Asymmetry in the dopamine content in the nucleus accumbens and the motor preference in rats

A number of published studies reported a correlation between the paw preference in mice and asymmetry of tissue concentrations of dopamine (DA) and DA metabolites measured in the nucleus accumbens (NAcb) the DA concentration being higher in the nucleus ipsylateral to a preferred paw. This study aimed to investigate whether such asymmetry existed in rats. The paw preference was defined by reaching into a small horizontal tube for a food pellet. Tissue concentration of DA was measured by high-performance liquid chromatography with electrochemical detection. It was shown that the DA concentration in the left NAcb was significantly higher in "left-handed" rats than in "right-handed" animals. Within the group of "right-handers", the DA concentration was significantly higher in the right NAcb than in the left NAcb. The results confirm in part the experimental data obtained in mice and support the hypothesis that the paw preference is paralleled by elevated tissue DA in the ipsylateral NAcb of rodents.     

Sexual differences in certain forms of motor asymmetry in rats

Using three tests, studies have been made on locomotor lateralization in Wistar rats. It was shown that rat prefer the left paw for obtaining food from a tube, this preference being more pronounced in females. Females are more asymmetric also in preference of a side turn in a labyrinth: they choose the right side. In males, the preference of the right and left turns, as well as the absence of locomotor asymmetry were almost equal. These data are rather similar to those obtained for human subjects. Studies on the direction of rotation of rats after apomorphine injections did not reveal any sex differences or populational preferences.     

Lateralization of catecholaminergic and behavioral response to cerebral infarction in the rat.

The effects of left middle cerebral artery ligation on brain catecholamine concentrations and behavior were compared with those effects of right middle cerebral artery ligation which have previously been reported. Although the lesion caused by middle cerebral artery ligation appeared to be identical on the two sides, the animals with left hemispheric lesion showed no postoperative change in either mean spontaneous 24 hour activity or mean catecholamine concentrations in several areas of the brain. In marked contrast, as we have previously reported and was confirmed in the present study, the animals with a right hemispheric infarct are hyperactive for about 2 to 3 weeks after surgery and there is a significant decrease in mean norepinephrine concentrations in several brain regions. These studies have demonstrated a remarkable asymmetry in the behavioral and biochemical response to cerebral cortical infarction. It is uncertain whether this asymmetry reflects an underlying hemispheric difference in catecholaminergic or non-catecholaminergic neurons.     

The relationship of callosal anatomy to paw preference in dogs

Previous studies have described the paw preference and asymmetry in dog brains, based on experimental studies. The purpose of the present study is to investigate a possible association between callosal anatomy and paw preference in dogs. The midsagittal area of the dog corpus callosum was measured in its entirety and in six subdivisions in a sample of 21 brains obtained from 9 male and 12 female mongrel dogs which had paw preference testing. The present study showed significant paw differences in dog corpus callosum. A posterior segment of the callosum, the isthmus, was significantly larger in the right pawedness than the left.     

Evolutionary and developmental implications of asymmetric brain folding in a large primate pedigree

Bilateral symmetry is a fundamental property of the vertebrate central nervous system. Local deviations from symmetry provide various types of information about the development, evolution, and function of elements within the CNS, especially the cerebral hemispheres. Here, we quantify the pattern and extent of asymmetry in cortical folding within the cerebrum of Papio baboons and assess the evolutionary and developmental implications of the findings. Analyses of directional asymmetry show a population‐level trend in length measurements indicating that baboons are genetically predisposed to be asymmetrical, with the right side longer than the left in the anterior cerebrum while the left side is longer than the right posteriorly. We also find a corresponding bias to display a right frontal petalia (overgrowth of the anterior pole of the cerebral cortex on the right side). By quantifying fluctuating asymmetry, we assess canalization of brain features and the susceptibility of the baboon brain to developmental perturbations. We find that features are differentially canalized depending on their ontogenetic timing. We further deduce that development of the two hemispheres is to some degree independent. This independence has important implications for the evolution of cerebral hemispheres and their separate specialization. Asymmetry is a major feature of primate brains and is characteristic of both brain structure and function.     

MiR-539 Targets MMP-9 to Regulate the Permeability of Blood–Brain Barrier in Ischemia/Reperfusion Injury of Brain

Cerebral ischemia/reperfusion (I/R) injury severely threatens human life, while the potential mechanism underlying it is still need further exploration. The rat model of cerebral I/R injury was established using middle cerebral artery occlusion (MCAO). The rat microvascular endothelial cell line bEND.3 was exposed to oxygen–glucose deprivation/reperfusion (OGD/R) to mimic ischemic condition in vitro. Evans blue was performed to determine the blood–brain barrier (BBB) permeability. Real-time PCR and western blot were performed to determine gene expression in mRNA and protein level, individually. Luciferase reporter assay was conducted to determine the relationship between miR-539 and MMP-9. The infarct volume and BBB permeability of cerebral (I/R) rats were significantly greater than Sham group. The expression of miR-539 was decreased, while MMP-9 was increased in the brain tissues of I/R injury rats and OGD/R pretreated bEND.3. Up-regulated miR-539 in OGD/R pretreated bEND.3 significantly promoted the BBB permeability. MiR-539 targets MMP-9 to regulate its expression. OGD/R treatment significantly promoted the BBB permeability in bEND.3, miR-539 mimic transfection abolished the effects of OGD/R, while co-transfected with pcDNA-MMP-9 abolished the effects of miR-539 mimic. MiR-539 targets MMP-9 and further regulates the BBB permeability in cerebral I/R injury.     

The role of individual characteristics and learning in the manifestation of motor asymmetry in rats

Relative role was studied of the "initial" preference (caused by animals individual properties) and learning in real preference of one limb in rats. After a short-time learning to get food from a narrow horizontal pipe only by the left paw a retrograde amnesia was evoked in rats. At preference determination after three weeks, in conditions which allowed to get food by any paw, in the group of animals without amnesia the number of the left-handed rats was 5.7 times more than of the right-handed ones. In the group of animals with amnesia the numbers of the left-handed, right-handed and ambidextrous were approximately equal. Correlation was revealed between the speed of learning to get food by the left paw and the number of attempts to use the right paw. It has been shown that the initial preference may be stably changed even by a short-time learning (3 food seizures). By the degree of manifestation of the initial preference the rats form a continuum with a gradual transition from pronounced right-handed animals to pronounced left-handed ones. The weaker is the initial preference, the greater the role of learning in the real preference of one of the paws.     

Asymmetry in East African skulls

Skulls from 297 East Africans were examined in relation to their symmetry; 98% were found to be asymmetrical. The most common types of asymmetry were right fronto-petalia, left parieto-petalia, and left occipito-petalia (21.2%). No significant differences were found among the East African populations. Sixteen per cent of the skulls had wormian bones, all of which were found in asymmetrical skulls. The problem of asymmetry of skulls is discussed and the literature on the subject reviewed.     

Blood-brain barrier tight junctions are altered during a 72-h exposure to lambda-carrageenan-induced inflammatory pain

In this study, we examined the effect of lambda-carrageenan-induced inflammatory pain on the functional and structural properties of the rat blood-brain barrier (BBB) over a 72-h time period. Systemic inflammation was induced by an intraplantar injection of 3% lambda-carrageenan into the right hind paw of female Sprague-Dawley rats. In situ brain perfusion and Western blot analyses were performed at 1, 3, 6, 12, 24, 48, and 72 h. In situ brain perfusion showed lambda-carrageenan significantly increased brain uptake of [(14)C]sucrose at 1, 3, 6, and 48 h (139 +/- 9%, 166 +/- 19%, 138 +/- 13%, and 146 +/- 7% compared with control, respectively). Capillary depletion analysis insured the increased brain uptake was due to increased BBB permeability and not vascular trapping. Western blot analyses for zonula occludens-1 (ZO-1) and occludin were performed on isolated cerebral microvessels. ZO-1 expression was significantly increased at 1, 3, and 6 h and returned to control expression levels by 12 h. Total occludin expression was significantly reduced at 1, 3, 6, 12, and 48 h. This investigation demonstrated that lambda-carrageenan-induced inflammatory pain elicits a biphasic increase in BBB permeability with the first phase occurring from 1-6 h and the second phase occuring at 48 h. Furthermore, changes in BBB function are correlated with altered tight junctional protein expression of occludin and ZO-1. Changes in the structure of tight junctions may have important clinical ramifications concerning central nervous system homeostasis and therapeutic drug delivery.     

All-Trans Retinoic Acid Ameliorates the Early Experimental Cerebral Ischemia–Reperfusion Injury in Rats by Inhibiting the Loss of the Blood–Brain Barrier via the JNK/P38MAPK Signaling Pathway

All-trans retinoic acid (ATRA) influences the outcomes of cerebral ischemic reperfusion (CIR) injury, but the mechanism remains unclear. The present study aimed to investigate the effects of ATRA on loss of the blood brain barrier (BBB) following CIR and to explore the possible mechanisms. Transient middle cerebral artery occlusion was performed on male SD rats to construct an in vivo CIR model. Neurological deficits, BBB permeability, brain edema, MRI and JNK/P38 MAPK proteins were detected at 24 h following CIR. We demonstrated that ATRA pretreatment could alleviate CIR-induced neurological deficits, increase of BBB permeability, infarct volume, degradation of tight junction proteins, inhibit MMP-9 protein expression and activity. ATRA treatment also reduced the p-P38 and p-JNK protein level. However the protective effect of ATRA on CIR could be reversed by administration of retinoic acid alpha receptor antagonist Ro41-5253. SP600125 and SB203580, which is the JNK/P38 pathway inhibitors has the same protective effect as ATRA. These results indicated that ATRA may inhibit the JNK/P38 MAPK pathway to alleviate BBB disruption and improve CIR outcomes.     

Aging and sex influence the permeability of the blood-brain barrier in the rat

The aim of the present study was to investigate the existence of aging- and sex-related alterations in the permeability of the blood-brain barrier (BBB) in the rat, by calculating a unidirectional blood-to-brain transfer constant (Ki) for the circulating tracer [14C]-alpha-aminoisobutyric acid. We observed that: a) the permeability of the BBB significantly increased within the frontal and temporo-parietal cortex, hypothalamus and cerebellum in 28-30 week old rats, in comparison with younger animals; b) in several brain areas of female intact rats higher Ki values (even though not significantly different) were calculated at oestrus than at proestrus; c) in 1-week ovariectomized rats there was a marked increase of Ki values at the level of the frontal, temporo-parietal and occipital cortex, cerebellum and brain-stem. One can speculate that aging- and sex-related alterations in the permeability of the BBB reflect respectively changes in brain neurochemical system activity and in plasma steroid hormone levels.     

Calcitonin gene-related peptide prevents blood-brain barrier injury and brain edema induced by focal cerebral ischemia reperfusion

Cerebral ischemia is one of the diseases that most compromise the human species. Therapeutic recovery of blood-brain barrier (BBB) disruption represents a novel promising approach to reduce brain injury after stroke. To determine the effects of calcitonin gene-related peptide (CGRP) on the BBB participate in stroke progression, rat cerebral ischemia reperfusion injury was induced by a 2-hour left transient middle cerebral artery occlusion (MCAO) using an intraluminal filament, followed by 46h of reperfusion. CGRP (1μg/ml) at the dose of 3μg/kg (i.p.) was administered at the beginning of reperfusion. Subsequently, 48h after MCAO, arterial blood pressure, infarct volume, water content, BBB permeability, BBB ultrastructure, levels of aquaporin-4 (AQP4) and its mRNA were evaluated. CGRP could reduce arterial blood pressure (P<0.001), infarct volume (P<0.05), cerebral edema (P<0.01), BBB permeability (P<0.05), AQP4 mRNA expression (P<0.05) and AQP4 protein expression (P<0.01). Furthermore, CGRP treatment improved ultrastructural damage of capillary endothelium cells and decreased the loss of the tight junction observed by transmission electronic microscopy (TEM) after 46h of reperfusion. Our findings show that CGRP significantly reduced postischemic increase of brain edema with a 2-hour therapeutic window in the transient model of focal cerebral ischemia. Moreover, it seems that at least part of the anti-edematous effects of CGRP is due to decrease of BBB disruption by improving ultrastructural damage of capillary endothelium cells, enhancing basal membrane, and inhibiting AQP4 and its mRNA over-expression. The data of the present study provide a new possible approach for acute stroke therapy by administration of CGRP.     

Significance of the corpus callosum in the paired activity of the respiratory center

The asymmetrical reactions of respiratory neurons of the right and left halves of the respiratory center and varied changes in bioelectrical activity of external intercostal muscles on both sides of the chest were discovered in experiments on anesthetized cats in response to successive electrical stimulation of the symmetrical cortical areas of the right and left cerebral hemispheres before and after callosotomy. It was demonstrated that callosotomy increased on both sides of the respiratory center the quantity of neurons responsive to ipsilateral cortical stimulation and determined the character of the asymmetrical reactions of right and left respiratory neurons and intercostal muscles. On the basis of the data obtained it is concluded that the corpus callosum contributes to the functional integration of both halves of the respiratory center.     

Gender differences in medium-latency acoustic evoked potentials

Medium-latency acoustic (auditory) evoked potentials (MLAEPs) were recorded in 30 men and 30 women. The MLAEPs recorded in the left and right mastoid derivations were found to be asymmetrical, the lateral differences depending on the sex: binaural stimulation and stimulation of the right ear yielded a higher total amplitude of the set of medium-latency components in the right derivation in men and in the left derivation in women. If the left ear was stimulated, there were no sex-related differences in MLAEP asymmetry. The data are discussed in terms of gender differences with respect to functional specialization of the cerebral hemispheres.     

Sufficient virus-neutralizing antibody in the central nerve system improves the survival of rabid rats

Background

Rabies is known to be lethal in human. Treatment with passive immunity for the rabies is effective only when the patients have not shown the central nerve system (CNS) signs. The blood–brain barrier (BBB) is a complex functional barrier that may compromise the therapeutic development in neurological diseases. The goal of this study is to determine the change of BBB integrity and to assess the therapeutic possibility of enhancing BBB permeability combined with passive immunity in the late stage of rabies virus infection.

Methods

The integrity of BBB permeability in rats was measured by quantitative ELISA for total IgG and albumin levels in the cerebrospinal fluid (CSF) and by exogenously applying Evans blue as a tracer. Western blotting of occludin and ZO-1, two tight junction proteins, was used to assess the molecular change of BBB structure.The breakdown of BBB with hypertonic arabinose, recombinant tumor necrosis factor-alpha (rTNF-γ), and focused ultrasound (FUS) were used to compare the extent of BBB disruption with rabies virus infection. Specific humoral immunity was analyzed by immunofluorescent assay and rapid fluorescent focus inhibition test. Virus-neutralizing monoclonal antibody (mAb) 8-10E was administered to rats with hypertonic breakdown of BBB as a passive immunotherapy to prevent the death from rabies.

Results

The BBB permeability was altered on day 7 post-infection. Increased BBB permeability induced by rabies virus infection was observed primarily in the cerebellum and spinal cord. Occludin was significantly decreased in both the cerebral cortex and cerebellum. The rabies virus-specific antibody was not strongly elicited even in the presence of clinical signs. Disruption of BBB had no direct association with the lethal outcome of rabies. Passive immunotherapy with virus-neutralizing mAb 8-10E with the hypertonic breakdown of BBB prolonged the survival of rabies virus-infected rats.

Conclusions

We demonstrated that the BBB permeability was altered in a rat model with rabies virus inoculation. Delivery of neutralizing mAb to the infected site in brain combined with effective breakdown of BBB could be an aggressive but feasible therapeutic mode in rabies when the CNS infection has been established.     

Hemispheric participation in the shaping of spatial-motor asymmetry in visual recognition in rats

Asymmetry of movement direction was found in Wistar rats at establishing of motor alimentary conditioned reflex to simultaneously presented visual stimuli. In the course of learning the asymmetry weakened on the whole, but some individuals retained right- or left side preference. The analysis of asymmetry change before and after unilateral cortical inactivation revealed a special role of right hemisphere influences for the formation of right-side preference and of the left hemisphere--for the choice of the left direction. The lack of asymmetry was observed at the presence of the influences from the left hemisphere cortex depressing ipsilateral nigro-striate system and activating the contralateral one. Influences of the cortex of both hemispheres reduce the absolute value of the asymmetry coefficient; the left hemisphere has a special significance for manifestation of temporal asymmetry parameters. Photic interference is a factor modulating the asymmetry. It reduces the right hemisphere activity more than that of the left one; it intensifies right hemisphere influences, contributes to the involvement of the transcallosal conduction channel in the formation of spatial-motor asymmetry.     

Caveolin-1 regulates nitric oxide-mediated matrix metalloproteinases activity and blood-brain barrier permeability in focal cerebral ischemia and reperfusion injury

The roles of caveolin-1 (cav-1) in regulating blood-brain barrier (BBB) permeability are unclear yet. We previously reported that cav-1 was down-regulated and the production of nitric oxide (NO) induced the loss of cav-1 in focal cerebral ischemia and reperfusion injury. The present study aims to address whether the loss of cav-1 impacts on BBB permeability and matrix metalloproteinases (MMPs) activity during cerebral ischemia-reperfusion injury. We found that focal cerebral ischemia-reperfusion down-regulated the expression of cav-1 in isolated cortex microvessels, hippocampus, and cortex of ischemic brain. The down-regulation of cav-1 was correlated with the increased MMP-2 and -9 activities, decreased tight junction (TJ) protein zonula occludens (ZO)-1 expression and enhanced BBB permeability. Treatment of N(G) -nitro-L-arginine methyl ester [L-NAME, a non-selective nitric oxide synthase (NOS) inhibitor] reserved the expression of cav-1, inhibited MMPs activity, and reduced BBB permeability. To elucidate the roles of cav-1 in regulating MMPs and BBB permeability, we used two approaches including cav-1 knockdown in cultured brain microvascular endothelial cells (BMECs) in vitro and cav-1 knockout (KO) mice in vivo. Cav-1 knockdown remarkably increased MMPs activity in BMECs. Meanwhile, with focal cerebral ischemia-reperfusion, cav-1 deficiency mice displayed higher MMPs activities and BBB permeability than wild-type mice. Interestingly, the effects of L-NAME on MMPs activity and BBB permeability was partly reversed in cav-1 deficiency mice. These results, when taken together, suggest that cav-1 plays important roles in regulating MMPs activity and BBB permeability in focal cerebral ischemia and reperfusion injury. The effects of L-NAME on MMPs activity and BBB permeability are partly mediated by preservation of cav-1.     

Effect of Vitamin E on Blood-Brain Barrier Permeability in Aged Rats with PTZ-Induced Convulsions

The effect of vitamin E on blood-brain barrier (BBB) permeability was studied under conditions of pentylenetetrazole (PTZ)-induced convulsions in aged (23- to 24-month-old) male albino rats; Evans Blue was used as a tracer. The BBB permeability was found to increase considerably in rats with PTZ-evoked seizures; the Evans Blue contents in the left and right hemispheres and cerebellum + brainstem region were significantly higher than those in the control. Vitamin E at a dose of 70 mg/kg exerted practically no beneficial effect on the increased BBB permeability in rats with seizures, while a greater dose of vitamin E (700 mg/kg) exerted a significant protective effect, especially with respect to the cerebellum + brainstem regions (P < 0.01). The seizure-related rise in the arterial blood pressure was also smaller in the latter experimental group. Thus, our observations confirm the importance of the vitamin E dose as a protective factor for BBB permeability and demonstrate that the dose dependence of this antioxidant in aged animals differs from that in younger organisms.     

Hemispheric asymmetry of the space-motion component of a food-conditioned motor reflex

The preference of movement direction in the process of motor food conditioned reaction has been investigated in rats with intact brain and after unilateral cortical inactivation. It was shown that the degree of motorspatial preference diminished with the maturation of reaction. At the high level of differentiation the valid preference was shown only in 38% of animals investigated but it was absent in the rest of animals. After inactivation of right hemisphere cortex left-side preference occurred in the presence as well as in the absence of the original preference. Inactivation of the left hemisphere cortex is less significant; it influences the original preference of movement direction permanently affecting those animals which normally had evident preference. It is concluded that the right hemisphere cortex plays dominant part in both sensor and motorspatial components of motor food conditioned reaction. It is supposed that the definite relationship exists between the degree of preference of movement direction and the functional asymmetry of cerebral hemispheres.     

Paw preferences in cats (Felis silvestris catus) living in a household environment

Unrestrained, naı̈ve cats (Felis silvestris catus) (n=48: 28 males and 20 females), living in a natural domestic environment, were studied for paw preferences using a food reaching test. A total of 46% were right-preferent, 44% were left-preferent and 10% were ambilateral. 60% of the cats in our sample used one paw 100% of the time. This preference was stable over time (10 weeks), and was not influenced by the presence of food residue on the cats' non-preferred paw. There was no difference between male and female cats in the proportions of left and right paw-preferent individuals. We have reviewed the literature reporting paw preferences in cats and conclude that in static food-reaching tests, domestic cats show a marked paw preference with an equal distribution of left- and right-preferent individuals. They do not, however, show a group or population bias toward the use of any one paw. There are no significant sex differences. In contrast, there is previously published evidence which appears to suggest that moving-target reaching tests uncover a left-sided behavioural asymmetry.