Sulforaphane protects cortical neurons against 5-S-cysteinyl-dopamine-induced toxicity through the activation of ERK1/2, Nrf-2 and the upregulation of detoxification enzymes

The degeneration of dopaminergic neurons in the substantia nigra has been linked to the formation of the endogenous neurotoxin 5-S-cysteinyl-dopamine. Sulforaphane (SFN), an isothiocyanate derived from the corresponding precursor glucosinolate found in cruciferous vegetables has been observed to exert a range of biological activities in various cell populations. In this study, we show that SFN protects primary cortical neurons against 5-S-cysteinyl-dopamine induced neuronal injury. Pre-treatment of cortical neurons with SFN (0.01-1 microM) resulted in protection against 5-S-cysteinyl-dopamine-induced neurotoxicity, which peaked at 100 nM. This protection was observed to be mediated by the ability of SFN to modulate the extracellular signal-regulated kinase 1 and 2 and the activation of Kelch-like ECH-associated protein 1/NF-E2-related factor-2 leading to the increased expression and activity of glutathione-S-transferase (M1, M3 and M5), glutathione reductase, thioredoxin reductase and NAD(P)H oxidoreductase 1. These data suggest that SFN stimulates the NF-E2-related factor-2 pathway of antioxidant gene expression in neurons and may protect against neuronal injury relevant to the aetiology of Parkinson's disease.

Cortical activation during executed, imagined, observed, and passive wrist movements in healthy volunteers and stroke patients

Motor imagery, passive movement, and movement observation have been suggested to activate the sensorimotor system without overt movement. The present study investigated these three covert movement modes together with overt movement in a within-subject design to allow for a fine-grained comparison of their abilities in activating the sensorimotor system, i.e. premotor, primary motor, and somatosensory cortices. For this, 21 healthy volunteers underwent functional magnetic resonance imaging (fMRI). In addition we explored the abilities of the different covert movement modes in activating the sensorimotor system in a pilot study of 5 stroke patients suffering from chronic severe hemiparesis. Results demonstrated that while all covert movement modes activated sensorimotor areas, there were profound differences between modes and between healthy volunteers and patients. In healthy volunteers, the pattern of neural activation in overt execution was best resembled by passive movement, followed by motor imagery, and lastly by movement observation. In patients, attempted overt execution was best resembled by motor imagery, followed by passive movement, and lastly by movement observation. Our results indicate that for severely hemiparetic stroke patients motor imagery may be the preferred way to activate the sensorimotor system without overt behavior. In addition, the clear differences between the covert movement modes point to the need for within-subject comparisons.

Early and late stimulus-evoked cortical hemodynamic responses provide insight into the neurogenic nature of neurovascular coupling

Understanding neurovascular coupling is a prerequisite for the interpretation of results obtained from modern neuroimaging techniques. This study investigated the hemodynamic and neural responses in rat somatosensory cortex elicited by 16 seconds electrical whisker stimuli. Hemodynamics were measured by optical imaging spectroscopy and neural activity by multichannel electrophysiology. Previous studies have suggested that the whisker-evoked hemodynamic response contains two mechanisms, a transient ‘backwards’ dilation of the middle cerebral artery, followed by an increase in blood volume localized to the site of neural activity. To distinguish between the mechanisms responsible for these aspects of the response, we presented whisker stimuli during normocapnia (‘control’), and during a high level of hypercapnia. Hypercapnia was used to ‘predilate’ arteries and thus possibly ‘inhibit’ aspects of the response related to the ‘early’ mechanism. Indeed, hemodynamic data suggested that the transient stimulus-evoked response was absent under hypercapnia. However, evoked neural responses were also altered during hypercapnia and convolution of the neural responses from both the normocapnic and hypercapnic conditions with a canonical impulse response function, suggested that neurovascular coupling was similar in both conditions. Although data did not clearly dissociate early and late vascular responses, they suggest that the neurovascular coupling relationship is neurogenic in origin.

Temporal coupling between stimulus-evoked neural activity and hemodynamic responses from individual cortical columns

Using previously published data from the whisker barrel cortex of anesthetized rodents (Berwick et al 2008 J. Neurophysiol. 99 787–98) we investigated whether highly spatially localized stimulus-evoked cortical hemodynamics responses displayed a linear time-invariant (LTI) relationship with neural activity. Presentation of stimuli to individual whiskers of 2 s and 16 s durations produced hemodynamics and neural activity spatially localized to individual cortical columns. Two-dimensional optical imaging spectroscopy (2D-OIS) measured hemoglobin responses, while multi-laminar electrophysiology recorded neural activity. Hemoglobin responses to 2 s stimuli were deconvolved with underlying evoked neural activity to estimate impulse response functions which were then convolved with neural activity evoked by 16 s stimuli to generate predictions of hemodynamic responses. An LTI system more adequately described the temporal neuro-hemodynamics coupling relationship for these spatially localized sensory stimuli than in previous studies that activated the entire whisker cortex. An inability to predict the magnitude of an initial 'peak' in the total and oxy- hemoglobin responses was alleviated when excluding responses influenced by overlying arterial components. However, this did not improve estimation of the hemodynamic responses return to baseline post-stimulus cessation.

Phenolic acid intake, delivered via moderate champagne wine consumption, improves spatial working memory via the modulation of hippocampal and cortical protein expression/activation.

Aims: While much data exist for the effects of flavonoid-rich foods on spatial memory in rodents, there are no such data for foods/beverages predominantly containing hydroxycinnamates and phenolic acids. To address this, we investigated the effects of moderate Champagne wine intake, which is rich in these components, on spatial memory and related mechanisms relative to the alcohol- and energy-matched controls. Results: In contrast to the isocaloric and alcohol-matched controls, supplementation with Champagne wine (1.78 ml/kg BW, alcohol 12.5% vol.) for 6 weeks led to an improvement in spatial working memory in aged rodents. Targeted protein arrays indicated that these behavioral effects were paralleled by the differential expression of a number of hippocampal and cortical proteins (relative to the isocaloric control group), including those involved in signal transduction, neuroplasticity, apoptosis, and cell cycle regulation. Western immunoblotting confirmed the differential modulation of brain-derived neurotrophic factor, cAMP response-element-binding protein (CREB), p38, dystrophin, 2',3'-cyclic-nucleotide 3'-phosphodiesterase, mammalian target of rapamycin (mTOR), and Bcl-xL in response to Champagne supplementation compared to the control drink, and the modulation of mTOR, Bcl-xL, and CREB in response to alcohol supplementation. Innovation: Our data suggest that smaller phenolics such as gallic acid, protocatechuic acid, tyrosol, caftaric acid, and caffeic acid, in addition to flavonoids, are capable of exerting improvements in spatial memory via the modulation in hippocampal signaling and protein expression. Conclusion: Changes in spatial working memory induced by the Champagne supplementation are linked to the effects of absorbed phenolics on cytoskeletal proteins, neurotrophin expression, and the effects of alcohol on the regulation of apoptotic events in the hippocampus and cortex. Antioxid. Redox Signal. 00, 000-000.

Restrictive feeding practices and adiposity are differentially related to P3b cortical responses to food stimuli in children

Across two studies, we examined the association between adiposity, restrictive feeding practices and cortical processing bias to food stimuli in children. We assessed P3b event-related potential (ERP) during visual oddball tasks in which the frequently presented stimulus was non-food and the infrequently presented stimulus was either a food (Study 1) or non-food (Study 2) item. Children responded to the infrequently presented stimulus and accuracy and speed responses were collected. Restrictive feeding practices, children's height and weight were also measured. In Study 1, the difference in P3b amplitude for infrequently presented food stimuli, relative to frequently presented non-food stimuli, was negatively associated with adiposity and positively associated with restrictive feeding practices after controlling for adiposity. There was no association between P3b amplitude difference and adiposity or restriction in Study 2, suggesting that the effects seen in Study 1 were not due to general attentional processes. Taken together, our results suggest that attentional salience, as indexed by the P3b amplitude, may be important for understanding the neural correlates of adiposity and restrictive feeding practices in children.

Neural population models and cortical field theory: overview

The term neural population models (NPMs) is used here as catchall for a wide range of approaches that have been variously called neural mass models, mean field models, neural field models, bulk models, and so forth. All NPMs attempt to describe the collective action of neural assemblies directly. Some NPMs treat the densely populated tissue of cortex as an excitable medium, leading to spatially continuous cortical field theories (CFTs). An indirect approach would start by modelling individual cells and then would explain the collective action of a group of cells by coupling many individual models together. In contrast, NPMs employ collective state variables, typically defined as averages over the group of cells, in order to describe the population activity directly in a single model. The strength and the weakness of his approach are hence one and the same: simplification by bulk. Is this justified and indeed useful, or does it lead to oversimplification which fails to capture the pheno ...

Cortical hot spots and labyrinths: why cortical neuromodulation for episodic migraine with aura should be personalized

Stimulation protocols for medical devices should be rationally designed. For episodic migraine with aura we outline model-based design strategies toward preventive and acute therapies using stereotactic cortical neuromodulation. To this end, we regard a localized spreading depression (SD) wave segment as a central element in migraine pathophysiology. To describe nucleation and propagation features of the SD wave segment, we define the new concepts of cortical hot spots and labyrinths, respectively. In particular, we firstly focus exclusively on curvature-induced dynamical properties by studying a generic reaction-diffusion model of SD on the folded cortical surface. This surface is described with increasing level of details, including finally personalized simulations using patient's magnetic resonance imaging (MRI) scanner readings. At this stage, the only relevant factor that can modulate nucleation and propagation paths is the Gaussian curvature, which has the advantage of being rather readily accessible by MRI. We conclude with discussing further anatomical factors, such as areal, laminar, and cellular heterogeneity, that in addition to and in relation to Gaussian curvature determine the generalized concept of cortical hot spots and labyrinths as target structures for neuromodulation. Our numerical simulations suggest that these target structures are like fingerprints, they are individual features of each migraine sufferer. The goal in the future will be to provide individualized neural tissue simulations. These simulations should predict the clinical data and therefore can also serve as a test bed for exploring stereotactic cortical neuromodulation.