Search

Objectives: Pyridoxine plays a key role in the development of the human nervous system. Several reports suggest that administration of high doses of pyridoxine can be helpful in improving disturbances such as anxiety and pyridoxine-dependent epilepsy, although it has also been associated with a proconvulsive action. In this study, we investigated in developing rats the effects of repeated administration of various doses of pyridoxine on anxiety-like behavior and the brain excitability-related phenomenon known as cortical spreading depression (CSD). Methods: From postnatal day (P) 7 to P27, Wistar rat pups received per gavage pyridoxine hydrochloride (1 mg/kg/day, or 5 mg/kg/day, or 10 mg/kg/day). On P60-70, the animals were tested in the elevated plus maze (EPM) to evaluate anxiety-like behavior. On P71-80, we recorded the CSD (4-hour recording session). Results: Compared with naïve (gavage-free) and saline-treated controls, pyridoxine-treated groups displayed a significant (p < 0.001) increase in CSD propagation velocity and amplitude of the CSD negative direct-current (DC)-shift, and a decrease in the CSD DC-shift duration. These effects were long-lasting and dose-dependent. In the EPM, no significant pyridoxine-associated effect was observed. Discussion: Our data demonstrate a novel action of pyridoxine on an electrical activity-related phenomenon (CSD) in the developing brain, confirming the hypothesis that the chronic treatment with pyridoxine early in life modulates CSD. Data on CSD propagation suggest that pyridoxine at a high dose might act as a prooxidant agent in the developing brain, a hypothesis that deserves further testing. [ABSTRACT FROM AUTHOR]

The primary visual cortex (V1) is widely used to study brain plasticity, which is not only crucial for normal brain function, such as learning and memory, but also for recovery after brain injuries such as stroke. In standard cage (SC) raised mice, experiencedependent ocular dominance (OD) plasticity in V1 declines with age and is compromised by a lesion in adjacent and distant cortical regions. In contrast, mice raised in an enriched environment (EE), exhibit lifelong OD plasticity and are protected from losing OD plasticity after a stroke-lesion in the somatosensory cortex. Since SC mice with an access to a running wheel (RW) displayed preserved OD plasticity during aging, we investigated whether physical exercise might also provide a plasticity promoting effect after a cortical stroke. To this end, we tested if adult RW-raised mice preserved OD plasticity after stroke and also if short-term running after stroke restored OD plasticity to SC mice. Indeed, unlike mice without a RW, adult RW mice continued to show OD plasticity even after stroke, and a 2 weeks RW experience after stroke already restored lost OD plasticity. Additionally, the experience-enabled increase of the spatial frequency and contrast threshold of the optomotor reflex of the open eye, normally lost after a stroke, was restored in both groups of RWmice. Our data suggest that physical exercise alone can not only preserve visual plasticity into old age, but also restore it after a cortical stroke. [ABSTRACT FROM AUTHOR]

Age-related decline in gray and white brain matter goes together with cognitive depletion. To influence cognitive functioning in elderly, several types of physical exercise and nutritional intervention have been performed. This paper systematically reviews the potential additive and complementary effects of nutrition/nutritional supplements and physical exercise on cognition. The search strategy was developed for EMBASE, Medline, PubMed, Cochrane, CINAHL, and PsycInfo databases and focused on the research question: "Is the combination of physical exercise with nutrition/nutritional supplementation more effective than nutrition/nutritional supplementation or physical exercise alone in effecting on brain structure, metabolism, and/or function?" Both mammalian and human studies were included. In humans, randomized controlled trials that evaluated the effects of nutrition/nutritional supplements and physical exercise on cognitive functioning and associated parameters in healthy elderly (>65 years) were included. The systematic search included English and German language literature without any limitation of publication date. The search strategy yielded a total of 3129 references of which 67 studies met the inclusion criteria; 43 human and 24 mammalian, mainly rodent, studies. Three out of 43 human studies investigated a nutrition/physical exercise combination and reported no additive effects. In rodent studies, additive effects were found for docosahexaenoic acid supplementation when combined with physical exercise. Although feasible combinations of physical exercise/nutritional supplements are available for influencing the brain, only a few studies evaluated which possible combinations of nutrition/nutritional supplementation and physical exercise might have an effect on brain structure, metabolism and/or function. The reason for no clear effects of combinatory approaches in humans might be explained by the misfit between the combinations of nutritional methods with the physical interventions in the sense that they were not selected on sharing of similar neuronal mechanisms. Based on the results from this systematic review, future human studies should focus on the combined effect of docosahexaenoic acid supplementation and physical exercise that contains elements of (motor) learning. [ABSTRACT FROM AUTHOR]

The author reflects on the cerebral endothelial and glial cells which acts as blood-brain barrier (BBB). Topics discussed include malfunction of BBB caused by brain milieu, prevalence of cerebrovascular diseases, and role played by microglia and macrophages in BBB. Also mentioned are xenobiotic-metabolizing enzymes, oxidative stress response, and neuroinflammation.

Undernutrition is characterized by an imbalance of essential nutrients with an insufficient nutritional intake, a disorder in which the clinical manifestations in most cases are the result of the economic and social context in which the individual lives. In 1990, the study by the medical and humanitarian Naíde Teodósio (1915-2005) and coworkers, which formulated the Regional Basic Diet (RBD) model for inducing undernutrition, was published. This diet model took its origin from the observation of the dietary habits of families that inhabited impoverished areas from the Pernambuco State. RBD mimics an undernutrition framework that extends not only to the Brazilian population, but to populations in different regions worldwide. The studies based on RBD-induced deficiencies provide a better understanding of the impact of undernutrition on the pathophysiological mechanisms underlying the most diverse prevalent diseases. Indexed papers that are analyzed in this review focus on the importance of using RBD in different areas of knowledge. These papers reflect a new paradigm in translational medicine: they show how the study of pathology using the RBD model in animals over the past 30 years has and still can help scientists today, shedding light on the mechanisms of prevalent diseases that affect impoverished populations.

The goat milk contains conjugated linoleic acid (CLA), which can influence physical growth and brain development. This study investigated the impact of a diet containing goat milk fat (GMF) on physical parameters of gestating (G) and/or lactating (L) rat dams, and their progeny's physical growth, and anxiety behavior. In the dams, body weight was evaluated during gestation and lactation. Maternal physical parameters, thoracic and abdominal circumference and liver weight were measured at weaning. In the progeny, indicators of somatic development, and consolidation of reflex responses (palm grasp, righting, free-fall righting, vibrissa placing, auditory startle response, negative geotaxis and cliff avoidance) were determined. Anxiety behavior was tested on the elevated plus maze (EPM). Compared to the controls, GMF-pups presented higher body weight and tail length at days 18 and 21 (groups G+L and L). In the L-group, cliff avoidance and free-fall righting responses were respectively delayed, and accelerated. Fur appearance was anticipated in G+L pups. On postnatal day 35, the EPM responses of the G group indicated less anxiety than in the controls. Data show developmental and behavioral modifications in the progeny of dams fed the GMF-rich diet consumed during gestation and lactation, suggesting the involvement of CLA in such effects., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Conjugated linoleic acids (CLA) are fatty acids that are found in the lipids from goat milk, and appear to protect neurons from excitotoxicity., Methods: We investigated in developing rats the effects of a maternal CLA-rich diet (containing 7% lipids from goat milk) on body development and cerebral electrical activity of the progeny from dams receiving the CLA diet during gestation (G), lactation (L) or both periods (G+L)., Results: Compared to a control group (C) receiving a diet with 7% soybean oil, body weight increased at 14, 21 and 28 days, but not at 35-45 days, in L and G+L groups (P<0.05). No intergroup difference was found on body and brain weights, body length, abdominal and thoracic circumferences, body mass index and abdominal to thoracic circumference ratio at 35-45 days. In contrast, at this later age the CSD velocities of propagation were significantly higher (P<0.05) in L as compared with the C and G group, and in the L+G, as compared with the C, G and L groups, suggesting a long-lasting brain effect., Conclusion: These data indicate that a maternal CLA-rich diet can differentially influence body weight increment (short-term effect), and CSD propagation (long-term effect) in the progeny, and the lactation is the most critical period for such diet actions., General Significance: The facilitating effect of the lipids from goat milk on an excitability-related phenomenon in the brain (CSD) can be of clinical relevance, since CSD has been associated to neurological disturbances like migraine and epilepsy., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Ascorbic acid (AA) is an antioxidant molecule that is highly concentrated in the brain and can exert both anticonvulsant and proconvulsant effects in distinct models of experimental seizures. Herein, we investigated whether chronic AA administration alters cortical excitability as indexed by the cortical spreading depression (CSD). Well-nourished (W) and malnourished (M) rats were treated, by gavage, with 60mg/kg/day of l-AA from postnatal days 7-28, and CSD propagation was analyzed at 30-40 days. Compared to the W groups, M rats presented higher (p<0.05) CSD amplitudes and velocities of propagation. In both nutritional conditions, AA-treatment significantly increased CSD amplitudes and propagation velocities (p<0.05), as compared to non-treated ('naïve'; Nv) and saline-treated (Sal) controls. The mean±standard deviation CSD velocities of propagation (in mm/min) for the Sal, AA and Nv groups were respectively 3.75±0.03, 4.26±0.08 and 3.81±0.04 for the W condition and 4.29±0.08, 4.51±0.04 and 4.30±0.04 for the M groups. The results demonstrate a CSD-facilitation by AA regardless of nutritional status. They also suggest that, at the dose of 60mg/kg/day chronically administered during brain development, AA may act as a prooxidant in brain, in view of the contrasting effect as compared with other antioxidants, which reduce CSD., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

We have recently shown that two techniques of brain stimulation - repetitive electrical stimulation (ES) (that mimics transcranial magnetic stimulation) and transcranial direct current stimulation (tDCS) - modify the velocity of cortical spreading depression (CSD) significantly. Herein we aimed to study the effects of these two techniques combined on CSD. Thirty-two Wistar rats were divided into four groups according to the treatment: sham tDCS/sham ES, sham tDCS/1 Hz ES, anodal tDCS/1 Hz ES, cathodal tDCS/1 Hz ES. Our findings show that 1 Hz ES reduced CSD velocity, and this effect was modified by either anodal or cathodal tDCS. Anodal tDCS induced larger effects than cathodal tDCS. Hereby CSD velocity was actually increased significantly after anodal tDCS/1 Hz ES. Our results show that combining two techniques of brain stimulation can modify significantly the effects of ES alone on cortical excitability as measured by the neurophysiological parameter of cortical spreading depression and therefore provide important insights into the effects of this new approach of brain stimulation on cortical activity.

Abnormal cortical excitability influences susceptibility to cortical spreading depression (CSD) in migraine. Because transcranial direct current stimulation (tDCS) is capable of inducing lasting changes of cortical excitability, we investigated the after-effects of tDCS on the propagation velocity of CSD in the rat. Twenty-five anesthetised rats received either anodal, cathodal or sham tDCS. The stimulation was applied for 20 min at a current strength of 200 microA after the recording of three baseline CSD measurements. Starting 5 min after tDCS, a further three CSDs were elicited and CSD velocity recorded at intervals of 20 min. tDCS and CSD recording was performed under anaesthesia with chloralose and urethane. As compared to the baseline velocity of 3.14 mm/min, anodal tDCS induced a significant increase of propagation velocity during the first post-tDCS recording (3.49 mm/min). In contrast to anodal tDCS, neither cathodal tDCS nor sham tDCS, which consisted of an initial ramped DC stimulation lasting only 20 s, showed a significant effect on CSD propagation velocity. As anodal tDCS is known to induce a lasting increase of cortical excitability in the clinical setting, our results support the notion that CSD propagation velocity reflects cortical excitability. Since cortical excitability and susceptibility to CSD is elevated in migraine patients, anodal tDCS - by increasing cortical excitability - might increase the probability of migraine attack in these patients, even beyond the end of its application.

This study investigated the effects of repeated l-arginine administration during lactation, combined with different suckling conditions, on morphometric parameters of primary visual cortex NADPH-diaphorase-positive neurons. Wistar rat pups reared in "normal-size litters" or "large litters" (N- and L-conditions; litters formed by 6 and 12 pups, respectively) received, from postnatal day 7 to 28, either arginine (300 mg/kg/day, per gavage) or distilled water (control). At 90-120 days of life, they were perfused with saline + formaldehyde, and their brains were processed for histochemical reaction to reveal NADPH-diaphorase-positive neurons (malic enzyme indirect method). Compared to the normal-size litters, L-rats had lower body weights (P < 0.05), confirming the effectiveness of the L-condition in affecting pup development. Concerning NADPH-d histochemistry, arginine treatment was associated with increased (P < 0.05) density of dendrite varicosities and of dendrite branching frequency, suggesting a plastic response of the developing brain to that treatment, even in previously malnourished rats. No difference was seen, however, in dendrite orientation, total number of neurons, soma area and perimeter, as well as dendrite bifurcation points, fractal dimension, and area and volume of dendrite field, suggesting that NADPH-d cells are resistant to arginine and nutritional changes, regarding these features. Data are considered of interest for studies of synaptic plasticity during neural development and its relationships to aggressive agents like malnutrition.