specific enolase, GFAP, Iba-1, calbindin, calretinin, choline acetyltransferase, glutamic acid decarboxylase (GAD65), tyrosine hydroxylase, synaptophysin, and α-tubulin. The obtained data show that: i) the ZEF has potential for use in general histological practice, where detailed characterization of human brain morphology is needed; ii) the antigens tested are well-preserved in the human brain specimens fixed in the ZEF. PMID:26428887

Targeting receptor-mediated transport for delivery of biologics across the blood-brain barrier.

PubMed

Lajoie, Jason M; Shusta, Eric V

2015-01-01

Biologics are an emerging class of medicines with substantial promise to treat neurological disorders such as Alzheimer's disease, stroke, and multiple sclerosis. However, the blood-brain barrier (BBB) presents a formidable obstacle that appreciably limits brain uptake and hence the therapeutic potential of biologics following intravenous administration. One promising strategy for overcoming the BBB to deliver biologics is the targeting of endogenous receptor-mediated transport (RMT) systems that employ vesicular trafficking to transport ligands across the BBB endothelium. If a biologic is modified with an appropriate targeting ligand, it can gain improved access to the brain via RMT. Various RMT-targeting strategies have been developed over the past 20 years, and this review explores exciting recent advances, emphasizing studies that show brain targeting in vivo.

Affection of Fundamental Brain Activity By Using Sounds For Patients With Prosodic Disorders: A Pilot Study

NASA Astrophysics Data System (ADS)

Imai, Emiko; Katagiri, Yoshitada; Seki, Keiko; Kawamata, Toshio

2011-06-01

We present a neural model of the production of modulated speech streams in the brain, referred to as prosody, which indicates the limbic structure essential for producing prosody both linguistically and emotionally. This model suggests that activating the fundamental brain including monoamine neurons at the basal ganglia will potentially contribute to helping patients with prosodic disorders coming from functional defects of the fundamental brain to overcome their speech problem. To establish effective clinical treatment for such prosodic disorders, we examine how sounds affect the fundamental activity by using electroencephalographic measurements. Throughout examinations with various melodious sounds, we found that some melodies with lilting rhythms successfully give rise to the fast alpha rhythms at the electroencephalogram which reflect the fundamental brain activity without any negative feelings.

How heart rate variability affects emotion regulation brain networks.

PubMed

Mather, Mara; Thayer, Julian

2018-02-01

Individuals with high heart rate variability tend to have better emotional well-being than those with low heart rate variability, but the mechanisms of this association are not yet clear. In this paper, we propose the novel hypothesis that by inducing oscillatory activity in the brain, high amplitude oscillations in heart rate enhance functional connectivity in brain networks associated with emotion regulation. Recent studies using daily biofeedback sessions to increase the amplitude of heart rate oscillations suggest that high amplitude physiological oscillations have a causal impact on emotional well-being. Because blood flow timing helps determine brain network structure and function, slow oscillations in heart rate have the potential to strengthen brain network dynamics, especially in medial prefrontal regulatory regions that are particularly sensitive to physiological oscillations.

The gravitational field and brain function.

PubMed

Mei, L; Zhou, C D; Lan, J Q; Wang, Z G; Wu, W C; Xue, X M

1983-01-01

The frontal cortex is recognized as the highest adaptive control center of the human brain. The principle of the "frontalization" of human brain function offers new possibilities for brain research in space. There is evolutionary and experimental evidence indicating the validity of the principle, including it's role in nervous response to gravitational stimulation. The gravitational field is considered here as one of the more constant and comprehensive factors acting on brain evolution, which has undergone some successive crucial steps: "encephalization", "corticalization", "lateralization" and "frontalization". The dominating effects of electrical responses from the frontal cortex have been discovered 1) in experiments under gravitational stimulus; and 2) in processes potentially relating to gravitational adaptation, such as memory and learning, sensory information processing, motor programing, and brain state control. A brain research experiment during space flight is suggested to test the role of the frontal cortex in space adaptation and it's potentiality in brain control.

Melanoma Brain Metastasis: Mechanisms, Models, and Medicine

PubMed Central

Kircher, David A.; Silvis, Mark R.; Cho, Joseph H.; Holmen, Sheri L.

2016-01-01

The development of brain metastases in patients with advanced stage melanoma is common, but the molecular mechanisms responsible for their development are poorly understood. Melanoma brain metastases cause significant morbidity and mortality and confer a poor prognosis; traditional therapies including whole brain radiation, stereotactic radiotherapy, or chemotherapy yield only modest increases in overall survival (OS) for these patients. While recently approved therapies have significantly improved OS in melanoma patients, only a small number of studies have investigated their efficacy in patients with brain metastases. Preliminary data suggest that some responses have been observed in intracranial lesions, which has sparked new clinical trials designed to evaluate the efficacy in melanoma patients with brain metastases. Simultaneously, recent advances in our understanding of the mechanisms of melanoma cell dissemination to the brain have revealed novel and potentially therapeutic targets. In this review, we provide an overview of newly discovered mechanisms of melanoma spread to the brain, discuss preclinical models that are being used to further our understanding of this deadly disease and provide an update of the current clinical trials for melanoma patients with brain metastases. PMID:27598148

Injury-Related Production of Cysteinyl Leukotrienes Contributes to Brain Damage following Experimental Traumatic Brain Injury

PubMed Central

Farias, Santiago; Frey, Lauren C.; Murphy, Robert C.

2009-01-01

Abstract The leukotrienes belong to a family of biologically active lipids derived from arachidonate that are often involved in inflammatory responses. In the central nervous system, a group of leukotrienes, known as the cysteinyl leukotrienes, is generated in brain tissue in response to a variety of acute brain injuries. Although the exact clinical significance of this excess production remains unclear, the cysteinyl leukotrienes may contribute to injury-related disruption of the brain-blood barrier and exacerbate secondary injury processes. In the present study, the formation and role of cysteinyl leukotrienes was explored in the fluid percussion injury model of traumatic brain injury in rats. The results showed that levels of the cysteinyl leukotrienes were elevated after fluid percussion injury with a maximal formation 1 hour after the injury. Neutrophils contributed to cysteinyl leukotriene formation in the injured brain hemisphere, potentially through a transcellular biosynthetic mechanism. Furthermore, pharmacological reduction of cysteinyl leukotriene formation after the injury, using MK-886, resulted in reduction of brain lesion volumes, suggesting that the cysteinyl leukotrienes play an important role in traumatic brain injury. PMID:19886806

Functional MRI Preprocessing in Lesioned Brains: Manual Versus Automated Region of Interest Analysis

PubMed Central

Garrison, Kathleen A.; Rogalsky, Corianne; Sheng, Tong; Liu, Brent; Damasio, Hanna; Winstein, Carolee J.; Aziz-Zadeh, Lisa S.

2015-01-01

Functional magnetic resonance imaging (fMRI) has significant potential in the study and treatment of neurological disorders and stroke. Region of interest (ROI) analysis in such studies allows for testing of strong a priori clinical hypotheses with improved statistical power. A commonly used automated approach to ROI analysis is to spatially normalize each participant’s structural brain image to a template brain image and define ROIs using an atlas. However, in studies of individuals with structural brain lesions, such as stroke, the gold standard approach may be to manually hand-draw ROIs on each participant’s non-normalized structural brain image. Automated approaches to ROI analysis are faster and more standardized, yet are susceptible to preprocessing error (e.g., normalization error) that can be greater in lesioned brains. The manual approach to ROI analysis has high demand for time and expertise, but may provide a more accurate estimate of brain response. In this study, commonly used automated and manual approaches to ROI analysis were directly compared by reanalyzing data from a previously published hypothesis-driven cognitive fMRI study, involving individuals with stroke. The ROI evaluated is the pars opercularis of the inferior frontal gyrus. Significant differences were identified in task-related effect size and percent-activated voxels in this ROI between the automated and manual approaches to ROI analysis. Task interactions, however, were consistent across ROI analysis approaches. These findings support the use of automated approaches to ROI analysis in studies of lesioned brains, provided they employ a task interaction design. PMID:26441816

Peripheral administration of the soluble TNF inhibitor XPro1595 modifies brain immune cell profiles, decreases beta-amyloid plaque load, and rescues impaired long-term potentiation in 5xFAD mice.

PubMed

MacPherson, Kathryn P; Sompol, Pradoldej; Kannarkat, George T; Chang, Jianjun; Sniffen, Lindsey; Wildner, Mary E; Norris, Christopher M; Tansey, Malú G

2017-06-01

Clinical and animal model studies have implicated inflammation and peripheral immune cell responses in the pathophysiology of Alzheimer's disease (AD). Peripheral immune cells including T cells circulate in the cerebrospinal fluid (CSF) of healthy adults and are found in the brains of AD patients and AD rodent models. Blocking entry of peripheral macrophages into the CNS was reported to increase amyloid burden in an AD mouse model. To assess inflammation in the 5xFAD (Tg) mouse model, we first quantified central and immune cell profiles in the deep cervical lymph nodes and spleen. In the brains of Tg mice, activated (MHCII + , CD45 high , and Ly6C high ) myeloid-derived CD11b + immune cells are decreased while CD3 + T cells are increased as a function of age relative to non-Tg mice. These immunological changes along with evidence of increased mRNA levels for several cytokines suggest that immune regulation and trafficking patterns are altered in Tg mice. Levels of soluble Tumor Necrosis Factor (sTNF) modulate blood-brain barrier (BBB) permeability and are increased in CSF and brain parenchyma post-mortem in AD subjects and Tg mice. We report here that in vivo peripheral administration of XPro1595, a novel biologic that sequesters sTNF into inactive heterotrimers, reduced the age-dependent increase in activated immune cells in Tg mice, while decreasing the overall number of CD4 + T cells. In addition, XPro1595 treatment in vivo rescued impaired long-term potentiation (LTP) measured in brain slices in association with decreased Aβ plaques in the subiculum. Selective targeting of sTNF may modulate brain immune cell infiltration, and prevent or delay neuronal dysfunction in AD. Immune cells and cytokines perform specialized functions inside and outside the brain to maintain optimal brain health; but the extent to which their activities change in response to neuronal dysfunction and degeneration is not well understood. Our findings indicate that neutralization of sTNF reduced the age-dependent increase in activated immune cells in Tg mice, while decreasing the overall number of CD4 + T cells. In addition, impaired long-term potentiation (LTP) was rescued by XPro1595 in association with decreased hippocampal Aβ plaques. Selective targeting of sTNF holds translational potential to modulate brain immune cell infiltration, dampen neuroinflammation, and prevent or delay neuronal dysfunction in AD. Copyright © 2017 Elsevier Inc. All rights reserved.

A technical guide to tDCS, and related non-invasive brain stimulation tools

PubMed Central

Woods, AJ; Antal, A; Bikson, M; Boggio, PS; Brunoni, AR; Celnik, P; Cohen, LG; Fregni, F; Herrmann, CS; Kappenman, ES; Knotkova, H; Liebetanz, D; Miniussi, C; Miranda, PC; Paulus, W; Priori, A; Reato, D; Stagg, C; Wenderoth, N; Nitsche, MA

2015-01-01

Transcranial electrical stimulation (tES), including transcranial direct and alternating current stimulation (tDCS, tACS) are non-invasive brain stimulation techniques increasingly used for modulation of central nervous system excitability in humans. Here we address methodological issues required for tES application. This review covers technical aspects of tES, as well as applications like exploration of brain physiology, modelling approaches, tES in cognitive neurosciences, and interventional approaches. It aims to help the reader to appropriately design and conduct studies involving these brain stimulation techniques, understand limitations and avoid shortcomings, which might hamper the scientific rigor and potential applications in the clinical domain. PMID:26652115

Premorbid personality characteristics and attachment style moderate the effect of injury severity on occupational outcome in traumatic brain injury: another aspect of reserve.

PubMed

Sela-Kaufman, Michal; Rassovsky, Yuri; Agranov, Eugenia; Levi, Yifat; Vakil, Eli

2013-01-01

The concept of "reserve" has been proposed to account for the mismatch between brain pathology and its clinical expression. Prior efforts to characterize this concept focused mostly on brain or cognitive reserve measures. The present study was a preliminary attempt to evaluate premorbid personality and emotional aspects as potential moderators in moderate-to-severe traumatic brain injury. Using structural equation modeling and multiple regression analyses, we found that premorbid personality characteristics provided the most robust moderator of injury severity on occupational outcome. Findings offer preliminary support for premorbid personality features as another relevant reserve construct in predicting outcome in this population.

Focused Ultrasound-Induced Blood–Brain Barrier Opening to Enhance Temozolomide Delivery for Glioblastoma Treatment: A Preclinical Study

PubMed Central

Wei, Kuo-Chen; Chu, Po-Chun; Wang, Hay-Yan Jack; Huang, Chiung-Yin; Chen, Pin-Yuan; Tsai, Hong-Chieh; Lu, Yu-Jen; Lee, Pei-Yun; Tseng, I-Chou; Feng, Li-Ying; Hsu, Peng-Wei; Yen, Tzu-Chen; Liu, Hao-Li

2013-01-01

The purpose of this study is to assess the preclinical therapeutic efficacy of magnetic resonance imaging (MRI)-monitored focused ultrasound (FUS)-induced blood-brain barrier (BBB) disruption to enhance Temozolomide (TMZ) delivery for improving Glioblastoma Multiforme (GBM) treatment. MRI-monitored FUS with microbubbles was used to transcranially disrupt the BBB in brains of Fisher rats implanted with 9L glioma cells. FUS-BBB opening was spectrophotometrically determined by leakage of dyes into the brain, and TMZ was quantitated in cerebrospinal fluid (CSF) and plasma by LC-MS\\MS. The effects of treatment on tumor progression (by MRI), animal survival and brain tissue histology were investigated. Results demonstrated that FUS-BBB opening increased the local accumulation of dyes in brain parenchyma by 3.8-/2.1-fold in normal/tumor tissues. Compared to TMZ alone, combined FUS treatment increased the TMZ CSF/plasma ratio from 22.7% to 38.6%, reduced the 7-day tumor progression ratio from 24.03 to 5.06, and extended the median survival from 20 to 23 days. In conclusion, this study provided preclinical evidence that FUS BBB-opening increased the local concentration of TMZ to improve the control of tumor progression and animal survival, suggesting its clinical potential for improving current brain tumor treatment. PMID:23527068

Brain activation by music in patients in a vegetative or minimally conscious state following diffuse brain injury.

PubMed

Okumura, Yuka; Asano, Yoshitaka; Takenaka, Shunsuke; Fukuyama, Seisuke; Yonezawa, Shingo; Kasuya, Yukinori; Shinoda, Jun

2014-01-01

The aim of this study was to objectively evaluate the brain activity potential of patients with impaired consciousness in a chronic stage of diffuse brain injury (DBI) using functional MRI (fMRI) following music stimulation (MS). Two patients in a minimally conscious state (MCS) and five patients in a vegetative state (VS) due to severe DBI were enrolled along with 21 healthy adults. This study examined the brain regions activated by music and assessed topographical differences of the MS-activated brain among healthy adults and these patients. MS was shown to activate the bilateral superior temporal gyri (STG) of both healthy adults and patients in an MCS. In four of five patients in a VS, however, no significant activation in STG could be induced by the same MS. The remaining patient in a VS displayed the same MS-induced brain activation in STG as healthy adults and patients in an MCS and this patient's status also improved to an MCS 4 months after the study. The presence of STG activation by MS may predict a possible improvement of patients in a VS to MCS and fMRI employing MS may be a useful modality to objectively evaluate consciousness in these patients.

Efficacy of icotinib versus traditional chemotherapy as first-line treatment for preventing brain metastasis from advanced lung adenocarcinoma in patients with epidermal growth factor receptor-sensitive mutation.

PubMed

Zhao, Xiao; Zhu, Guangqin; Chen, Huoming; Yang, Ping; Li, Fang; Du, Nan

2016-01-01

This study aimed to investigate the potential use of icotinib as first-line treatment to prevent brain metastasis from advanced lung adenocarcinoma. This investigation was designed as a retrospective nonrandomized controlled study. Enrolled patients received either icotinib or traditional chemotherapy as their first-line treatment. The therapeutic efficacy was compared among patients with advanced. (stages IIIB and IV) lung adenocarcinoma with epidermal growth factor receptor (EGFR)-sensitive mutation. The primary endpoint was the cumulative incidence of brain metastasis, whereas, the secondary endpoint was overall survival(OS). Death without brain metastasis was considered a competitive risk to calculate the cumulative risk of brain metastasis. Survival analysis was conducted using the Kaplan-Meier method and statistical significance was determined using the log-rank test. The present study included 396 patients with 131 in the icotinib group and 265 in the chemotherapy group. Among those with EGFR-sensitive mutation, the cumulative risk of brain metastasis was lower in the icotinib group than in the chemotherapy group. However, no significant difference in OS was observed between the two groups. Icotinib can effectively reduce the incidence of brain metastasis and therefore improve prognosis in advanced lung adenocarcinoma patients with EGFR.sensitive mutation.

Efficacy of icotinib versus traditional chemotherapy as first-line treatment for preventing brain metastasis from advanced lung adenocarcinoma in patients with epidermal growth factor receptor-sensitive mutation.

PubMed

Zhao, Xiao; Zhu, Guangqin; Chen, Huoming; Yang, Ping; Li, Fang; Du, Nan

2014-11-01

This study aimed to investigate the potential use of icotinib as first-line treatment to prevent brain metastasis from advanced lung adenocarcinoma. This investigation was designed as a retrospective nonrandomized controlled study. Enrolled patients received either icotinib or traditional chemotherapy as their first-line treatment. The therapeutic efficacy was compared among patients with advanced (stages IIIB and IV) lung adenocarcinoma with epidermal growth factor receptor (EGFR)-sensitive mutation. The primary endpoint was the cumulative incidence of brain metastasis, whereas the secondary endpoint was overall survival (OS). Death without brain metastasis was considered a competitive risk to calculate the cumulative risk of brain metastasis. Survival analysis was conducted using the Kaplan-Meier method and statistical significance were determined using the log-rank test. The present study included 396 patients with 131 in the icotinib group and 265 in the chemotherapy group. Among those with EGFR-sensitive mutation, the cumulative risk of brain metastasis was lower in the icotinib group than in the chemotherapy group. However, no significant difference in OS was observed between the two groups. Icotinib can effectively reduce the incidence of brain metastasis and therefore improve prognosis in advanced lung adenocarcinoma patients with EGFR-sensitive mutation.

Potential effects of environmental contaminants on P450 aromatase activity and DNA damage in swallows from the Rio Grande and Somerville, Texas

USGS Publications Warehouse

Sitzlar, M.A.; Mora, M.A.; Fleming, J.G.W.; Bazer, F.W.; Bickham, J.W.; Matson, C.W.

2009-01-01

Cliff swallows (Petrochelidon pyrrhonota) and cave swallows (P. fulva) were sampled during the breeding season at several locations in the Rio Grande, Texas, to evaluate the potential effects of environmental contaminants on P450 aromatase activity in brain and gonads and DNA damage in blood cells. The tritiated water-release aromatase assay was used to measure aromatase activity and flow cytometry was used to measure DNA damage in nucleated blood cells. There were no significant differences in brain and gonadal aromatase activities or in estimates of DNA damage (HPCV values) among cave swallow colonies from the Lower Rio Grande Valley (LRGV) and Somerville. However, both brain and gonadal aromatase activities were significantly higher (P < 0.05) in male cliff swallows from Laredo than in those from Somerville. Also, DNA damage estimates were significantly higher (P < 0.05) in cliff swallows (males and females combined) from Laredo than in those from Somerville. Contaminants of current high use in the LRGV, such as atrazine, and some of the highly persistent organochlorines, such as toxaphene and DDE, could be potentially associated with modulation of aromatase activity in avian tissues. Previous studies have indicated possible DNA damage in cliff swallows. We did not observe any differences in aromatase activity or DNA damage in cave swallows that could be associated with contaminant exposure. Also, the differences in aromatase activity and DNA damage between male cliff swallows from Laredo and Somerville could not be explained by contaminants measured at each site in previous studies. Our study provides baseline information on brain and gonadal aromatase activity in swallows that could be useful in future studies. ?? 2008 Springer Science+Business Media, LLC.

Cognitive Priming and Cognitive Training: Immediate and Far Transfer to Academic Skills in Children.

PubMed

Wexler, Bruce E; Iseli, Markus; Leon, Seth; Zaggle, William; Rush, Cynthia; Goodman, Annette; Esat Imal, A; Bo, Emily

2016-09-12

Cognitive operations are supported by dynamically reconfiguring neural systems that integrate processing components widely distributed throughout the brain. The inter-neuronal connections that constitute these systems are powerfully shaped by environmental input. We evaluated the ability of computer-presented brain training games done in school to harness this neuroplastic potential and improve learning in an overall study sample of 583 second-grade children. Doing a 5-minute brain-training game immediately before math or reading curricular content games increased performance on the curricular content games. Doing three 20-minute brain training sessions per week for four months increased gains on school-administered math and reading achievement tests compared to control classes tested at the same times without intervening brain training. These results provide evidence of cognitive priming with immediate effects on learning, and longer-term brain training with far-transfer or generalized effects on academic achievement.

Cognitive Priming and Cognitive Training: Immediate and Far Transfer to Academic Skills in Children

PubMed Central

Wexler, Bruce E; Iseli, Markus; Leon, Seth; Zaggle, William; Rush, Cynthia; Goodman, Annette; Esat Imal, A.; Bo, Emily

2016-01-01

Cognitive operations are supported by dynamically reconfiguring neural systems that integrate processing components widely distributed throughout the brain. The inter-neuronal connections that constitute these systems are powerfully shaped by environmental input. We evaluated the ability of computer-presented brain training games done in school to harness this neuroplastic potential and improve learning in an overall study sample of 583 second-grade children. Doing a 5-minute brain-training game immediately before math or reading curricular content games increased performance on the curricular content games. Doing three 20-minute brain training sessions per week for four months increased gains on school-administered math and reading achievement tests compared to control classes tested at the same times without intervening brain training. These results provide evidence of cognitive priming with immediate effects on learning, and longer-term brain training with far-transfer or generalized effects on academic achievement. PMID:27615029

Optogenetic mapping of brain circuitry

NASA Astrophysics Data System (ADS)

Augustine, George J.; Berglund, Ken; Gill, Harin; Hoffmann, Carolin; Katarya, Malvika; Kim, Jinsook; Kudolo, John; Lee, Li M.; Lee, Molly; Lo, Daniel; Nakajima, Ryuichi; Park, Min Yoon; Tan, Gregory; Tang, Yanxia; Teo, Peggy; Tsuda, Sachiko; Wen, Lei; Yoon, Su-In

2012-10-01

Studies of the brain promise to be revolutionized by new experimental strategies that harness the combined power of optical techniques and genetics. We have mapped the circuitry of the mouse brain by using both optogenetic actuators that control neuronal activity and optogenetic sensors that detect neuronal activity. Using the light-activated cation channel, channelrhodopsin-2, to locally photostimulate neurons allows high-speed mapping of local and long-range circuitry. For example, with this approach we have mapped local circuits in the cerebral cortex, cerebellum and many other brain regions. Using the fluorescent sensor for chloride ions, Clomeleon, allows imaging of the spatial and temporal dimensions of inhibitory circuits in the brain. This approach allows imaging of both conventional "phasic" synaptic inhibition as well as unconventional "tonic" inhibition. The combined use of light to both control and monitor neural activity creates unprecedented opportunities to explore brain function, screen pharmaceutical agents, and potentially to use light to ameliorate psychiatric and neurological disorders.

Extracorporeal methods of blood glutamate scavenging: a novel therapeutic modality.

PubMed

Zhumadilov, Agzam; Boyko, Matthew; Gruenbaum, Shaun E; Brotfain, Evgeny; Bilotta, Federico; Zlotnik, Alexander

2015-05-01

Pathologically elevated glutamate concentrations in the brain's extracellular fluid are associated with several acute and chronic brain insults. Studies have demonstrated that by decreasing the concentration of glutamate in the blood, thereby increasing the concentration gradient between the brain and the blood, the rate of brain-to-blood glutamate efflux can be increased. Blood glutamate scavengers, pyruvate and oxaloacetate have shown great promise in providing neuroprotection in many animal models of acute brain insults. However, glutamate scavengers' potential systemic toxicity, side effects and pharmacokinetic properties may limit their use in clinical practice. In contrast, extracorporeal methods of blood glutamate reduction, in which glutamate is filtered from the blood and eliminated, may be an advantageous adjunct in treating acute brain insults. Here, we review the current evidence for the glutamate-lowering effects of hemodialysis, peritoneal dialysis and hemofiltration. The evidence reviewed here highlights the need for clinical trials.

[Moderate hypoglycemia in the preterm infant: is it relevant?].

PubMed

Wayenberg, J-L; Pardou, A

2008-02-01

Glucose monitoring and management of hypoglycaemia in preterm infants remain controversial. However, recent animal studies have shown that hypoglycaemia is associated to increased generation of reactive oxygen and nitrogen species, to inhibition of cellular maturation and to apoptosis in brain. Despite potential consequences of hypoglycaemia on brain development in preterm infants, only few studies are available on this topic. Available clinical studies on neurological development of hypoglycaemic preterm infants are not conclusive but suggest detrimental effect of repeated mild hypoglycaemia on brain development. Both experimental and clinical arguments are sufficient to mind to this problem with great awareness. Therefore, routine repeated measurements of blood glucose concentration are necessary and active intervention is proposed if glucose plasma level decreases below 2.5 mmol/l.

Statins as neuroprotectants: a comparative in vitro study of lipophilicity, blood-brain-barrier penetration, lowering of brain cholesterol, and decrease of neuron cell death.

PubMed

Sierra, Saleta; Ramos, Maria C; Molina, Pilar; Esteo, Cynthia; Vázquez, Jose Antonio; Burgos, Javier S

2011-01-01

There is growing evidence to support the hypothesis that statins may act as neuroprotectants in several neuropathological conditions, including Alzheimer's disease. The mechanisms for neuroprotection are only partially understood, however, and pleiotropic phenomena could be involved. We have made a comparative study of 9 statins (lovastatin, mevastatin, pravastatin, simvastatin, cerivastatin, atorvastatin, fluvastatin, pitavastatin, and rosuvastatin), analyzing several parameters that could be related to neuroprotection, such as chemical structure, lipophilicity, potential blood-brain-barrier penetration (BBB), 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibition, cholesterol modulation in neurons, glia, and human hepatocyte cell lines, and protection against neurodegeneration caused by tau hyperphosphorylation induced by okadaic acid. Our results indicate that monacolin J derivatives (natural and semi-synthetic statins) are the best candidates for the prevention of neurodegenerative conditions due to their higher potential BBB penetration capacity, cholesterol lowering effect on neurons with a satisfactory safety profile, and in vitro protection against cell death caused by okadaic acid in culture. Among the nine statins studied, simvastatin presented the best characteristics for preventing neurodegenerative conditions.

Will My Soul Go to Heaven If They Take My Brain? Beliefs and Worries About Brain Donation Among Four Ethnic Groups.

PubMed

Boise, Linda; Hinton, Ladson; Rosen, Howard J; Ruhl, Mary

2017-08-01

Studying the brain through autopsy is an essential component of Alzheimer's disease research. Racial and ethnic minorities are underrepresented in Alzheimer's research generally and, in particular, in the number of completed brain autopsies. We explored beliefs about and attitudes toward brain donation among African American, Chinese, Caucasian, and Latino research subjects and their family members through focus groups at 4 NIH-funded Alzheimer's Disease Centers. Eighteen focus groups were conducted with 61 research subjects and 34 family members. Because the primary purpose of the focus groups was to identify the range of considerations that may influence the decision to participate in brain donation, data from focus groups were pooled and then analyzed. We found that many of the concerns, attitudes, and beliefs about brain donation were similar across the 4 ethnic groups. Concerns and attitudes fell into 3 categories: (a) concerns and misconceptions about brain research and the process of brain removal, (b) religious beliefs, and (c) the role of the family. Our findings suggest that interventions to enhance enrollment in brain donation that target factors identified in this study are likely to be relevant to people from a broad range of backgrounds and ethnicities. Nonetheless, we observed some potential differences among racial/ethnic groups that may affect how research volunteers and their families approach a decision about donating their brain for research. Further study is warranted to explore these and other possible culturally distinct attitudes and beliefs about brain donation. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Longitudinal relationship between traumatic brain injury and the risk of incident optic neuropathy: A 10-year follow-up nationally representative Taiwan survey

PubMed Central

Chen, Ying-Jen; Liang, Chang-Min; Tai, Ming-Cheng; Chang, Yun-Hsiang; Lin, Tzu-Yu; Chung, Chi-Hsiang; Lin, Fu-Huang; Tsao, Chang-Huei; Chien, Wu-Chien

2017-01-01

Accumulating evidences had shown that traumatic brain injury was associated with visual impairment or vision loss. However, there were a limited number of empirical studies regarding the longitudinal relationship between traumatic brain injury and incident optic neuropathy. We studied a cohort from the Taiwanese National Health Insurance data comprising 553918 participants with traumatic brain injury and optic neuropathy-free in the case group and 1107836 individuals without traumatic brain injury in the control group from 1st January 2000. After the index date until the end of 2010, Cox proportional hazards analysis was used to compare the risk of incident optic neuropathy. During the follow-up period, case group was more likely to develop incident optic neuropathy (0.24%) than the control group (0.11%). Multivariate Cox regression analysis demonstrated that the case group had a 3-fold increased risk of optic neuropathy (HR = 3.017, 95% CI = 2.767–3.289, p < 0.001). After stratification by demographic information, traumatic brain injury remained a significant factor for incident optic neuropathy. Our study provided evidence of the increased risk of incident optic neuropathy after traumatic brain injury during a 10-year follow-up period. Patients with traumatic brain injury required periodic and thorough eye examinations for incident optic neuropathy to prevent potentially irreversible vision loss. PMID:29156847

Longitudinal relationship between traumatic brain injury and the risk of incident optic neuropathy: A 10-year follow-up nationally representative Taiwan survey.

PubMed

Chen, Ying-Jen; Liang, Chang-Min; Tai, Ming-Cheng; Chang, Yun-Hsiang; Lin, Tzu-Yu; Chung, Chi-Hsiang; Lin, Fu-Huang; Tsao, Chang-Huei; Chien, Wu-Chien

2017-10-17

Accumulating evidences had shown that traumatic brain injury was associated with visual impairment or vision loss. However, there were a limited number of empirical studies regarding the longitudinal relationship between traumatic brain injury and incident optic neuropathy. We studied a cohort from the Taiwanese National Health Insurance data comprising 553918 participants with traumatic brain injury and optic neuropathy-free in the case group and 1107836 individuals without traumatic brain injury in the control group from 1st January 2000. After the index date until the end of 2010, Cox proportional hazards analysis was used to compare the risk of incident optic neuropathy. During the follow-up period, case group was more likely to develop incident optic neuropathy (0.24%) than the control group (0.11%). Multivariate Cox regression analysis demonstrated that the case group had a 3-fold increased risk of optic neuropathy (HR = 3.017, 95% CI = 2.767-3.289, p < 0.001). After stratification by demographic information, traumatic brain injury remained a significant factor for incident optic neuropathy. Our study provided evidence of the increased risk of incident optic neuropathy after traumatic brain injury during a 10-year follow-up period. Patients with traumatic brain injury required periodic and thorough eye examinations for incident optic neuropathy to prevent potentially irreversible vision loss.

A six-year longitudinal PET study of (+)-[11C]DTBZ binding to the VMAT2 in monkey brain.

PubMed

Kilbourn, Michael R; Koeppe, Robert A

2017-12-01

The longitudinal reproducibility of in vivo binding potential measures for [ 11 C]dihydrotetrabenazine ([ 11 C]DTBZ) binding to the vesicular monoamine transporter 2 (VMAT2) site in primate brain was examined using a unique dataset of repeated control PET imaging studies. Forty-one dynamic [ 11 C]DTBZ PET studies were completed in a single rhesus monkey. Imaging equipment (microPET P4), personnel, radiotracer characteristics (injected mass amounts, molar activity) and image data analysis (BP ND-Logan ) were consistent throughout the entire sequence of PET studies. Same day reproducibility of BP ND-Logan estimates of specific binding was very good (-3% and -7% changes) for two control-control sessions. Over the full 74 months, the average BP ND-Logan value for [ 11 C]DTBZ-PET studies was 4.19±0.52, for a variance of 12%. No age-dependent change in binding potentials was observed over the six-year period. If the technical variables associated with PET scanner are consistently maintained, including PET scanner, imaging procedures and radiotracer preparation, in vivo biochemistry can be reproducibly measured in the primate brain over a multi-year period of time. Copyright © 2017 Elsevier Inc. All rights reserved.

Single Subject Prediction of Brain Disorders in Neuroimaging: Promises and Pitfalls

PubMed Central

Arbabshirani, Mohammad R.; Plis, Sergey; Sui, Jing; Calhoun, Vince D.

2016-01-01

Neuroimaging-based single subject prediction of brain disorders has gained increasing attention in recent years. Using a variety of neuroimaging modalities such as structural, functional and diffusion MRI, along with machine learning techniques, hundreds of studies have been carried out for accurate classification of patients with heterogeneous mental and neurodegenerative disorders such as schizophrenia and Alzheimer's disease. More than 500 studies have been published during the past quarter century on single subject prediction focused on a multiple brain disorders. In the first part of this study, we provide a survey of more than 200 reports in this field with a focus on schizophrenia, mild cognitive impairment (MCI), Alzheimer's disease (AD), depressive disorders, autism spectrum disease (ASD) and attention-deficit hyperactivity disorder (ADHD). Detailed information about those studies such as sample size, type and number of extracted features and reported accuracy are summarized and discussed. To our knowledge, this is by far the most comprehensive review of neuroimaging-based single subject prediction of brain disorders. In the second part, we present our opinion on major pitfalls of those studies from a machine learning point of view. Common biases are discussed and suggestions are provided. Moreover, emerging trends such as decentralized data sharing, multimodal brain imaging, differential diagnosis, disease subtype classification and deep learning are also discussed. Based on this survey, there are extensive evidences showing the great potential of neuroimaging data for single subject prediction of various disorders. However, the main bottleneck of this exciting field is still the limited sample size, which could be potentially addressed by modern data sharing models such as the ones discussed in this paper. Emerging big data technologies and advanced data-intensive machine learning methodologies such as deep learning have coincided with an increasing need for accurate, robust and generalizable single subject prediction of brain disorders during an exciting time. In this report, we survey the past and offer some opinions regarding the road ahead. PMID:27012503

Single subject prediction of brain disorders in neuroimaging: Promises and pitfalls.

PubMed

Arbabshirani, Mohammad R; Plis, Sergey; Sui, Jing; Calhoun, Vince D

2017-01-15

Neuroimaging-based single subject prediction of brain disorders has gained increasing attention in recent years. Using a variety of neuroimaging modalities such as structural, functional and diffusion MRI, along with machine learning techniques, hundreds of studies have been carried out for accurate classification of patients with heterogeneous mental and neurodegenerative disorders such as schizophrenia and Alzheimer's disease. More than 500 studies have been published during the past quarter century on single subject prediction focused on a multiple brain disorders. In the first part of this study, we provide a survey of more than 200 reports in this field with a focus on schizophrenia, mild cognitive impairment (MCI), Alzheimer's disease (AD), depressive disorders, autism spectrum disease (ASD) and attention-deficit hyperactivity disorder (ADHD). Detailed information about those studies such as sample size, type and number of extracted features and reported accuracy are summarized and discussed. To our knowledge, this is by far the most comprehensive review of neuroimaging-based single subject prediction of brain disorders. In the second part, we present our opinion on major pitfalls of those studies from a machine learning point of view. Common biases are discussed and suggestions are provided. Moreover, emerging trends such as decentralized data sharing, multimodal brain imaging, differential diagnosis, disease subtype classification and deep learning are also discussed. Based on this survey, there is extensive evidence showing the great potential of neuroimaging data for single subject prediction of various disorders. However, the main bottleneck of this exciting field is still the limited sample size, which could be potentially addressed by modern data sharing models such as the ones discussed in this paper. Emerging big data technologies and advanced data-intensive machine learning methodologies such as deep learning have coincided with an increasing need for accurate, robust and generalizable single subject prediction of brain disorders during an exciting time. In this report, we survey the past and offer some opinions regarding the road ahead. Copyright © 2016 Elsevier Inc. All rights reserved.

Re-evaluating the link between brain size and behavioural ecology in primates.

PubMed

Powell, Lauren E; Isler, Karin; Barton, Robert A

2017-10-25

Comparative studies have identified a wide range of behavioural and ecological correlates of relative brain size, with results differing between taxonomic groups, and even within them. In primates for example, recent studies contradict one another over whether social or ecological factors are critical. A basic assumption of such studies is that with sufficiently large samples and appropriate analysis, robust correlations indicative of selection pressures on cognition will emerge. We carried out a comprehensive re-examination of correlates of primate brain size using two large comparative datasets and phylogenetic comparative methods. We found evidence in both datasets for associations between brain size and ecological variables (home range size, diet and activity period), but little evidence for an effect of social group size, a correlation which has previously formed the empirical basis of the Social Brain Hypothesis. However, reflecting divergent results in the literature, our results exhibited instability across datasets, even when they were matched for species composition and predictor variables. We identify several potential empirical and theoretical difficulties underlying this instability and suggest that these issues raise doubts about inferring cognitive selection pressures from behavioural correlates of brain size. © 2017 The Author(s).

DHA Effects in Brain Development and Function

PubMed Central

Lauritzen, Lotte; Brambilla, Paolo; Mazzocchi, Alessandra; Harsløf, Laurine B. S.; Ciappolino, Valentina; Agostoni, Carlo

2016-01-01

Docosahexaenoic acid (DHA) is a structural constituent of membranes specifically in the central nervous system. Its accumulation in the fetal brain takes place mainly during the last trimester of pregnancy and continues at very high rates up to the end of the second year of life. Since the endogenous formation of DHA seems to be relatively low, DHA intake may contribute to optimal conditions for brain development. We performed a narrative review on research on the associations between DHA levels and brain development and function throughout the lifespan. Data from cell and animal studies justify the indication of DHA in relation to brain function for neuronal cell growth and differentiation as well as in relation to neuronal signaling. Most data from human studies concern the contribution of DHA to optimal visual acuity development. Accumulating data indicate that DHA may have effects on the brain in infancy, and recent studies indicate that the effect of DHA may depend on gender and genotype of genes involved in the endogenous synthesis of DHA. While DHA levels may affect early development, potential effects are also increasingly recognized during childhood and adult life, suggesting a role of DHA in cognitive decline and in relation to major psychiatric disorders. PMID:26742060

DHA Effects in Brain Development and Function.

PubMed

Lauritzen, Lotte; Brambilla, Paolo; Mazzocchi, Alessandra; Harsløf, Laurine B S; Ciappolino, Valentina; Agostoni, Carlo

2016-01-04

Docosahexaenoic acid (DHA) is a structural constituent of membranes specifically in the central nervous system. Its accumulation in the fetal brain takes place mainly during the last trimester of pregnancy and continues at very high rates up to the end of the second year of life. Since the endogenous formation of DHA seems to be relatively low, DHA intake may contribute to optimal conditions for brain development. We performed a narrative review on research on the associations between DHA levels and brain development and function throughout the lifespan. Data from cell and animal studies justify the indication of DHA in relation to brain function for neuronal cell growth and differentiation as well as in relation to neuronal signaling. Most data from human studies concern the contribution of DHA to optimal visual acuity development. Accumulating data indicate that DHA may have effects on the brain in infancy, and recent studies indicate that the effect of DHA may depend on gender and genotype of genes involved in the endogenous synthesis of DHA. While DHA levels may affect early development, potential effects are also increasingly recognized during childhood and adult life, suggesting a role of DHA in cognitive decline and in relation to major psychiatric disorders.

A step into the anarchist's mind: examining political attitudes and ideology through event-related brain potentials.

PubMed

Dhont, Kristof; Van Hiel, Alain; Pattyn, Sven; Onraet, Emma; Severens, Els

2012-03-01

The present study investigates patterns of event-related brain potentials following the presentation of attitudinal stimuli among political moderates (N=12) and anarchists (N=11). We used a modified oddball paradigm to investigate the evaluative inconsistency effect elicited by stimuli embedded in a sequence of contextual stimuli with an opposite valence. Increased late positive potentials (LPPs) of extreme political attitudes were observed. Moreover, this LPP enhancement was larger among anarchists than among moderates, indicating that an extreme political attitude of a moderate differs from an extreme political attitude of an anarchist. The discussion elaborates on the meaning of attitude extremity for moderates and extremists. © The Author (2011). Published by Oxford University Press.

Dogs cannot bark: event-related brain responses to true and false negated statements as indicators of higher-order conscious processing.

PubMed

Herbert, Cornelia; Kübler, Andrea

2011-01-01

The present study investigated event-related brain potentials elicited by true and false negated statements to evaluate if discrimination of the truth value of negated information relies on conscious processing and requires higher-order cognitive processing in healthy subjects across different levels of stimulus complexity. The stimulus material consisted of true and false negated sentences (sentence level) and prime-target expressions (word level). Stimuli were presented acoustically and no overt behavioral response of the participants was required. Event-related brain potentials to target words preceded by true and false negated expressions were analyzed both within group and at the single subject level. Across the different processing conditions (word pairs and sentences), target words elicited a frontal negativity and a late positivity in the time window from 600-1000 msec post target word onset. Amplitudes of both brain potentials varied as a function of the truth value of the negated expressions. Results were confirmed at the single-subject level. In sum, our results support recent suggestions according to which evaluation of the truth value of a negated expression is a time- and cognitively demanding process that cannot be solved automatically, and thus requires conscious processing. Our paradigm provides insight into higher-order processing related to language comprehension and reasoning in healthy subjects. Future studies are needed to evaluate if our paradigm also proves sensitive for the detection of consciousness in non-responsive patients.

Effective brain network analysis with resting-state EEG data: a comparison between heroin abstinent and non-addicted subjects

NASA Astrophysics Data System (ADS)

Hu, Bin; Dong, Qunxi; Hao, Yanrong; Zhao, Qinglin; Shen, Jian; Zheng, Fang

2017-08-01

Objective. Neuro-electrophysiological tools have been widely used in heroin addiction studies. Previous studies indicated that chronic heroin abuse would result in abnormal functional organization of the brain, while few heroin addiction studies have applied the effective connectivity tool to analyze the brain functional system (BFS) alterations induced by heroin abuse. The present study aims to identify the abnormality of resting-state heroin abstinent BFS using source decomposition and effective connectivity tools. Approach. The resting-state electroencephalograph (EEG) signals were acquired from 15 male heroin abstinent (HA) subjects and 14 male non-addicted (NA) controls. Multivariate autoregressive models combined independent component analysis (MVARICA) was applied for blind source decomposition. Generalized partial directed coherence (GPDC) was applied for effective brain connectivity analysis. Effective brain networks of both HA and NA groups were constructed. The two groups of effective cortical networks were compared by the bootstrap method. Abnormal causal interactions between decomposed source regions were estimated in the 1-45 Hz frequency domain. Main results. This work suggested: (a) there were clear effective network alterations in heroin abstinent subject groups; (b) the parietal region was a dominant hub of the abnormally weaker causal pathways, and the left occipital region was a dominant hub of the abnormally stronger causal pathways. Significance. These findings provide direct evidence that chronic heroin abuse induces brain functional abnormalities. The potential value of combining effective connectivity analysis and brain source decomposition methods in exploring brain alterations of heroin addicts is also implied.

Effective brain network analysis with resting-state EEG data: a comparison between heroin abstinent and non-addicted subjects.

PubMed

Hu, Bin; Dong, Qunxi; Hao, Yanrong; Zhao, Qinglin; Shen, Jian; Zheng, Fang

2017-08-01

Neuro-electrophysiological tools have been widely used in heroin addiction studies. Previous studies indicated that chronic heroin abuse would result in abnormal functional organization of the brain, while few heroin addiction studies have applied the effective connectivity tool to analyze the brain functional system (BFS) alterations induced by heroin abuse. The present study aims to identify the abnormality of resting-state heroin abstinent BFS using source decomposition and effective connectivity tools. The resting-state electroencephalograph (EEG) signals were acquired from 15 male heroin abstinent (HA) subjects and 14 male non-addicted (NA) controls. Multivariate autoregressive models combined independent component analysis (MVARICA) was applied for blind source decomposition. Generalized partial directed coherence (GPDC) was applied for effective brain connectivity analysis. Effective brain networks of both HA and NA groups were constructed. The two groups of effective cortical networks were compared by the bootstrap method. Abnormal causal interactions between decomposed source regions were estimated in the 1-45 Hz frequency domain. This work suggested: (a) there were clear effective network alterations in heroin abstinent subject groups; (b) the parietal region was a dominant hub of the abnormally weaker causal pathways, and the left occipital region was a dominant hub of the abnormally stronger causal pathways. These findings provide direct evidence that chronic heroin abuse induces brain functional abnormalities. The potential value of combining effective connectivity analysis and brain source decomposition methods in exploring brain alterations of heroin addicts is also implied.

INVESTIGATING DIFFERENCES IN BRAIN FUNCTIONAL NETWORKS USING HIERARCHICAL COVARIATE-ADJUSTED INDEPENDENT COMPONENT ANALYSIS.

PubMed

Shi, Ran; Guo, Ying

2016-12-01

Human brains perform tasks via complex functional networks consisting of separated brain regions. A popular approach to characterize brain functional networks in fMRI studies is independent component analysis (ICA), which is a powerful method to reconstruct latent source signals from their linear mixtures. In many fMRI studies, an important goal is to investigate how brain functional networks change according to specific clinical and demographic variabilities. Existing ICA methods, however, cannot directly incorporate covariate effects in ICA decomposition. Heuristic post-ICA analysis to address this need can be inaccurate and inefficient. In this paper, we propose a hierarchical covariate-adjusted ICA (hc-ICA) model that provides a formal statistical framework for estimating covariate effects and testing differences between brain functional networks. Our method provides a more reliable and powerful statistical tool for evaluating group differences in brain functional networks while appropriately controlling for potential confounding factors. We present an analytically tractable EM algorithm to obtain maximum likelihood estimates of our model. We also develop a subspace-based approximate EM that runs significantly faster while retaining high accuracy. To test the differences in functional networks, we introduce a voxel-wise approximate inference procedure which eliminates the need of computationally expensive covariance matrix estimation and inversion. We demonstrate the advantages of our methods over the existing method via simulation studies. We apply our method to an fMRI study to investigate differences in brain functional networks associated with post-traumatic stress disorder (PTSD).

Structural imaging of the brain reveals decreased total brain and total gray matter volumes in obese but not in lean women with polycystic ovary syndrome compared to body mass index-matched counterparts.

PubMed

Ozgen Saydam, Basak; Has, Arzu Ceylan; Bozdag, Gurkan; Oguz, Kader Karli; Yildiz, Bulent Okan

2017-07-01

To detect differences in global brain volumes and identify relations between brain volume and appetite-related hormones in women with polycystic ovary syndrome (PCOS) compared to body mass index-matched controls. Forty subjects participated in this study. Cranial magnetic resonance imaging and measurements of fasting ghrelin, leptin and glucagon-like peptide 1 (GLP-1), as well as GLP-1 levels during mixed-meal tolerance test (MTT), were performed. Total brain volume and total gray matter volume (GMV) were decreased in obese PCOS compared to obese controls (p < 0.05 for both) whereas lean PCOS and controls did not show a significant difference. Secondary analyses of regional brain volumes showed decreases in GMV of the caudate nucleus, ventral diencephalon and hippocampus in obese PCOS compared to obese controls (p < 0.05 for all), whereas lean patients with PCOS had lower GMV in the amygdala than lean controls (p < 0.05). No significant relations were detected between structural differences and measured hormone levels at baseline or during MTT. This study, investigating structural brain alterations in PCOS, suggests volumetric reductions in global brain areas in obese women with PCOS. Functional studies with larger sample size are needed to determine physiopathological roles of these changes and potential effects of long-term medical management on brain structure of PCOS.

Brain tumors in children and occupational exposure of parents.

PubMed

Peters, F M; Preston-Martin, S; Yu, M C

1981-07-10

Ninety-two cases of brain tumor in children less than 10 years old were compared with 92 matched controls for parental occupational history. Cases were more likely than controls to show material occupations involving chemical exposure, paternal occupations involving solvents, and employment of father in the aircraft industry. These three factors were not affected by adjustment for the potential confounding variables examined in this study.

The Origins of Word Learning: Brain Responses of 3-Month-Olds Indicate Their Rapid Association of Objects and Words

ERIC Educational Resources Information Center

Friedrich, Manuela; Friederici, Angela D.

2017-01-01

The present study explored the origins of word learning in early infancy. Using event-related potentials (ERP) we monitored the brain activity of 3-month-old infants when they were repeatedly exposed to several initially novel words paired consistently with each the same initially novel objects or inconsistently with different objects. Our results…

Does oral care contribute to brain activation?: One case of functional near-infrared spectroscopy study in patients with a persistent disturbance of consciousness.

PubMed

Fujii, Wataru; Kanamori, Daisuke; Nagata, Chisato; Sakaguchi, Kiyomi; Watanabe, Risa

2014-08-01

We used functional near-infrared spectroscopy (fNIRS) to measure cerebral blood flow during oral care in a patient with persistent disturbance of consciousness. We experienced that cerebral blood flow to frontal area increased during oral care, suggesting that oral care may have a potential role in rehabilitation for the brain.

Fisetin as a caloric restriction mimetic protects rat brain against aging induced oxidative stress, apoptosis and neurodegeneration.

PubMed

Singh, Sandeep; Singh, Abhishek Kumar; Garg, Geetika; Rizvi, Syed Ibrahim

2018-01-15

In the present study, attempts have been made to evaluate the potential role of fisetin, a caloric restriction mimetic (CRM), for neuroprotection in D-galactose (D-gal) induced accelerated and natural aging models of rat. Fisetin was supplemented (15mg/kg b.w., orally) to young, D-gal induced aged (D-gal 500mg/kg b.w subcutaneously) and naturally aged rats for 6weeks. Standard protocols were employed to measure pro-oxidants, antioxidants and mitochondrial membrane potential in brain tissues. Gene expression analysis with reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to assess the expression of autophagy, neuronal, aging as well as inflammatory marker genes. We have also evaluated apoptotic cell death and synaptosomal membrane-bound ion transporter activities in brain tissues. Our data demonstrated that fisetin significantly decreased the level of pro-oxidants and increased the level of antioxidants. Furthermore, fisetin also ameliorated mitochondrial membrane depolarization, apoptotic cell death and impairments in the activities of synaptosomal membrane-bound ion transporters in aging rat brain. RT-PCR data revealed that fisetin up-regulated the expression of autophagy genes (Atg-3 and Beclin-1), sirtuin-1 and neuronal markers (NSE and Ngb), and down-regulated the expression of inflammatory (IL-1β and TNF-α) and Sirt-2 genes respectively in aging brain. The present study suggests that fisetin supplementation may provide neuroprotection against aging-induced oxidative stress, apoptotic cell death, neuro-inflammation, and neurodegeneration in rat brain. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of Grape Skin Extract on Age-Related Mitochondrial Dysfunction, Memory and Life Span in C57BL/6J Mice.

PubMed

Asseburg, Heike; Schäfer, Carmina; Müller, Madeleine; Hagl, Stephanie; Pohland, Maximilian; Berressem, Dirk; Borchiellini, Marta; Plank, Christina; Eckert, Gunter P

2016-09-01

Dementia contributes substantially to the burden of disability experienced at old age, and mitochondrial dysfunction (MD) was identified as common final pathway in brain aging and Alzheimer's disease. Due to its early appearance, MD is a promising target for nutritional prevention strategies and polyphenols as potential neurohormetic inducers may be strong neuroprotective candidates. This study aimed to investigate the effects of a polyphenol-rich grape skin extract (PGE) on age-related dysfunctions of brain mitochondria, memory, life span and potential hormetic pathways in C57BL/6J mice. PGE was administered at a dose of 200 mg/kg body weight/d in a 3-week short-term, 6-month long-term and life-long study. MD in the brains of aged mice (19-22 months old) compared to young mice (3 months old) was demonstrated by lower ATP levels and by impaired mitochondrial respiratory complex activity (except for mice treated with antioxidant-depleted food pellets). Long-term PGE feeding partly enhanced brain mitochondrial respiration with only minor beneficial effect on brain ATP levels and memory of aged mice. Life-long PGE feeding led to a transient but significant shift of survival curve toward higher survival rates but without effect on the overall survival. The moderate effects of PGE were associated with elevated SIRT1 but not SIRT3 mRNA expressions in brain and liver tissue. The beneficial effects of the grape extract may have been influenced by the profile of bioavailable polyphenols and the starting point of interventions.

Event-related potentials in response to emotional words in patients with major depressive disorder and healthy controls.

PubMed

Liu, Hong; Yin, Hui-fang; Wu, Da-xing; Xu, Shu-jing

2014-01-01

Dysfunctional cognitive processing and abnormal brain activation in response to emotional stimuli have long been recognized as core features of the major depressive disorder (MDD). The aim of this study was to examine how Chinese patients with MDD process Chinese emotional words presented to either the left (LH) or right hemisphere (RH). Reaction time (RT) and the late positive component of the event-related potential were measured while subjects judged the valence (positive or negative) of emotional words written in Chinese. Compared to healthy controls, patients with MDD exhibited slower RTs in response to negative words. In all subjects, the RTs in response to negative words were significantly faster than RTs in response to positive words presented to the LH, as well as significantly faster than responses to negative words presented to the RH. Compared to healthy controls, MDD patients exhibited reduced activation of the central and left regions of the brain in response to both negative and positive words. In healthy controls, the posterior brain areas were more active than the anterior brain areas when responding to negative words. All individuals showed faster RTs in response to negative words compared to positive words. In addition, MDD patients showed lateralization of brain activity in response to emotional words, whereas healthy individuals did not show this lateralization. Posterior brain areas appear to play an especially important role in discriminating and experiencing negative emotional words. This study provides further evidence in support of the negative bias hypothesis and the emotional processing theory.

Construction of population-specific Indian MRI brain template: Morphometric comparison with Chinese and Caucasian templates.

PubMed

Bhalerao, Gaurav Vivek; Parlikar, Rujuta; Agrawal, Rimjhim; Shivakumar, Venkataram; Kalmady, Sunil V; Rao, Naren P; Agarwal, Sri Mahavir; Narayanaswamy, Janardhanan C; Reddy, Y C Janardhan; Venkatasubramanian, Ganesan

2018-06-01

Spatial normalization of brain MR images is highly dependent on the choice of target brain template. Morphological differences caused by factors like genetic and environmental exposures, generates a necessity to construct population specific brain templates. Brain image analysis performed using brain templates from Caucasian population may not be appropriate for non-Caucasian population. In this study, our objective was to construct an Indian brain template from a large population (N = 157 subjects) and compare the morphometric parameters of this template with that of Chinese-56 and MNI-152 templates. In addition, using an independent MRI data of 15 Indian subjects, we also evaluated the potential registration accuracy differences using these three templates. Indian brain template was constructed using iterative routines as per established procedures. We compared our Indian template with standard MNI-152 template and Chinese template by measuring global brain features. We also examined accuracy of registration by aligning 15 new Indian brains to Indian, Chinese and MNI templates. Furthermore, we supported our measurement protocol with inter-rater and intra-rater reliability analysis. Our results showed that there were significant differences in global brain features of Indian template in comparison with Chinese and MNI brain templates. The results of registration accuracy analysis revealed that fewer deformations are required when Indian brains are registered to Indian template as compared to Chinese and MNI templates. This study concludes that population specific Indian template is likely to be more appropriate for structural and functional image analysis of Indian population. Copyright © 2018 Elsevier B.V. All rights reserved.

Surface modified PLGA nanoparticles for brain targeting of Bacoside-A.

PubMed

Jose, S; Sowmya, S; Cinu, T A; Aleykutty, N A; Thomas, S; Souto, E B

2014-10-15

The present paper focuses on the development and in vitro/in vivo characterization of nanoparticles composed of poly-(D,L)-Lactide-co-Glycolide (PLGA) loading Bacoside-A, as a new approach for the brain delivery of the neuroprotective drug for the treatment of neurodegenerative disorders (e.g. Alzheimer Disease). Bacoside-A-loaded PLGA nanoparticles were prepared via o/w emulsion solvent evaporation technique. Surface of the nanoparticles were modified by coating with polysorbate 80 to facilitate the crossing of the blood brain barrier (BBB), and the processing parameters (i.e. sonication time, the concentration of polymer (PLGA) and surfactant (polysorbate 80), and drug-polymer ratio) were optimized with the aim to achieve a high production yield. Brain targeting potential of the nanoparticles was evaluated by in vivo studies using Wistar albino rats. The nanoparticles produced by optimal formulation were within the nanosized range (70-200 nm) with relatively low polydispersity index (0.391 ± 1.2). The encapsulation efficiency of Bacoside-A in PLGA nanoparticles was 57.11 ± 7.11%, with a drug loading capacity of 20.5 ± 1.98%. SEM images showed the spherical shape of the PLGA nanoparticles, whereas their low crystallinity was demonstrated by X-ray studies, which also confirmed no chemical interactions between the drug and polymer molecules. The in vitro release of Bacoside-A from the PLGA nanoparticles followed a sustained release pattern with a maximum release of up to 83.04 ± 2.55% in 48 h. When compared to pure drug solution (2.56 ± 1.23 μg/g tissue), in vivo study demonstrated higher brain concentration of Bacoside-A (23.94 ± 1.74 μg/g tissue) suggesting a significant role of surface coated nanoparticles on brain targeting. The results indicate the potential of surface modified PLGA nanoparticles for the delivery of Bacoside-A to the brain. Copyright © 2014 Elsevier B.V. All rights reserved.

Attentional Mechanisms in Sports via Brain-Electrical Event-Related Potentials

ERIC Educational Resources Information Center

Hack, Johannes; Memmert, Daniel; Rup, Andre

2009-01-01

In this study, we examined attention processes in complex, sport-specific decision-making tasks without interdependencies from anticipation. Psychophysiological and performance data recorded from advanced and intermediate level basketball referees were compared. Event-related potentials obtained while judging game situations in foul recognition…

Enhanced functional connectivity and volume between cognitive and reward centers of naïve rodent brain produced by pro-dopaminergic agent KB220Z

PubMed Central

Badgaiyan, Rajendra D.; Thanos, Panayotis K.; Kulkarni, Praveen; Giordano, John; Baron, David; Gold, Mark S.

2017-01-01

Dopaminergic reward dysfunction in addictive behaviors is well supported in the literature. There is evidence that alterations in synchronous neural activity between brain regions subserving reward and various cognitive functions may significantly contribute to substance-related disorders. This study presents the first evidence showing that a pro-dopaminergic nutraceutical (KB220Z) significantly enhances, above placebo, functional connectivity between reward and cognitive brain areas in the rat. These include the nucleus accumbens, anterior cingulate gyrus, anterior thalamic nuclei, hippocampus, prelimbic and infralimbic loci. Significant functional connectivity, increased brain connectivity volume recruitment (potentially neuroplasticity), and dopaminergic functionality were found across the brain reward circuitry. Increases in functional connectivity were specific to these regions and were not broadly distributed across the brain. While these initial findings have been observed in drug naïve rodents, this robust, yet selective response implies clinical relevance for addicted individuals at risk for relapse, who show reductions in functional connectivity after protracted withdrawal. Future studies will evaluate KB220Z in animal models of addiction. PMID:28445527

Separating neural and vascular effects of caffeine using simultaneous EEG–FMRI: Differential effects of caffeine on cognitive and sensorimotor brain responses

PubMed Central

Diukova, Ana; Ware, Jennifer; Smith, Jessica E.; Evans, C. John; Murphy, Kevin; Rogers, Peter J.; Wise, Richard G.

2012-01-01

The effects of caffeine are mediated through its non-selective antagonistic effects on adenosine A1 and A2A adenosine receptors resulting in increased neuronal activity but also vasoconstriction in the brain. Caffeine, therefore, can modify BOLD FMRI signal responses through both its neural and its vascular effects depending on receptor distributions in different brain regions. In this study we aim to distinguish neural and vascular influences of a single dose of caffeine in measurements of task-related brain activity using simultaneous EEG–FMRI. We chose to compare low-level visual and motor (paced finger tapping) tasks with a cognitive (auditory oddball) task, with the expectation that caffeine would differentially affect brain responses in relation to these tasks. To avoid the influence of chronic caffeine intake, we examined the effect of 250 mg of oral caffeine on 14 non and infrequent caffeine consumers in a double-blind placebo-controlled cross-over study. Our results show that the task-related BOLD signal change in visual and primary motor cortex was significantly reduced by caffeine, while the amplitude and latency of visual evoked potentials over occipital cortex remained unaltered. However, during the auditory oddball task (target versus non-target stimuli) caffeine significantly increased the BOLD signal in frontal cortex. Correspondingly, there was also a significant effect of caffeine in reducing the target evoked response potential (P300) latency in the oddball task and this was associated with a positive potential over frontal cortex. Behavioural data showed that caffeine also improved performance in the oddball task with a significantly reduced number of missed responses. Our results are consistent with earlier studies demonstrating altered flow-metabolism coupling after caffeine administration in the context of our observation of a generalised caffeine-induced reduction in cerebral blood flow demonstrated by arterial spin labelling (19% reduction over grey matter). We were able to identify vascular effects and hence altered neurovascular coupling through the alteration of low-level task FMRI responses in the face of a preserved visual evoked potential. However, our data also suggest a cognitive effect of caffeine through its positive effect on the frontal BOLD signal consistent with the shortening of oddball EEG response latency. The combined use of EEG–FMRI is a promising methodology for investigating alterations in brain function in drug and disease studies where neurovascular coupling may be altered on a regional basis. PMID:22561357

At the centennial of Michaelis and Menten, competing Michaelis-Menten steps explain effect of GLP-1 on blood-brain transfer and metabolism of glucose.

PubMed

Gejl, Michael; Rungby, Jørgen; Brock, Birgitte; Gjedde, Albert

2014-08-01

Glucagon-like peptide-1 (GLP-1) is a potent insulinotropic incretin hormone with both pancreatic and extrapancreatic effects. Studies of GLP-1 reveal significant effects in regions of brain tissue that regulate appetite and satiety. GLP-1 mimetics are used for the treatment of type 2 diabetes mellitus. GLP-1 interacts with peripheral functions in which the autonomic nervous system plays an important role, and emerging pre-clinical findings indicate a potential neuroprotective role of the peptide, for example in models of stroke and in neurodegenerative disorders. A century ago, Leonor Michaelis and Maud Menten described the steady-state enzyme kinetics that still apply to the multiple receptors, transporters and enzymes that define the biochemical reactions of the brain, including the glucose-dependent impact of GLP-1 on blood-brain glucose transfer and metabolism. This MiniReview examines the potential of GLP-1 as a molecule of interest for the understanding of brain energy metabolism and with reference to the impact on brain metabolism related to appetite and satiety regulation, stroke and neurodegenerative disorders. These effects can be understood only by reference to the original formulation of the Michaelis-Menten equation as applied to a chain of kinetically controlled steps. Indeed, the effects of GLP-1 receptor activation on blood-brain glucose transfer and brain metabolism of glucose depend on the glucose concentration and relative affinities of the steps both in vitro and in vivo, as in the pancreas. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Increased brain lactate is central to the development of brain edema in rats with chronic liver disease.

PubMed

Bosoi, Cristina R; Zwingmann, Claudia; Marin, Helen; Parent-Robitaille, Christian; Huynh, Jimmy; Tremblay, Mélanie; Rose, Christopher F

2014-03-01

The pathogenesis of brain edema in patients with chronic liver disease (CLD) and minimal hepatic encephalopathy (HE) remains undefined. This study evaluated the role of brain lactate, glutamine and organic osmolytes, including myo-inositol and taurine, in the development of brain edema in a rat model of cirrhosis. Six-week bile-duct ligated (BDL) rats were injected with (13)C-glucose and de novo synthesis of lactate, and glutamine in the brain was quantified using (13)C nuclear magnetic resonance spectroscopy (NMR). Total brain lactate, glutamine, and osmolytes were measured using (1)H NMR or high performance liquid chromatography. To further define the interplay between lactate, glutamine and brain edema, BDL rats were treated with AST-120 (engineered activated carbon microspheres) and dichloroacetate (DCA: lactate synthesis inhibitor). Significant increases in de novo synthesis of lactate (1.6-fold, p<0.001) and glutamine (2.2-fold, p<0.01) were demonstrated in the brains of BDL rats vs. SHAM-operated controls. Moreover, a decrease in cerebral myo-inositol (p<0.001), with no change in taurine, was found in the presence of brain edema in BDL rats vs. controls. BDL rats treated with either AST-120 or DCA showed attenuation in brain edema and brain lactate. These two treatments did not lead to similar reductions in brain glutamine. Increased brain lactate, and not glutamine, is a primary player in the pathogenesis of brain edema in CLD. In addition, alterations in the osmoregulatory response may also be contributing factors. Our results suggest that inhibiting lactate synthesis is a new potential target for the treatment of HE. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Brain Functional Connectivity in Small Cell Lung Cancer Population after Chemotherapy Treatment: an ICA fMRI Study

NASA Astrophysics Data System (ADS)

Bromis, K.; Kakkos, I.; Gkiatis, K.; Karanasiou, I. S.; Matsopoulos, G. K.

2017-11-01

Previous neurocognitive assessments in Small Cell Lung Cancer (SCLC) population, highlight the presence of neurocognitive impairments (mainly in attention processing and executive functioning) in this type of cancer. The majority of these studies, associate these deficits with the Prophylactic Cranial Irradiation (PCI) that patients undergo in order to avoid brain metastasis. However, there is not much evidence exploring cognitive impairments induced by chemotherapy in SCLC patients. For this reason, we aimed to investigate the underlying processes that may potentially affect cognition by examining brain functional connectivity in nineteen SCLC patients after chemotherapy treatment, while additionally including fourteen healthy participants as control group. Independent Component Analysis (ICA) is a functional connectivity measure aiming to unravel the temporal correlation between brain regions, which are called brain networks. We focused on two brain networks related to the aforementioned cognitive functions, the Default Mode Network (DMN) and the Task-Positive Network (TPN). Permutation tests were performed between the two groups to assess the differences and control for familywise errors in the statistical parametric maps. ICA analysis showed functional connectivity disruptions within both of the investigated networks. These results, propose a detrimental effect of chemotherapy on brain functioning in the SCLC population.

Fetal Stress and Programming of Hypoxic/Ischemic-Sensitive Phenotype in the Neonatal Brain: Mechanisms and Possible Interventions

PubMed Central

Li, Yong; Gonzalez, Pablo; Zhang, Lubo

2012-01-01

Growing evidence of epidemiological, clinical and experimental studies has clearly shown a close link between adverse in utero environment and the increased risk of neurological, psychological and psychiatric disorders in later life. Fetal stresses, such as hypoxia, malnutrition, and fetal exposure to nicotine, alcohol, cocaine and glucocorticoids may directly or indirectly act at cellular and molecular levels to alter the brain development and result in programming of heightened brain vulnerability to hypoxic-ischemic encephalopathy and the development of neurological diseases in the postnatal life. The underlying mechanisms are not well understood. However, glucocorticoids may play a crucial role in epigenetic programming of neurological disorders of fetal origins. This review summarizes the recent studies about the effects of fetal stress on the abnormal brain development, focusing on the cellular, molecular and epigenetic mechanisms and highlighting the central effects of glucocorticoids on programming of hypoxicischemic-sensitive phenotype in the neonatal brain, which may enhance the understanding of brain pathophysiology resulting from fetal stress and help explore potential targets of timely diagnosis, prevention and intervention in neonatal hypoxic-ischemic encephalopathy and other for brain disorders. PMID:22627492

Resting state network topology of the ferret brain.

PubMed

Zhou, Zhe Charles; Salzwedel, Andrew P; Radtke-Schuller, Susanne; Li, Yuhui; Sellers, Kristin K; Gilmore, John H; Shih, Yen-Yu Ian; Fröhlich, Flavio; Gao, Wei

2016-12-01

Resting state functional magnetic resonance imaging (rsfMRI) has emerged as a versatile tool for non-invasive measurement of functional connectivity patterns in the brain. RsfMRI brain dynamics in rodents, non-human primates, and humans share similar properties; however, little is known about the resting state functional connectivity patterns in the ferret, an animal model with high potential for developmental and cognitive translational study. To address this knowledge-gap, we performed rsfMRI on anesthetized ferrets using a 9.4T MRI scanner, and subsequently performed group-level independent component analysis (gICA) to identify functionally connected brain networks. Group-level ICA analysis revealed distributed sensory, motor, and higher-order networks in the ferret brain. Subsequent connectivity analysis showed interconnected higher-order networks that constituted a putative default mode network (DMN), a network that exhibits altered connectivity in neuropsychiatric disorders. Finally, we assessed ferret brain topological efficiency using graph theory analysis and found that the ferret brain exhibits small-world properties. Overall, these results provide additional evidence for pan-species resting-state networks, further supporting ferret-based studies of sensory and cognitive function. Copyright © 2016 Elsevier Inc. All rights reserved.

Perturbation of Brain Oscillations after Ischemic Stroke: A Potential Biomarker for Post-Stroke Function and Therapy

PubMed Central

Rabiller, Gratianne; He, Ji-Wei; Nishijima, Yasuo; Wong, Aaron; Liu, Jialing

2015-01-01

Brain waves resonate from the generators of electrical current and propagate across brain regions with oscillation frequencies ranging from 0.05 to 500 Hz. The commonly observed oscillatory waves recorded by an electroencephalogram (EEG) in normal adult humans can be grouped into five main categories according to the frequency and amplitude, namely δ (1–4 Hz, 20–200 μV), θ (4–8 Hz, 10 μV), α (8–12 Hz, 20–200 μV), β (12–30 Hz, 5–10 μV), and γ (30–80 Hz, low amplitude). Emerging evidence from experimental and human studies suggests that groups of function and behavior seem to be specifically associated with the presence of each oscillation band, although the complex relationship between oscillation frequency and function, as well as the interaction between brain oscillations, are far from clear. Changes of brain oscillation patterns have long been implicated in the diseases of the central nervous system including ischemic stroke, in which the reduction of cerebral blood flow as well as the progression of tissue damage have direct spatiotemporal effects on the power of several oscillatory bands and their interactions. This review summarizes the current knowledge in behavior and function associated with each brain oscillation, and also in the specific changes in brain electrical activities that correspond to the molecular events and functional alterations observed after experimental and human stroke. We provide the basis of the generations of brain oscillations and potential cellular and molecular mechanisms underlying stroke-induced perturbation. We will also discuss the implications of using brain oscillation patterns as biomarkers for the prediction of stroke outcome and therapeutic efficacy. PMID:26516838

Altered small-world topology of structural brain networks in infants with intrauterine growth restriction and its association with later neurodevelopmental outcome.

PubMed

Batalle, Dafnis; Eixarch, Elisenda; Figueras, Francesc; Muñoz-Moreno, Emma; Bargallo, Nuria; Illa, Miriam; Acosta-Rojas, Ruthy; Amat-Roldan, Ivan; Gratacos, Eduard

2012-04-02

Intrauterine growth restriction (IUGR) due to placental insufficiency affects 5-10% of all pregnancies and it is associated with a wide range of short- and long-term neurodevelopmental disorders. Prediction of neurodevelopmental outcomes in IUGR is among the clinical challenges of modern fetal medicine and pediatrics. In recent years several studies have used magnetic resonance imaging (MRI) to demonstrate differences in brain structure in IUGR subjects, but the ability to use MRI for individual predictive purposes in IUGR is limited. Recent research suggests that MRI in vivo access to brain connectivity might have the potential to help understanding cognitive and neurodevelopment processes. Specifically, MRI based connectomics is an emerging approach to extract information from MRI data that exhaustively maps inter-regional connectivity within the brain to build a graph model of its neural circuitry known as brain network. In the present study we used diffusion MRI based connectomics to obtain structural brain networks of a prospective cohort of one year old infants (32 controls and 24 IUGR) and analyze the existence of quantifiable brain reorganization of white matter circuitry in IUGR group by means of global and regional graph theory features of brain networks. Based on global and regional analyses of the brain network topology we demonstrated brain reorganization in IUGR infants at one year of age. Specifically, IUGR infants presented decreased global and local weighted efficiency, and a pattern of altered regional graph theory features. By means of binomial logistic regression, we also demonstrated that connectivity measures were associated with abnormal performance in later neurodevelopmental outcome as measured by Bayley Scale for Infant and Toddler Development, Third edition (BSID-III) at two years of age. These findings show the potential of diffusion MRI based connectomics and graph theory based network characteristics for estimating differences in the architecture of neural circuitry and developing imaging biomarkers of poor neurodevelopment outcome in infants with prenatal diseases. Copyright © 2012 Elsevier Inc. All rights reserved.

Region-Specific Protein Abundance Changes in the Brain of MPTP-induced Parkinson’s Disease Mouse Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Xu; Zhou, Jianying; Chin, Mark H

2010-02-15

Parkinson’s disease (PD) is characterized by dopaminergic neurodegeneration in the nigrostriatal region of the brain; however, the neurodegeneration extends well beyond dopaminergic neurons. To gain a better understanding of the molecular changes relevant to PD, we applied two-dimensional LC-MS/MS to comparatively analyze the proteome changes in four brain regions (striatum, cerebellum, cortex, and the rest of brain) using a MPTP-induced PD mouse model with the objective to identify nigrostriatal-specific and other region-specific protein abundance changes. The combined analyses resulted in the identification of 4,895 non-redundant proteins with at least two unique peptides per protein. The relative abundance changes in eachmore » analyzed brain region were estimated based on the spectral count information. A total of 518 proteins were observed with significant MPTP-induced changes across different brain regions. 270 of these proteins were observed with specific changes occurring either only in the striatum and/or in the rest of the brain region that contains substantia nigra, suggesting that these proteins are associated with the underlying nigrostriatal pathways. Many of the proteins that exhibit significant abundance changes were associated with dopamine signaling, mitochondrial dysfunction, the ubiquitin system, calcium signaling, the oxidative stress response, and apoptosis. A set of proteins with either consistent change across all brain regions or with changes specific to the cortex and cerebellum regions were also detected. One of the interesting proteins is ubiquitin specific protease (USP9X), a deubiquination enzyme involved in the protection of proteins from degradation and promotion of the TGF-β pathway, which exhibited altered abundances in all brain regions. Western blot validation showed similar spatial changes, suggesting that USP9X is potentially associated with neurodegeneration. Together, this study for the first time presents an overall picture of proteome changes underlying both nigrostriatal pathways and other brain regions potentially involved in MPTP-induced neurodegeneration. The observed molecular changes provide a valuable reference resource for future hypothesis-driven functional studies of PD.« less

Phloretin ameliorates 2-chlorohexadecanal-mediated brain microvascular endothelial cell dysfunction in vitro

PubMed Central

Üllen, Andreas; Fauler, Günter; Bernhart, Eva; Nusshold, Christoph; Reicher, Helga; Leis, Hans-Jörg; Malle, Ernst; Sattler, Wolfgang

2012-01-01

2-Chlorohexadecanal (2-ClHDA), a chlorinated fatty aldehyde, is formed via attack on ether-phospholipids by hypochlorous acid (HOCl) that is generated by the myeloperoxidase–hydrogen peroxide–chloride system of activated leukocytes. 2-ClHDA levels are elevated in atherosclerotic lesions, myocardial infarction, and neuroinflammation. Neuroinflammatory conditions are accompanied by accumulation of neutrophils (an ample source of myeloperoxidase) in the brain. Microvessel damage by inflammatory mediators and/or reactive oxidants can induce blood–brain barrier (BBB) dysfunction, a pathological condition leading to cerebral edema, brain hemorrhage, and neuronal death. In this in vitro study we investigated the impact of 2-ClHDA on brain microvascular endothelial cells (BMVEC), which constitute the morphological basis of the BBB. We show that exogenously added 2-ClHDA is subject to rapid uptake and metabolism by BMVEC. Using C16 structural analogues of 2-ClHDA we found that the cytotoxic potential decreases in the following order: 2-ClHDA>hexadecanal>palmitic acid>2-ClHDA-dimethylacetal. 2-ClHDA induces loss of barrier function, mitochondrial dysfunction, apoptosis via activation of caspase 3, and altered intracellular redox balance. Finally we investigated potential protective effects of several natural polyphenols on in vitro BBB function. Of the compounds tested, phloretin almost completely abrogated 2-ClHDA-induced BMVEC barrier dysfunction and cell death. These data suggest that 2-ClHDA has the potential to induce BBB breakdown under inflammatory conditions and that phloretin confers protection in this experimental setting. PMID:22982051

Location of core diagnostic information across various sequences in brain MRI and implications for efficiency of MRI scanner utilization.

PubMed

Sharma, Aseem; Chatterjee, Arindam; Goyal, Manu; Parsons, Matthew S; Bartel, Seth

2015-04-01

Targeting redundancy within MRI can improve its cost-effective utilization. We sought to quantify potential redundancy in our brain MRI protocols. In this retrospective review, we aggregated 207 consecutive adults who underwent brain MRI and reviewed their medical records to document clinical indication, core diagnostic information provided by MRI, and its clinical impact. Contributory imaging abnormalities constituted positive core diagnostic information whereas absence of imaging abnormalities constituted negative core diagnostic information. The senior author selected core sequences deemed sufficient for extraction of core diagnostic information. For validating core sequences selection, four readers assessed the relative ease of extracting core diagnostic information from the core sequences. Potential redundancy was calculated by comparing the average number of core sequences to the average number of sequences obtained. Scanning had been performed using 9.4±2.8 sequences over 37.3±12.3 minutes. Core diagnostic information was deemed extractable from 2.1±1.1 core sequences, with an assumed scanning time of 8.6±4.8 minutes, reflecting a potential redundancy of 74.5%±19.1%. Potential redundancy was least in scans obtained for treatment planning (14.9%±25.7%) and highest in scans obtained for follow-up of benign diseases (81.4%±12.6%). In 97.4% of cases, all four readers considered core diagnostic information to be either easily extractable from core sequences or the ease to be equivalent to that from the entire study. With only one MRI lacking clinical impact (0.48%), overutilization did not seem to contribute to potential redundancy. High potential redundancy that can be targeted for more efficient scanner utilization exists in brain MRI protocols.

The effect of nanoparticle size on the ability to cross the blood-brain barrier: an in vivo study.

PubMed

Betzer, Oshra; Shilo, Malka; Opochinsky, Renana; Barnoy, Eran; Motiei, Menachem; Okun, Eitan; Yadid, Gal; Popovtzer, Rachela

2017-07-01

Our goal was to develop an efficient nanoparticle-based system that can overcome the restrictive mechanism of the blood-brain barrier (BBB) by targeting insulin receptors and would thus enable drug delivery to the brain. Insulin-coated gold nanoparticles (INS-GNPs) were synthesized to serve as a BBB transport system. The effect of nanoparticle size (20, 50 and 70 nm) on their ability to cross the BBB was quantitatively investigated in Balb/C mice. The most widespread biodistribution and highest accumulation within the brain were observed using 20 nm INS-GNPs, 2 h post injection. In vivo CT imaging revealed that particles migrated to specific brain regions, which are involved in neurodegenerative and neuropsychiatric disorders. These findings promote the optimization of nanovehicles for transport of drugs through the BBB. The insulin coating of the particles enabled targeting of specific brain regions, suggesting the potential use of INS-GNPs for delivery of various treatments for brain-related disorders.

Limitations on the developing preterm brain: impact of periventricular white matter lesions on brain connectivity and cognition.

PubMed

Pavlova, Marina A; Krägeloh-Mann, Ingeborg

2013-04-01

Brain lesions to the white matter in peritrigonal regions, periventricular leukomalacia, in children who were born prematurely represent an important model for studying limitations on brain development. The lesional pattern is of early origin and bilateral, that constrains the compensatory potential of the brain. We suggest that (i) topography and severity of periventricular lesions may have a long-term predictive value for cognitive and social capabilities in preterm birth survivors; and (ii) periventricular lesions may impact cognitive and social functions by affecting brain connectivity, and thereby, the dissociable neural networks underpinning these functions. A further pathway to explore is the relationship between cerebral palsy and cognitive outcome. Restrictions caused by motor disability may affect active exploration of surrounding and social participation that may in turn differentially impinge on cognitive development and social cognition. As an outline for future research, we underscore sex differences, as the sex of a preterm newborn may shape the mechanisms by which the developing brain is affected.

Impairment in long-term memory formation and learning-dependent synaptic plasticity in mice lacking glycogen synthase in the brain

PubMed Central

Duran, Jordi; Saez, Isabel; Gruart, Agnès; Guinovart, Joan J; Delgado-García, José M

2013-01-01

Glycogen is the only carbohydrate reserve of the brain, but its overall contribution to brain functions remains unclear. Although it has traditionally been considered as an emergency energetic reservoir, increasing evidence points to a role of glycogen in the normal activity of the brain. To address this long-standing question, we generated a brain-specific Glycogen Synthase knockout (GYS1Nestin-KO) mouse and studied the functional consequences of the lack of glycogen in the brain under alert behaving conditions. These animals showed a significant deficiency in the acquisition of an associative learning task and in the concomitant activity-dependent changes in hippocampal synaptic strength. Long-term potentiation (LTP) evoked in the hippocampal CA3-CA1 synapse was also decreased in behaving GYS1Nestin-KO mice. These results unequivocally show a key role of brain glycogen in the proper acquisition of new motor and cognitive abilities and in the underlying changes in synaptic strength. PMID:23281428

Exosome delivered anticancer drugs across the blood-brain barrier for brain cancer therapy in Danio rerio.

PubMed

Yang, Tianzhi; Martin, Paige; Fogarty, Brittany; Brown, Alison; Schurman, Kayla; Phipps, Roger; Yin, Viravuth P; Lockman, Paul; Bai, Shuhua

2015-06-01

The blood-brain barrier (BBB) essentially restricts therapeutic drugs from entering into the brain. This study tests the hypothesis that brain endothelial cell derived exosomes can deliver anticancer drug across the BBB for the treatment of brain cancer in a zebrafish (Danio rerio) model. Four types of exosomes were isolated from brain cell culture media and characterized by particle size, morphology, total protein, and transmembrane protein markers. Transport mechanism, cell uptake, and cytotoxicity of optimized exosome delivery system were tested. Brain distribution of exosome delivered anticancer drugs was evaluated using transgenic zebrafish TG (fli1: GFP) embryos and efficacies of optimized formations were examined in a xenotransplanted zebrafish model of brain cancer model. Four exosomes in 30-100 diameters showed different morphologies and exosomes derived from brain endothelial cells expressed more CD63 tetraspanins transmembrane proteins. Optimized exosomes increased the uptake of fluorescent marker via receptor mediated endocytosis and cytotoxicity of anticancer drugs in cancer cells. Images of the zebrafish showed exosome delivered anticancer drugs crossed the BBB and entered into the brain. In the brain cancer model, exosome delivered anticancer drugs significantly decreased fluorescent intensity of xenotransplanted cancer cells and tumor growth marker. Brain endothelial cell derived exosomes could be potentially used as a carrier for brain delivery of anticancer drug for the treatment of brain cancer.

The mental cost of cognitive enhancement.

PubMed

Iuculano, Teresa; Cohen Kadosh, Roi

2013-03-06

Noninvasive brain stimulation provides a potential tool for affecting brain functions in the typical and atypical brain and offers in several cases an alternative to pharmaceutical intervention. Some studies have suggested that transcranial electrical stimulation (TES), a form of noninvasive brain stimulation, can also be used to enhance cognitive performance. Critically, research so far has primarily focused on optimizing protocols for effective stimulation, or assessing potential physical side effects of TES while neglecting the possibility of cognitive side effects. We assessed this possibility by targeting the high-level cognitive abilities of learning and automaticity in the mathematical domain. Notably, learning and automaticity represent critical abilities for potential cognitive enhancement in typical and atypical populations. Over 6 d, healthy human adults underwent cognitive training on a new numerical notation while receiving TES to the posterior parietal cortex or the dorsolateral prefrontal cortex. Stimulation to the the posterior parietal cortex facilitated numerical learning, whereas automaticity for the learned material was impaired. In contrast, stimulation to the dorsolateral prefrontal cortex impaired the learning process, whereas automaticity for the learned material was enhanced. The observed double dissociation indicates that cognitive enhancement through TES can occur at the expense of other cognitive functions. These findings have important implications for the future use of enhancement technologies for neurointervention and performance improvement in healthy populations.

Anesthesia, brain changes, and behavior: Insights from neural systems biology.

PubMed

Colon, Elisabeth; Bittner, Edward A; Kussman, Barry; McCann, Mary Ellen; Soriano, Sulpicio; Borsook, David

2017-06-01

Long-term consequences of anesthetic exposure in humans are not well understood. It is possible that alterations in brain function occur beyond the initial anesthetic administration. Research in children and adults has reported cognitive and/or behavioral changes after surgery and general anesthesia that may be short lived in some patients, while in others, such changes may persist. The changes observed in humans are corroborated by a large body of evidence from animal studies that support a role for alterations in neuronal survival (neuroapoptosis) or structure (altered dendritic and glial morphology) and later behavioral deficits at older age after exposure to various anesthetic agents during fetal or early life. The potential of anesthetics to induce long-term alterations in brain function, particularly in vulnerable populations, warrants investigation. In this review, we critically evaluate the available preclinical and clinical data on the developing and aging brain, and in known vulnerable populations to provide insights into potential changes that may affect the general population of patients in a more, subtle manner. In addition this review summarizes underlying processes of how general anesthetics produce changes in the brain at the cellular and systems level and the current understanding underlying mechanisms of anesthetics agents on brain systems. Finally, we present how neuroimaging techniques currently emerge as promising approaches to evaluate and define changes in brain function resulting from anesthesia, both in the short and the long-term. Copyright © 2017 Elsevier Ltd. All rights reserved.

Action of cholinergic poisons on the central nervous system and effectiveness of potential antidotes. Annual report 1 Jul 81-30 Jun 82

DOE Office of Scientific and Technical Information (OSTI.GOV)

Samson, F.; Nelson, S.

The research aim was to determine the effects of soman, related organophosphate toxins and potential antidotes on brain regional functions in rats: The (/sup 14/C)-2-deoxyglucose procedure (2-DG) was used for mapping brain regional glucose use. Quantitative autoradiography was used for muscarinic and nicotinic cholinergic receptors. The 2-DG procedure gives a quantitative measure of glucose utilization in brain regions and is in index of the 'functional activity' in brain regions and systems. Values were determined in controls, rats with soman induced seizures, seizures induced by convulsants (DFP, strychnine, picrotoxin, pentylenetetrazol, penicillin) and soman pretreated with TAB. Brain regional cholinergic receptor mapsmore » were prepared and some regional muscarinic and nicotinic receptor densities have been quantified. Soman (112 micrograms/kg i.m.) causes strong, continuous seizures and a dramatic (2-6 fold) increase in the rate of glucose use in 10 major brain regions. Most intense increases were in septum, substants nigra reticularis and outer layer of hippcampal dendata gyrus. The overt seizures of rats induced by convulsants DFP, strychnine, picrotoxin, pentylenetetrazol and penicillin (in hippocampus) were strikingly different from that of rats with soman seizures. High doses (2X LD50) of soman in rats protected with TAB caused a 50% depression of glucose use in most brain regions. The effects of repeated soman exposure on muscarinic and nicotinic receptors are under study.« less

A Steady-State Visual Evoked Potential Brain-Computer Interface System Evaluation as an In-Vehicle Warning Device

NASA Astrophysics Data System (ADS)

Riyahi, Pouria

This thesis is part of current research at Center for Intelligence Systems Research (CISR) at The George Washington University for developing new in-vehicle warning systems via Brain-Computer Interfaces (BCIs). The purpose of conducting this research is to contribute to the current gap between BCI and in-vehicle safety studies. It is based on the premise that accurate and timely monitoring of human (driver) brain's signal to external stimuli could significantly aide in detection of driver's intentions and development of effective warning systems. The thesis starts with introducing the concept of BCI and its development history while it provides a literature review on the nature of brain signals. The current advancement and increasing demand for commercial and non-medical BCI products are described. In addition, the recent research attempts in transportation safety to study drivers' behavior or responses through brain signals are reviewed. The safety studies, which are focused on employing a reliable and practical BCI system as an in-vehicle assistive device, are also introduced. A major focus of this thesis research has been on the evaluation and development of the signal processing algorithms which can effectively filter and process brain signals when the human subject is subjected to Visual LED (Light Emitting Diodes) stimuli at different frequencies. The stimulated brain generates a voltage potential, referred to as Steady-State Visual Evoked Potential (SSVEP). Therefore, a newly modified analysis algorithm for detecting the brain visual signals is proposed. These algorithms are designed to reach a satisfactory accuracy rate without preliminary trainings, hence focusing on eliminating the need for lengthy training of human subjects. Another important concern is the ability of the algorithms to find correlation of brain signals with external visual stimuli in real-time. The developed analysis models are based on algorithms which are capable of generating results for real-time processing of BCI devices. All of these methods are evaluated through two sets of recorded brain signals which were recorded by g.TEC CO. as an external source and recorded brain signals during our car driving simulator experiments. The final discussion is about how the presence of an SSVEP based warning system could affect drivers' performances which is defined by their reaction distance and Time to Collision (TTC). Three different scenarios with and without warning LEDs were planned to measure the subjects' normal driving behavior and their performance while they use a warning system during their driving task. Finally, warning scenarios are divided into short and long warning periods without and with informing the subjects, respectively. The long warning period scenario attempts to determine the level of drivers' distraction or vigilance during driving. The good outcome of warning scenarios can bridge between vehicle safety studies and online BCI system design research. The preliminary results show some promise of the developed methods for in-vehicle safety systems. However, for any decisive conclusion that considers using a BCI system as a helpful in-vehicle assistive device requires far deeper scrutinizing.

Neuropathology of alcoholism.

PubMed

Sutherland, Greg T; Sheedy, Donna; Kril, Jillian J

2014-01-01

Chronic alcohol consumption results in structural changes to the brain. In alcoholics without coexisting thiamine deficiency or liver disease this is largely restricted to a loss of white-matter volume. When it occurs, neuronal loss is limited in anatomic distribution and only detected with quantitative techniques. This relative paucity of neurodegeneration is reflected in studies of gene and protein expression in postmortem brain where findings are subtle and discordant between studies. In alcoholics with coexisting pathologies, neuronal loss is more marked and affects a wider range of anatomic regions, especially subcortical nuclei. Although this more widespread damage may reflect a more severe drinking history, there is evidence linking thiamine deficiency and the consequences of liver disease to the pathogenesis of alcohol-related brain damage. Furthermore, a range of other factors, such as cigarette smoking and mood disorders, that are common in alcoholics, have the potential to influence studies of brain pathology and should be considered in further studies of the neuropathology of alcoholism. © 2014 Elsevier B.V. All rights reserved.

Two hands, one brain, and aging.

PubMed

Maes, Celine; Gooijers, Jolien; Orban de Xivry, Jean-Jacques; Swinnen, Stephan P; Boisgontier, Matthieu P

2017-04-01

Many activities of daily living require moving both hands in an organized manner in space and time. Therefore, understanding the impact of aging on bimanual coordination is essential for prolonging functional independence and well-being in older adults. Here we investigated the behavioral and neural determinants of bimanual coordination in aging. The studies surveyed in this review reveal that aging is associated with cortical hyper-activity (but also subcortical hypo-activity) during performance of bimanual tasks. In addition to changes in activation in local areas, the interaction between distributed brain areas also exhibits age-related effects, i.e., functional connectivity is increased in the resting brain as well as during task performance. The mechanisms and triggers underlying these functional activation and connectivity changes remain to be investigated. This requires further research investment into the detailed study of interactions between brain structure, function and connectivity. This will also provide the foundation for interventional research programs towards preservation of brain health and behavioral performance by maximizing neuroplasticity potential in older adults. Copyright © 2017 Elsevier Ltd. All rights reserved.

From The Cover: Microtransplantation of functional receptors and channels from the Alzheimer's brain to frog oocytes

NASA Astrophysics Data System (ADS)

Miledi, R.; Dueñas, Z.; Martinez-Torres, A.; Kawas, C. H.; Eusebi, F.

2004-02-01

About a decade ago, cell membranes from the electric organ of Torpedo and from the rat brain were transplanted to frog oocytes, which thus acquired functional Torpedo and rat neurotransmitter receptors. Nevertheless, the great potential that this method has for studying human diseases has remained virtually untapped. Here, we show that cell membranes from the postmortem brains of humans that suffered Alzheimer's disease can be microtransplanted to the plasma membrane of Xenopus oocytes. We show also that these postmortem membranes carry neurotransmitter receptors and voltage-operated channels that are still functional, even after they have been kept frozen for many years. This method provides a new and powerful approach to study directly the functional characteristics and structure of receptors, channels, and other membrane proteins of the Alzheimer's brain. This knowledge may help in understanding the basis of Alzheimer's disease and also help in developing new treatments. -aminobutyric acid receptors | sodium channels | calcium channels | postmortem brain

Different early rearing experiences have long term effects on cortical organization in captive chimpanzees (Pan troglodytes)

PubMed Central

Bogart, Stephanie L.; Bennett, Allyson J.; Schapiro, Steven J.; Reamer, Lisa A.; Hopkins, William D.

2014-01-01

Consequences of rearing history in chimpanzees (Pan troglodytes) have been explored in relation to behavioral abnormalities and cognition, however, little is known about the effects of rearing conditions on anatomical brain development. Human studies have revealed that experiences of maltreatment and neglect during infancy and childhood can have detrimental effects on brain development and cognition. In this study, we evaluated the effects of early rearing experience on brain morphology in 92 captive chimpanzees (ages 11-43) who were either reared by their mothers (n = 46) or in a nursery (n = 46) with age-group peers. Magnetic resonance brain images were analyzed with a processing program (BrainVISA) that extracts cortical sulci. We obtained various measurements from 11 sulci located throughout the brain, as well as whole brain gyrification and white and grey matter volumes. We found that mother-reared chimpanzees have greater global white-to-grey matter volume, more cortical folding and thinner grey matter within the cortical folds than nursery-reared animals. The findings reported here are the first to demonstrate that differences in early rearing conditions have significant consequences on brain morphology in chimpanzees and suggests potential differences in the development of white matter expansion and myelination. PMID:24206013

Different early rearing experiences have long-term effects on cortical organization in captive chimpanzees (Pan troglodytes).

PubMed

Bogart, Stephanie L; Bennett, Allyson J; Schapiro, Steven J; Reamer, Lisa A; Hopkins, William D

2014-03-01

Consequences of rearing history in chimpanzees (Pan troglodytes) have been explored in relation to behavioral abnormalities and cognition; however, little is known about the effects of rearing conditions on anatomical brain development. Human studies have revealed that experiences of maltreatment and neglect during infancy and childhood can have detrimental effects on brain development and cognition. In this study, we evaluated the effects of early rearing experience on brain morphology in 92 captive chimpanzees (ages 11-43) who were either reared by their mothers (n = 46) or in a nursery (n = 46) with age-group peers. Magnetic resonance brain images were analyzed with a processing program (BrainVISA) that extracts cortical sulci. We obtained various measurements from 11 sulci located throughout the brain, as well as whole brain gyrification and white and grey matter volumes. We found that mother-reared chimpanzees have greater global white-to-grey matter volume, more cortical folding and thinner grey matter within the cortical folds than nursery-reared animals. The findings reported here are the first to demonstrate that differences in early rearing conditions have significant consequences on brain morphology in chimpanzees and suggests potential differences in the development of white matter expansion and myelination. © 2013 John Wiley & Sons Ltd.

Effects of tissue optical properties on time-resolved fluorescence measurements from brain tumors: an experimental and computational study

NASA Astrophysics Data System (ADS)

Butte, Pramod V.; Vishwanath, Karthik; Pikul, Brian K.; Mycek, Mary-Ann; Marcu, Laura

2003-07-01

Time-Resolved Laser-Induced Fluorescence Spectroscopy (tr-LIFS) offers the potential for intra-operative diagnosis of primary brain tumors. However, both the intrinsic properties of endogenous fluorophores and the optical properties of brain tissue could affect the fluorescence measurements from brain. Scattering has been demonstrated to increase, for instance, detected lifetimes by 10-20% in media less scattering than the brain. The overall goal of this study is to investigate experimentally and computationally how optical properties of distinct types of brain tissue (normal porcine white and gray matter) affect the propagation of the excitation pulse and fluorescent transients and the detected fluorescence lifetime. A time-domain tr-LIFS apparatus (fast digitizer and gated detection) was employed to measure the propagation of ultra-short pulsed light through brain specimens (1-2.5-mm source-detector separation; 0.100-mm increment). A Monte Carlo model for semi-infinite turbid media was used to simulate time-resolved light propagation for arbitrary source-detector fiber geometries and optical fiber specifications; and to record spatially- and temporally resolved information. We determined a good correlation between experimental and computational results. Our findings provide means for quantification of time-resolved fluorescence spectra from healthy and diseased brain tissue.

Focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor

NASA Astrophysics Data System (ADS)

Chen, Hong; Yang, Georgiana Zong Xin; Getachew, Hoheteberhan; Acosta, Camilo; Sierra Sánchez, Carlos; Konofagou, Elisa E.

2016-06-01

The objective of this study was to unveil the potential mechanism of focused ultrasound (FUS)-enhanced intranasal (IN) brain drug delivery and assess its feasibility in the delivery of therapeutic molecules. Delivery outcomes of fluorescently-labeled dextrans to mouse brains by IN administration either before or after FUS sonication were compared to evaluate whether FUS enhances IN delivery by active pumping or passive diffusion. Fluorescence imaging of brain slices found that IN administration followed by FUS sonication achieved significantly higher delivery than IN administration only, while pre-treatment by FUS sonication followed by IN administration was not significantly different from IN administration only. Brain-derived neurotrophic factor (BDNF), a promising neurotrophic factor for the treatment of many central nervous system diseases, was delivered by IN followed by FUS to demonstrate the feasibility of this technique and compared with the established FUS technique where drugs are injected intravenously. Immunohistochemistry staining of BDNF revealed that FUS-enhanced IN delivery achieved similar locally enhanced delivery as the established FUS technique. This study suggested that FUS enhances IN brain drug delivery by FUS-induced active pumping of the drug and demonstrated that FUS-enhanced IN delivery is a promising technique for noninvasive and localized delivery of therapeutic molecules to the brain.

Identification of Multipotent Stem Cells in Human Brain Tissue Following Stroke.

PubMed

Tatebayashi, Kotaro; Tanaka, Yasue; Nakano-Doi, Akiko; Sakuma, Rika; Kamachi, Saeko; Shirakawa, Manabu; Uchida, Kazutaka; Kageyama, Hiroto; Takagi, Toshinori; Yoshimura, Shinichi; Matsuyama, Tomohiro; Nakagomi, Takayuki

2017-06-01

Perivascular regions of the brain harbor multipotent stem cells. We previously demonstrated that brain pericytes near blood vessels also develop multipotency following experimental ischemia in mice and these ischemia-induced multipotent stem cells (iSCs) can contribute to neurogenesis. However, it is essential to understand the traits of iSCs in the poststroke human brain for possible applications in stem cell-based therapies for stroke patients. In this study, we report for the first time that iSCs can be isolated from the poststroke human brain. Putative iSCs were derived from poststroke brain tissue obtained from elderly stroke patients requiring decompressive craniectomy and partial lobectomy for diffuse cerebral infarction. Immunohistochemistry showed that these iSCs were localized near blood vessels within poststroke areas containing apoptotic/necrotic neurons and expressed both the stem cell marker nestin and several pericytic markers. Isolated iSCs expressed these same markers and demonstrated high proliferative potential without loss of stemness. Furthermore, isolated iSCs expressed other stem cell markers, such as Sox2, c-myc, and Klf4, and differentiated into multiple cells in vitro, including neurons. These results show that iSCs, which are likely brain pericyte derivatives, are present within the poststroke human brain. This study suggests that iSCs can contribute to neural repair in patients with stroke.

Implications of neurovascular uncoupling in functional magnetic resonance imaging (fMRI) of brain tumors.

PubMed

Pak, Rebecca W; Hadjiabadi, Darian H; Senarathna, Janaka; Agarwal, Shruti; Thakor, Nitish V; Pillai, Jay J; Pathak, Arvind P

2017-11-01

Functional magnetic resonance imaging (fMRI) serves as a critical tool for presurgical mapping of eloquent cortex and changes in neurological function in patients diagnosed with brain tumors. However, the blood-oxygen-level-dependent (BOLD) contrast mechanism underlying fMRI assumes that neurovascular coupling remains intact during brain tumor progression, and that measured changes in cerebral blood flow (CBF) are correlated with neuronal function. Recent preclinical and clinical studies have demonstrated that even low-grade brain tumors can exhibit neurovascular uncoupling (NVU), which can confound interpretation of fMRI data. Therefore, to avoid neurosurgical complications, it is crucial to understand the biophysical basis of NVU and its impact on fMRI. Here we review the physiology of the neurovascular unit, how it is remodeled, and functionally altered by brain cancer cells. We first discuss the latest findings about the components of the neurovascular unit. Next, we synthesize results from preclinical and clinical studies to illustrate how brain tumor induced NVU affects fMRI data interpretation. We examine advances in functional imaging methods that permit the clinical evaluation of brain tumors with NVU. Finally, we discuss how the suppression of anomalous tumor blood vessel formation with antiangiogenic therapies can "normalize" the brain tumor vasculature, and potentially restore neurovascular coupling.

Gray matter correlates of creative potential: A latent variable voxel-based morphometry study

PubMed Central

Jauk, Emanuel; Neubauer, Aljoscha C.; Dunst, Beate; Fink, Andreas; Benedek, Mathias

2015-01-01

There is increasing research interest in the structural and functional brain correlates underlying creative potential. Recent investigations found that interindividual differences in creative potential relate to volumetric differences in brain regions belonging to the default mode network, such as the precuneus. Yet, the complex interplay between creative potential, intelligence, and personality traits and their respective neural bases is still under debate. We investigated regional gray matter volume (rGMV) differences that can be associated with creative potential in a heterogeneous sample of N = 135 individuals using voxel-based morphometry (VBM). By means of latent variable modeling and consideration of recent psychometric advancements in creativity research, we sought to disentangle the effects of ideational originality and fluency as two independent indicators of creative potential. Intelligence and openness to experience were considered as common covariates of creative potential. The results confirmed and extended previous research: rGMV in the precuneus was associated with ideational originality, but not with ideational fluency. In addition, we found ideational originality to be correlated with rGMV in the caudate nucleus. The results indicate that the ability to produce original ideas is tied to default-mode as well as dopaminergic structures. These structural brain correlates of ideational originality were apparent throughout the whole range of intellectual ability and thus not moderated by intelligence. In contrast, structural correlates of ideational fluency, a quantitative marker of creative potential, were observed only in lower intelligent individuals in the cuneus/lingual gyrus. PMID:25676914

Formulation and delivery of itraconazole to the brain using a nanolipid carrier system

PubMed Central

Lim, Wei Meng; Rajinikanth, Paruvathanahalli Siddalingam; Mallikarjun, Chitneni; Kang, Yew Beng

2014-01-01

The objectives of this study were to develop and characterize itraconazole (ITZ)-loaded nanostructured lipid carriers (NLCs) and to study their potential for drug delivery into the brain. Precirol® ATO 5 and Transcutol® HP were selected as the lipid phase, and Tween® 80 and Solutol® HS15 as surfactants. The ITZ-NLCs were prepared by a hot and high-pressure homogenization method. The entrapment efficiency for the best formulation batch was analyzed using high-performance liquid chromatography and was found to be 70.5%±0.6%. The average size, zeta potential, and polydispersity index for the ITZ-NLCs used for animal studies were found to be 313.7±15.3 nm, −18.7±0.30 mV, and 0.562±0.070, respectively. Transmission electron microscopy confirmed that ITZ-NLCs were spherical in shape, with a size of less than 200 nm. Differential scanning calorimetry and X-ray diffractometry analysis showed that ITZ was encapsulated in the lipid matrix and present in the amorphous form. The in vitro release study showed that ITZ-NLCs achieved a sustained release, with cumulative release of 80.6%±5.3% up to 24 hours. An in vivo study showed that ITZ-NLCs could increase the ITZ concentration in the brain by almost twofold. These results suggest that ITZ-NLCs can be exploited as nanocarriers to achieve sustained release and brain-targeted delivery. PMID:24833900

The Effects of Exercise on Cognitive Recovery after Acquired Brain Injury in Animal Models: A Systematic Review

PubMed Central

Wogensen, Elise; Malá, Hana

2015-01-01

The objective of the present paper is to review the current status of exercise as a tool to promote cognitive rehabilitation after acquired brain injury (ABI) in animal model-based research. Searches were conducted on the PubMed, Scopus, and psycINFO databases in February 2014. Search strings used were: exercise (and) animal model (or) rodent (or) rat (and) traumatic brain injury (or) cerebral ischemia (or) brain irradiation. Studies were selected if they were (1) in English, (2) used adult animals subjected to acquired brain injury, (3) used exercise as an intervention tool after inflicted injury, (4) used exercise paradigms demanding movement of all extremities, (5) had exercise intervention effects that could be distinguished from other potential intervention effects, and (6) contained at least one measure of cognitive and/or emotional function. Out of 2308 hits, 22 publications fulfilled the criteria. The studies were examined relative to cognitive effects associated with three themes: exercise type (forced or voluntary), timing of exercise (early or late), and dose-related factors (intensity, duration, etc.). The studies indicate that exercise in many cases can promote cognitive recovery after brain injury. However, the optimal parameters to ensure cognitive rehabilitation efficacy still elude us, due to considerable methodological variations between studies. PMID:26509085

Brain tumor recurrence in children treated with growth hormone: the National Cooperative Growth Study experience.

PubMed

Moshang, T; Rundle, A C; Graves, D A; Nickas, J; Johanson, A; Meadows, A

1996-05-01

As of October 1993 the National Cooperative Growth Study included 1262 children with brain tumor who were treated with growth hormone. The type of brain tumor was specified in 947 (75%) of these children. The most common types were glioma, medulloblastoma, and craniopharyngioma, accounting for 91.3% of all those for which type was specified. Brain tumor recurred in 83 (6.6%) of the 1262 children over a total of 6115 patient-years at risk. The frequencies of tumor recurrence in children with low-grade glioma (18.1%), medulloblastoma (7.2%), and craniopharyngioma (6.4%) are lower than those in published reports of tumor recurrence in the general pediatric population with the same types of tumors. The analysis cannot conclusively show that no increased risk of tumor recurrence exists, however, because of the potential incompleteness of data reporting in the National Cooperative Growth Study. Nevertheless the findings are reassuring that children with the more common types of brain tumor who are treated with growth hormone do not seem to be at excessive risk for tumor recurrence.

The Effects of Long-term Abacus Training on Topological Properties of Brain Functional Networks.

PubMed

Weng, Jian; Xie, Ye; Wang, Chunjie; Chen, Feiyan

2017-08-18

Previous studies in the field of abacus-based mental calculation (AMC) training have shown that this training has the potential to enhance a wide variety of cognitive abilities. It can also generate specific changes in brain structure and function. However, there is lack of studies investigating the impact of AMC training on the characteristics of brain networks. In this study, utilizing graph-based network analysis, we compared topological properties of brain functional networks between an AMC group and a matched control group. Relative to the control group, the AMC group exhibited higher nodal degrees in bilateral calcarine sulcus and increased local efficiency in bilateral superior occipital gyrus and right cuneus. The AMC group also showed higher nodal local efficiency in right fusiform gyrus, which was associated with better math ability. However, no relationship was significant in the control group. These findings provide evidence that long-term AMC training may improve information processing efficiency in visual-spatial related regions, which extend our understanding of training plasticity at the brain network level.

Cellular consequences of sleep deprivation in the brain.

PubMed

Cirelli, Chiara

2006-10-01

Several recent studies have used transcriptomics approaches to characterize the molecular correlates of sleep, waking, and sleep deprivation. This analysis may help in understanding the benefits that sleep brings to the brain at the cellular level. The studies are still limited in number and focus on a few brain regions, but some consistent findings are emerging. Sleep, spontaneous wakefulness, short-term, and long-term sleep deprivation are each associated with the upregulation of hundreds of genes in the cerebral cortex and other brain areas. In fruit flies as well as in mammals, three categories of genes are consistently upregulated during waking and short-term sleep deprivation relative to sleep. They include genes involved in energy metabolism, synaptic potentiation, and the response to cellular stress. In the rat cerebral cortex, transcriptional changes associated with prolonged sleep loss differ significantly from those observed during short-term sleep deprivation. However, it is too early to draw firm conclusions relative to the molecular consequences of sleep deprivation, and more extensive studies using DNA and protein arrays are needed in different species and in different brain regions.

Increased risk of brain metastases in women with breast cancer and p16 expression in metastatic lymph-nodes.

PubMed

Furet, Elise; El Bouchtaoui, Morad; Feugeas, Jean-Paul; Miquel, Catherine; Leboeuf, Christophe; Beytout, Clémentine; Bertheau, Philippe; Le Rhun, Emilie; Bonneterre, Jacques; Janin, Anne; Bousquet, Guilhem

2017-06-06

Metastatic breast cancer is a leading cause of mortality in women, partly on account of brain metastases. However, the mechanisms by which cancer cells cross the blood-brain barrier remain undeciphered. Most molecular studies predicting metastatic risk have been performed on primary breast cancer samples. Here we studied metastatic lymph-nodes from patients with breast cancers to identify markers associated with the occurrence of brain metastases. Transcriptomic analyses identified CDKN2A/p16 as a gene potentially associated with brain metastases. Fifty-two patients with HER2-overexpressing or triple-negative breast carcinoma with lymph nodes and distant metastases were included in this study. Transcriptomic analyses were performed on laser-microdissected tumor cells from 28 metastatic lymph-nodes. Supervised analyses compared the transcriptomic profiles of women who developed brain metastases and those who did not. As a validation series, we studied metastatic lymph-nodes from 24 other patients.Immunohistochemistry investigations showed that p16 mean scores were significantly higher in patients with brain metastases than in patients without (7.4 vs. 1.7 respectively, p < 0.01). This result was confirmed on the validation series. Multivariate analyses showed that the p16 score was the only variable positively associated with the risk of brain metastases (p = 0.01).With the same threshold of 5 for p16 scores using a Cox model, overall survival was shorter in women with a p16 score over 5 in both series. The risk of brain metastases in women with HER2-overexpressing or triple-negative breast cancer could be better assessed by studying p16 protein expression on surgically removed axillary lymph-nodes.

Therapeutic Potential of Thymoquinone in Glioblastoma Treatment: Targeting Major Gliomagenesis Signaling Pathways

PubMed Central

Chowdhury, Fabliha Ahmed; Hossain, Md Kamal; Mostofa, A. G. M.; Akbor, Maruf Mohammad

2018-01-01

Glioblastoma multiforme (GBM) is one of the most devastating brain tumors with median survival of one year and presents unique challenges to therapy because of its aggressive behavior. Current treatment strategy involves surgery, radiotherapy, immunotherapy, and adjuvant chemotherapy even though optimal management requires a multidisciplinary approach and knowledge of potential complications from both the disease and its treatment. Thymoquinone (TQ), the main bioactive component of Nigella sativa L., has exhibited anticancer effects in numerous preclinical studies. Due to its multitargeting nature, TQ interferes in a wide range of tumorigenic processes and counteract carcinogenesis, malignant growth, invasion, migration, and angiogenesis. TQ can specifically sensitize tumor cells towards conventional cancer treatments and minimize therapy-associated toxic effects in normal cells. Its potential to enter brain via nasal pathway due to volatile nature of TQ adds another advantage in overcoming blood-brain barrier. In this review, we summarized the potential role of TQ in different signaling pathways in GBM that have undergone treatment with standard therapeutic modalities or with TQ. Altogether, we suggest further comprehensive evaluation of TQ in preclinical and clinical level to delineate its implied utility as novel therapeutics to combat the challenges for the treatment of GBM. PMID:29651429

Real-Time Optical Diagnosis of the Rat Brain Exposed to a Laser-Induced Shock Wave: Observation of Spreading Depolarization, Vasoconstriction and Hypoxemia-Oligemia

PubMed Central

Sato, Shunichi; Kawauchi, Satoko; Okuda, Wataru; Nishidate, Izumi; Nawashiro, Hiroshi; Tsumatori, Gentaro

2014-01-01

Despite many efforts, the pathophysiology and mechanism of blast-induced traumatic brain injury (bTBI) have not yet been elucidated, partially due to the difficulty of real-time diagnosis and extremely complex factors determining the outcome. In this study, we topically applied a laser-induced shock wave (LISW) to the rat brain through the skull, for which real-time measurements of optical diffuse reflectance and electroencephalogram (EEG) were performed. Even under conditions showing no clear changes in systemic physiological parameters, the brain showed a drastic light scattering change accompanied by EEG suppression, which indicated the occurrence of spreading depression, long-lasting hypoxemia and signal change indicating mitochondrial energy impairment. Under the standard LISW conditions examined, hemorrhage and contusion were not apparent in the cortex. To investigate events associated with spreading depression, measurement of direct current (DC) potential, light scattering imaging and stereomicroscopic observation of blood vessels were also conducted for the brain. After LISW application, we observed a distinct negative shift in the DC potential, which temporally coincided with the transit of a light scattering wave, showing the occurrence of spreading depolarization and concomitant change in light scattering. Blood vessels in the brain surface initially showed vasodilatation for 3–4 min, which was followed by long-lasting vasoconstriction, corresponding to hypoxemia. Computer simulation based on the inverse Monte Carlo method showed that hemoglobin oxygen saturation declined to as low as ∼35% in the long-term hypoxemic phase. Overall, we found that topical application of a shock wave to the brain caused spreading depolarization/depression and prolonged severe hypoxemia-oligemia, which might lead to pathological conditions in the brain. Although further study is needed, our findings suggest that spreading depolarization/depression is one of the key events determining the outcome in bTBI. Furthermore, a rat exposed to an LISW(s) can be a reliable laboratory animal model for blast injury research. PMID:24416150

Effects of electroconvulsive seizures on depression-related behavior, memory and neurochemical changes in Wistar and Wistar-Kyoto rats.

PubMed

Kyeremanteng, C; MacKay, J C; James, J S; Kent, P; Cayer, C; Anisman, H; Merali, Z

2014-10-03

Investigations in healthy outbred rat strains have shown a potential role for brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis in the antidepressant and memory side effects of electroconvulsive therapy (ECT, or ECS in animals). The Wistar-Kyoto (WKY) rat strain is used as a genetic model of depression yet no studies to date have directly compared the impact of ECS on the WKY strain to its healthy outbred control (Wistar). The objective of this study is to examine behavioral (antidepressant and retrograde memory) and neurochemical (BDNF and HPA axis) changes immediately (1day) and at a longer delay (7days) after repeated ECS (5 daily administrations) in WKY and Wistar rats. Male Wistar and WKY rats received 5days of repeated ECS or sham treatment and were assessed 1 and 7days later for 1) depression-like behavior and mobility; 2) retrograde memory; and 3) brain BDNF protein, brain corticotropin-releasing factor (CRF) and plasma corticosterone levels. Both strains showed the expected antidepressant response and retrograde memory impairments at 1day following ECS, which were sustained at 7days. In addition, at 1day after ECS, Wistar and WKY rats showed similar elevations in brain BDNF and extra-hypothalamic CRF and no change in plasma corticosterone. At 7days after ECS, Wistar rats showed sustained elevations of brain BDNF and CRF, whereas WKY rats showed a normalization of brain BDNF, despite sustained elevations of brain CRF. The model of 5 daily ECS was effective at eliciting behavioral and neurochemical changes in both strains. A temporal association was observed between brain CRF levels, but not BDNF, and measures of antidepressant effectiveness of ECS and retrograde memory impairments suggesting that extra-hypothalamic CRF may be a potential important contributor to these behavioral effects after repeated ECS/ECT. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of brain lesions on moral agency: ethical dilemmas in investigating moral behavior.

PubMed

Christen, Markus; Müller, Sabine

2015-01-01

Understanding how the "brain produces behavior" is a guiding idea in neuroscience. It is thus of no surprise that establishing an interrelation between brain pathology and antisocial behavior has a long history in brain research. However, interrelating the brain with moral agency--the ability to act in reference to right and wrong--is tricky with respect to therapy and rehabilitation of patients affected by brain lesions. In this contribution, we outline the complexity of the relationship between the brain and moral behavior, and we discuss ethical issues of the neuroscience of ethics and of its clinical consequences. First, we introduce a theory of moral agency and apply it to the issue of behavioral changes caused by brain lesions. Second, we present a typology of brain lesions both with respect to their cause, their temporal development, and the potential for neural plasticity allowing for rehabilitation. We exemplify this scheme with case studies and outline major knowledge gaps that are relevant for clinical practice. Third, we analyze ethical pitfalls when trying to understand the brain-morality relation. In this way, our contribution addresses both researchers in neuroscience of ethics and clinicians who treat patients affected by brain lesions to better understand the complex ethical questions, which are raised by research and therapy of brain lesion patients.

Epidemiology of primary brain tumors: current concepts and review of the literature.

PubMed Central

Wrensch, Margaret; Minn, Yuriko; Chew, Terri; Bondy, Melissa; Berger, Mitchel S.

2002-01-01

The purpose of this review is to provide a sufficiently detailed perspective on epidemiologic studies of primary brain tumors to encourage multidisciplinary etiologic and prognostic studies among surgeons, neuro-oncologists, epidemiologists, and molecular scientists. Molecular tumor markers that predict survival and treatment response are being identified with hope of even greater gains in this area from emerging array technologies. Regarding risk factors, studies of inherited susceptibility and constitutive polymorphisms in genes pertinent to carcinogenesis (for example, DNA repair and detoxification genes and mutagen sensitivity) have revealed provocative findings. Inverse associations of the history of allergies with glioma risk observed in 3 large studies and reports of inverse associations of glioma with common infections suggest a possible role of immune factors in glioma genesis or progression. Studies continue to suggest that brain tumors might result from workplace, dietary, and other personal and residential exposures, but studies of cell phone use and power frequency electromagnetic fields have found little to support a causal connection with brain tumors; caveats remain. The only proven causes of brain tumors (that is, rare hereditary syndromes, therapeutic radiation, and immune suppression giving rise to brain lymphomas) account for a small proportion of cases. Progress in understanding primary brain tumors might result from studies of well-defined histologic and molecular tumor types incorporating assessment of potentially relevant information on subject susceptibility and environmental and noninherited endogenous factors (viruses, radiation, and carcinogenic or protective chemical exposures through diet, workplace, oxidative metabolism, or other sources). Such studies will require the cooperation of researchers from many disciplines. PMID:12356358

Left Brain/Right Brain Learning for Adult Education.

ERIC Educational Resources Information Center

Garvin, Barbara

1986-01-01

Contrasts and compares the theory and practice of adult education as it relates to the issue of right brain/left brain learning. The author stresses the need for a whole-brain approach to teaching and suggests that adult educators, given their philosophical directions, are the perfect potential users of this integrated system. (Editor/CT)

Anatomical connectivity influences both intra- and inter-brain synchronizations.

PubMed

Dumas, Guillaume; Chavez, Mario; Nadel, Jacqueline; Martinerie, Jacques

2012-01-01

Recent development in diffusion spectrum brain imaging combined to functional simulation has the potential to further our understanding of how structure and dynamics are intertwined in the human brain. At the intra-individual scale, neurocomputational models have already started to uncover how the human connectome constrains the coordination of brain activity across distributed brain regions. In parallel, at the inter-individual scale, nascent social neuroscience provides a new dynamical vista of the coupling between two embodied cognitive agents. Using EEG hyperscanning to record simultaneously the brain activities of subjects during their ongoing interaction, we have previously demonstrated that behavioral synchrony correlates with the emergence of inter-brain synchronization. However, the functional meaning of such synchronization remains to be specified. Here, we use a biophysical model to quantify to what extent inter-brain synchronizations are related to the anatomical and functional similarity of the two brains in interaction. Pairs of interacting brains were numerically simulated and compared to real data. Results show a potential dynamical property of the human connectome to facilitate inter-individual synchronizations and thus may partly account for our propensity to generate dynamical couplings with others.

Sodium Channel Voltage-Gated Beta 2 Plays a Vital Role in Brain Aging Associated with Synaptic Plasticity and Expression of COX5A and FGF-2.

PubMed

XiYang, Yan-Bin; Wang, You-Cui; Zhao, Ya; Ru, Jin; Lu, Bing-Tuan; Zhang, Yue-Ning; Wang, Nai-Chao; Hu, Wei-Yan; Liu, Jia; Yang, Jin-Wei; Wang, Zhao-Jun; Hao, Chun-Guang; Feng, Zhong-Tang; Xiao, Zhi-Cheng; Dong, Wei; Quan, Xiong-Zhi; Zhang, Lian-Feng; Wang, Ting-Hua

2016-03-01

The role of sodium channel voltage-gated beta 2 (SCN2B) in brain aging is largely unknown. The present study was therefore designed to determine the role of SCN2B in brain aging by using the senescence-accelerated mice prone 8 (SAMP8), a brain senescence-accelerated animal model, together with the SCN2B transgenic mice. The results showed that SAMP8 exhibited impaired learning and memory functions, assessed by the Morris water maze test, as early as 8 months of age. The messenger RNA (mRNA) and protein expressions of SCN2B were also upregulated in the prefrontal cortex at this age. Treatment with traditional Chinese anti-aging medicine Xueshuangtong (Panax notoginseng saponins, PNS) significantly reversed the SCN2B expressions in the prefrontal cortex, resulting in improved learning and memory. Moreover, SCN2B knockdown transgenic mice were generated and bred to determine the roles of SCN2B in brain senescence. A reduction in the SCN2B level by 60.68% resulted in improvement in the hippocampus-dependent spatial recognition memory and long-term potential (LTP) slope of field excitatory postsynaptic potential (fEPSP), followed by an upregulation of COX5A mRNA levels and downregulation of fibroblast growth factor-2 (FGF-2) mRNA expression. Together, the present findings indicated that SCN2B could play an important role in the aging-related cognitive deterioration, which is associated with the regulations of COX5A and FGF-2. These findings could provide the potential strategy of candidate target to develop antisenescence drugs for the treatment of brain aging.

Detecting number processing and mental calculation in patients with disorders of consciousness using a hybrid brain-computer interface system.

PubMed

Li, Yuanqing; Pan, Jiahui; He, Yanbin; Wang, Fei; Laureys, Steven; Xie, Qiuyou; Yu, Ronghao

2015-12-15

For patients with disorders of consciousness such as coma, a vegetative state or a minimally conscious state, one challenge is to detect and assess the residual cognitive functions in their brains. Number processing and mental calculation are important brain functions but are difficult to detect in patients with disorders of consciousness using motor response-based clinical assessment scales such as the Coma Recovery Scale-Revised due to the patients' motor impairments and inability to provide sufficient motor responses for number- and calculation-based communication. In this study, we presented a hybrid brain-computer interface that combines P300 and steady state visual evoked potentials to detect number processing and mental calculation in Han Chinese patients with disorders of consciousness. Eleven patients with disorders of consciousness who were in a vegetative state (n = 6) or in a minimally conscious state (n = 3) or who emerged from a minimally conscious state (n = 2) participated in the brain-computer interface-based experiment. During the experiment, the patients with disorders of consciousness were instructed to perform three tasks, i.e., number recognition, number comparison, and mental calculation, including addition and subtraction. In each experimental trial, an arithmetic problem was first presented. Next, two number buttons, only one of which was the correct answer to the problem, flickered at different frequencies to evoke steady state visual evoked potentials, while the frames of the two buttons flashed in a random order to evoke P300 potentials. The patients needed to focus on the target number button (the correct answer). Finally, the brain-computer interface system detected P300 and steady state visual evoked potentials to determine the button to which the patients attended, further presenting the results as feedback. Two of the six patients who were in a vegetative state, one of the three patients who were in a minimally conscious state, and the two patients that emerged from a minimally conscious state achieved accuracies significantly greater than the chance level. Furthermore, P300 potentials and steady state visual evoked potentials were observed in the electroencephalography signals from the five patients. Number processing and arithmetic abilities as well as command following were demonstrated in the five patients. Furthermore, our results suggested that through brain-computer interface systems, many cognitive experiments may be conducted in patients with disorders of consciousness, although they cannot provide sufficient behavioral responses.

CircRNAs in the tree shrew (Tupaia belangeri) brain during postnatal development and aging.

PubMed

Lu, CaiXia; Sun, XiaoMei; Li, Na; Wang, WenGuang; Kuang, DeXuan; Tong, PinFen; Han, YuanYuan; Dai, JieJie

2018-04-30

Circular RNAs (circRNAs) are a novel type of non-coding RNA expressed across different species and tissues. At present, little is known about the expression and function of circRNAs in the tree shrew brain. In this study, we used RNA-seq to identify 35,007 circRNAs in hippocampus and cerebellum samples from infant (aged 47-52 days), young (aged 15-18 months), and old (aged 78-86 months) tree shrews. We observed no significant changes in the total circRNA expression profiles in different brain regions over time. However, circRNA tended to be downregulated in the cerebellum over time. Real-time RT-PCR analysis verified the presence of circRNAs. KEGG analysis indicated the occurrence of ubiquitin-mediated proteolysis, the MAPK signaling pathway, phosphatidylinositol signaling system, long-term depression, the rap1 signaling pathway, and long-term potentiation in both brain regions. We also observed that 29,087 (83.1%) tree shrew circRNAs shared homology with human circRNAs. The competing endogenous RNA networks suggested novel_circRNA_007362 potential functions as a 24-miRNAs sponge to regulate UBE4B expression. Thus, we obtained comprehensive circRNA expression profiles in the tree shrew brain during postnatal development and aging, which might help to elucidate the functions of circRNAs during brain aging and in age-related diseases.

Brain Activation Patterns at Exhaustion in Rats That Differ in Inherent Exercise Capacity

PubMed Central

Foley, Teresa E.; Brooks, Leah R.; Gilligan, Lori J.; Burghardt, Paul R.; Koch, Lauren G.; Britton, Steven L.; Fleshner, Monika

2012-01-01

In order to further understand the genetic basis for variation in inherent (untrained) exercise capacity, we examined the brains of 32 male rats selectively bred for high or low running capacity (HCR and LCR, respectively). The aim was to characterize the activation patterns of brain regions potentially involved in differences in inherent running capacity between HCR and LCR. Using quantitative in situ hybridization techniques, we measured messenger ribonuclease (mRNA) levels of c-Fos, a marker of neuronal activation, in the brains of HCR and LCR rats after a single bout of acute treadmill running (7.5–15 minutes, 15° slope, 10 m/min) or after treadmill running to exhaustion (15–51 minutes, 15° slope, initial velocity 10 m/min). During verification of trait differences, HCR rats ran six times farther and three times longer prior to exhaustion than LCR rats. Running to exhaustion significantly increased c-Fos mRNA activation of several brain areas in HCR, but LCR failed to show significant elevations of c-Fos mRNA at exhaustion in the majority of areas examined compared to acutely run controls. Results from these studies suggest that there are differences in central c-Fos mRNA expression, and potential brain activation patterns, between HCR and LCR rats during treadmill running to exhaustion and these differences could be involved in the variation in inherent running capacity between lines. PMID:23028992

Transferrin adsorption onto PLGA nanoparticles governs their interaction with biological systems from blood circulation to brain cancer cells.

PubMed

Chang, Jiang; Paillard, Archibald; Passirani, Catherine; Morille, Marie; Benoit, Jean-Pierre; Betbeder, Didier; Garcion, Emmanuel

2012-06-01

Nanomedicines represent an alternative for the treatment of aggressive glioblastoma tumors. Behaviour of PLGA-nanoparticles (NPs) was here investigated as a function of their protein adsorption characteristics at the different biological interfaces they are expected to face in order to reach brain cancer cells. NPs were studied for size, zeta potential, blood half-life, in vitro endocytic behavior and in vivo accumulation within healthy rat brain and brain tumors. While slightly modifying size (80 to 90 nm) and zeta potential (-44 to -32 mV) protein coating of PLGA-NPs by bovine serum albumin (BSA) or transferrin (Tf) greatly prolonged their blood half-life when intravenously injected in rats and mice. In contrast with THP-1 monocytes, differentiated THP-1 macrophages, F98 glioma cells and astrocytes internalized BSA- and Tf-NPs in vitro. Increase of Tf-NP uptake by F98 cells through caveolae- and clathrin-mediated pathways supports specific interaction between Tf and overexpressed Tf-receptor. Finally, in vivo targeting of healthy brain was found higher with Tf-NPs than with BSA-NPs while both NPs entered massively within brain-developed tumors. Taken together, those data evidence that Tf-NPs represent an interesting nanomedicine to deliver anticancer drugs to glioma cells through systemic or locoregional strategies at early and late tumor stages.

Distribution of lacosamide in the rat brain assessed by in vitro slice technique.

PubMed

Gáll, Zsolt; Vancea, Szende

2018-01-01

Lacosamide is a newer anticonvulsant and is the only one that enhances the slow inactivation of voltage gated sodium channels. It is also claimed to have disease-modifying potential, but its pharmacokinetic properties have been much less discussed in the literature. In rats, lacosamide shows restricted distribution to tissues, and the brain-to-plasma partition coefficient (K p ) is only 0.553. In this study, the brain disposition of lacosamide was evaluated in rat brains, and its neuropharmacokinetic parameters (i.e., protein binding and intracellular accumulation) were assessed using in vitro methods. Brain slice experiments and brain homogenate binding studies were performed for several drugs acting on the central nervous system, and drugs were assayed by using a liquid chromatography-mass spectrometry system. By applying a combined approach, it was found that (1) the unbound volume of distribution in the brain for lacosamide (V u,brain  = 1.37) was lower than that of other classical anticonvulsants; (2) the unbound fraction of lacosamide in the brain (0.899) was slightly lower than its unbound fraction in plasma (0.96); (3) the unbound intracellular-to-extracellular concentration ratio of lacosamide was 1.233, meaning that lacosamide was accumulated in the intracellular space because of its physicochemical properties and zwitterionic structure; and (4) the unbound brain-to-plasma concentration ratio of lacosamide was lower than the total brain-to-plasma concentration ratio (K p,uu,brain  = 0.42 vs. K p  = 0.553). In conclusion, the limited brain distribution of lacosamide is not related to its nonspecific protein-binding capacity; rather, an active transport mechanism across the blood-brain barrier may be involved, which reduces the anticonvulsant and/or antiepileptogenic actions of this drug.

[Determination of irreversibility of clinical brain death. Electroencephalography and evoked potentials].

PubMed

Buchner, H; Ferbert, A

2016-02-01

Principally, in the fourth update of the rules for the procedure to finally determine the irreversible cessation of function of the cerebrum, the cerebellum and the brainstem, the importance of an electroencephalogram (EEG), somatosensory evoked potentials (SEP) and brainstem auditory evoked potentials (BAEP) are confirmed. This paper presents the reliability and validity of the electrophysiological diagnosis, discusses the amendments in the fourth version of the guidelines and introduces the practical application, problems and sources of error.An EEG is the best established supplementary diagnostic method for determining the irreversibility of clinical brain death syndrome. It should be noted that residual brain activity can often persist for many hours after the onset of brain death syndrome, particularly in patients with primary brainstem lesions. The derivation and analysis of an EEG requires a high level of expertise to be able to safely distinguish artefacts from primary brain activity. The registration of EEGs to demonstrate the irreversibility of clinical brain death syndrome is extremely time consuming.The BAEPs can only be used to confirm the irreversibility of brain death syndrome in serial examinations or in the rare cases of a sustained wave I or sustained waves I and II. Very often, an investigation cannot be reliably performed because of existing sound conduction disturbances or failure of all potentials even before the onset of clinical brain death syndrome. This explains why BAEPs are only used in exceptional cases.The SEPs of the median nerve can be very reliably derived, are technically simple and with few sources of error. A serial investigation is not required and the time needed for examination is short. For these reasons SEPs are given preference over EEGs and BAEPs for establishing the irreversibility of clinical brain death syndrome.

The BRAIN Initiative: developing technology to catalyse neuroscience discovery.

PubMed

Jorgenson, Lyric A; Newsome, William T; Anderson, David J; Bargmann, Cornelia I; Brown, Emery N; Deisseroth, Karl; Donoghue, John P; Hudson, Kathy L; Ling, Geoffrey S F; MacLeish, Peter R; Marder, Eve; Normann, Richard A; Sanes, Joshua R; Schnitzer, Mark J; Sejnowski, Terrence J; Tank, David W; Tsien, Roger Y; Ugurbil, Kamil; Wingfield, John C

2015-05-19

The evolution of the field of neuroscience has been propelled by the advent of novel technological capabilities, and the pace at which these capabilities are being developed has accelerated dramatically in the past decade. Capitalizing on this momentum, the United States launched the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative to develop and apply new tools and technologies for revolutionizing our understanding of the brain. In this article, we review the scientific vision for this initiative set forth by the National Institutes of Health and discuss its implications for the future of neuroscience research. Particular emphasis is given to its potential impact on the mapping and study of neural circuits, and how this knowledge will transform our understanding of the complexity of the human brain and its diverse array of behaviours, perceptions, thoughts and emotions.

Bcl-2 upregulation and neuroprotection in guinea pig brain following chronic simvastatin treatment.

PubMed

Franke, Cornelia; Nöldner, Michael; Abdel-Kader, Reham; Johnson-Anuna, Leslie N; Gibson Wood, W; Müller, Walter E; Eckert, Gunter P

2007-02-01

The present study determined if chronic simvastatin administration in vivo would provide neuroprotection in brain cells isolated from guinea pigs after challenge with the Bcl-2 inhibitor HA 14-1 or the NO donor sodium nitroprusside (SNP). Bcl-2 levels were significantly increased in brains of simvastatin-treated guinea pigs while levels of the pro-apoptotic protein Bax were significantly reduced. The ratio of Bax/Bcl-2, being a critical factor of the apoptotic state of cells, was significantly reduced in simvastatin-treated animals. Cholesterol levels in the brain remained unchanged in the simvastatin group. Brain cells isolated from simvastatin-treated guinea pigs were significantly less vulnerable to mitochondrial dysfunction and caspase-activation. These results provide new insight into potential mechanisms for the protective actions of statins within the CNS where programmed cell death has been implicated.