Effect of oxidative stress in rostral ventrolateral medulla on sympathetic hyperactivity after traumatic brain injury

Sympathetic hyperactivity occurs in a subgroup of patients after traumatic brain injury (TBI). The rostral ventrolateral medulla (RVLM) is a key region for the activity of sympathetic nervous system. Oxidative stress in the RVLM is proved to be responsible for the increased level of sympathetic activity in animal models of hypertension and heart failure. In this study, we investigated whether oxidative stress in the RVLM contributed to the development of sympathetic hyperactivity after TBI in rats. Model of diffuse axonal injury was induced using Sprague‐Dawley rats, and level of mean arterial pressure (MAP) and plasma Norepinephrine (NE) was measured to evaluate the sympathetic activity. For the assessment of oxidative stress, expression of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) in the RVLM was determined. Microinjection of Tempol into the RVLM was performed to determine the effect of oxidative stress on sympathetic hyperactivity. According to the results, TBI led to elevated MAP and plasma NE in rats. It also induced a significantly increased level of ROS, MDA production and decreased level of SOD in the RVLM. The sympathetic activity, ROS, and MDA in the RVLM decreased significantly after microinjection of Tempol. Therefore, the present results suggested that oxidative stress in the RVLM was involved in the development of sympathetic hyperactivity following TBI.     

Administrations of thalidomide into the rostral ventromedial medulla produce antinociceptive effects in a rat model of postoperative pain

The rostral ventromedial medulla (RVM) is highly involved in pain signal transmissions. Previous studies have shown that thalidomide is anti‐nociceptive. Thus, we evaluated the neurobiological mechanisms of thalidomide in the RVM in the regulation of postoperative pain. We used a rat model of postoperative pain to investigate the effects of intra‐RVM thalidomide treatments on postoperative pain, and evaluate the role of cannabinoid receptors in the effects of intra‐RVM thalidomide treatments on GABAergic neurotransmission in the RVM neurons. We found intra‐RVM thalidomide treatments reduced incisional surgery induced mechanical allodynia. This phenomenon was associated with attenuation of the frequency and amplitude of miniature inhibitory postsynaptic currents (mIPSCs) and spontaneous IPSCs (sIPSCs) in RVM neurons. Furthermore, applications of WIN 55,212‐3 mesylate, a non‐selective cannabinoid receptor antagonist reversed the effects of repeated thalidomide treatment on the frequency but not the amplitude of mIPSCs and sIPSCs. Finally, we found that repeated thalidomide treatment robustly enhanced CB2 receptor expression, but slightly reduced CB1 receptor expression, in the RVM. These results suggested that the antinociceptive effects of thalidomide in the RVM likely involve the attenuation of GABA release, which are critically regulated by cannabinoid receptors.     

Distinct patterns of neuronal inputs and outputs of the juxtaparaventricular and suprafornical regions of the lateral hypothalamic area in the male rat

We have analyzed at high resolution the neuroanatomical connections of the juxtaparaventricular region of the lateral hypothalamic area (LHAjp); as a control and in comparison to this, we also performed a preliminary analysis of a nearby LHA region that is dorsal to the fornix, namely the LHA suprafornical region (LHAs). The connections of these LHA regions were revealed with a coinjection tract-tracing technique involving a retrograde (cholera toxin B subunit) and anterograde (Phaseolus vulgaris leucoagglutinin) tracer. The LHAjp and LHAs together connect with almost every major division of the cerebrum and cerebrospinal trunk, but their connection profiles are markedly different and distinct. In simple terms, the connections of the LHAjp indicate a possible primary role in the modulation of defensive behavior; for the LHAs, a role in the modulation of ingestive behavior is suggested. However, the relation of the LHAjp and LHAs to potential modulation of these behaviors, as indicated by their neuroanatomical connections, appears to be highly integrative as it includes each of the major functional divisions of the nervous system that together determine behavior, i.e., cognitive, state, sensory, and motor. Furthermore, although a primary role is indicated for each region with respect to a particular mode of behavior, intermode modulation of behavior is also indicated. In summary, the extrinsic connections of the LHAjp and LHAs (so far as we have described them) suggest that these regions have a profoundly integrative role in which they may participate in the orchestrated modulation of elaborate behavioral repertoires.     

Olfactory ensheathing cells: Attractant of neural progenitor migration to olfactory bulb

Olfactory ensheathing cells (OECs) are the glial cells that derive from the olfactory placode, envelop olfactory axons in the course of migration from the olfactory epithelium to the olfactory bulb and reside primarily in the olfactory nerve layer. OECs transplantation as a promising experimental therapy for axonal injuries has been intensively studied; however, little is known about their roles in olfactory bulb development. In this study, we examined the effects of OECs on the migration of neural progenitors in rostral migratory stream (RMS). Initially, the neurosphere migration assay showed that OEC‐conditioned medium promoted progenitors to migrate from RMS neurospheres in a concentration dependent manner. Moreover, co‐culturing OECs nearby the RMS explants led to asymmetric migration of explants in different developing stages. However, OECs could influence the migration in a distance not further than 1.5 mm. Finally, slice assay that mimic the circumstance in vivo revealed that OECs had a chemoattractive activity on RMS neural progenitors. Together, these results demonstrate that OECs attract neural progenitors in RMS through the release of diffusible factors and it is likely that OECs mainly influence radial migration in the olfactory bulb but not tangential migration of the RMS invivo during development. This suggests a previously unknown function for OECs in olfactory development and a novel mechanism underlying the targeting of RMS cells. © 2010 Wiley‐Liss, Inc.     

Functional connectivity of cortical motor areas in the resting state in Parkinson's disease

Parkinson's disease (PD) patients have difficulty in initiating movements. Previous studies have suggested that the abnormal brain activity may happen not only during performance of self‐initiated movements but also in the before movement (baseline or resting) state. In the current study, we investigated the functional connectivity of brain networks in the resting state in PD. We chose the rostral supplementary motor area (pre‐SMA) and bilateral primary motor cortex (M1) as “seed” regions, because the pre‐SMA is important in motor preparation, whereas the M1 is critical in motor execution. FMRIs were acquired in 18 patients and 18 matched controls. We found that in the resting state, the pattern of connectivity with both the pre‐SMA or the M1 was changed in PD. Connectivity with the pre‐SMA in patients with PD compared to normal subjects was increased connectivity to the right M1 and decreased to the left putamen, right insula, right premotor cortex, and left inferior parietal lobule. We only found stronger connectivity in the M1 with its own local region in patients with PD compared to controls. Our findings demonstrate that the interactions of brain networks are abnormal in PD in the resting state. There are more connectivity changes of networks related to motor preparation and initiation than to networks of motor execution in PD. We postulate that these disrupted connections indicate a lack of readiness for movement and may be partly responsible for difficulty in initiating movements in PD. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Motion integration deficits are independent of magnocellular impairment in Parkinson's disease

Motion processing involves multiple hierarchical steps, from the magnocellular pathway, sensitive to high temporal frequency modulations, to subsequent motion integration within the visual cortical dorsal stream. We have tested whether motion integration deficits in mild Parkinson disease (PD) can be explained by visual deficits in earlier processing nodes. Contrast sensitivity deficits in the magnocellular pathway, were compared with speed discrimination of local dots moving in random directions, speed and direction discrimination of moving surfaces and motion integration as measured by 2D coherence thresholds (n = 27). We have found that low-level magnocellular impairment in PD does not explain deficits in subsequent steps in motion processing. High-level performance was abnormal in particular for tasks requiring perception of coherently moving surfaces. Motion coherence deficits were predictive of visuomotor impairment, corroborating a previous magnetic stimulation study in normal subjects. We conclude that dorsal stream deficits in PD have a high-level visual cortical basis independent of low-level magnocellular damage.     

Is there a left hemispheric asymmetry for tool affordance processing?

The perception of tools vs. other objects has been shown to activate the left premotor and somatosensory cortex, which represents object affordance associated with tool manipulability (Proverbio, Adorni, & D'Aniello, 2011). The question of whether hemispheric asymmetry depends on right hand use or is linked to a hemispheric functional specialization for fine-grained precision movement is unclear. Thus, in this paper, ERPs were recorded from 128 sites in response to the visual presentation of bidimensional (2D) pictures depicting unimanual (e.g., a hammer) and bimanual (e.g., a handlebar) tools (Study 1). Central N2 and prefrontal N400 components were much larger for bimanual than unimanual tools (over the left hemisphere for N400). SwLORETAs performed for both components showed at first the activation of the left parietal cortex (BA39) and then of the right homologous (BA40) one, for both grips but stronger for the bimanual coordination. At all times and for both grips, the left premotor cortex (BA6) was involved in coding action affordance, while only unimanual tools activated the left postcentral gyrus (BA3).     

A general deficit of the 'automatic pilot' with posterior parietal cortex lesions?

Lesions of the parieto-occipital junction (POJ) in humans cause gross deviations of reaching movements and impaired grip formation if the targets are located in the subjects' peripheral visual field. Movements to central targets are typically less impaired. This disorder has been termed "optic ataxia". It has been suggested that a general deficit of online corrections under central as well as peripheral viewing conditions might be sufficient to explain this discrepancy. According to this hypothesis, patients with optic ataxia should demonstrate an impaired online correction of grip aperture under central viewing conditions if the target object changes its size during the grasping movement. We investigated this prediction in a patient with optic ataxia (I.G.) in a virtual visuo-haptic grasping task. We imposed an isolated need for online corrections of the hand aperture independently of positional changes of the target object. While we found some general inaccuracies of her grasping movements, the patient did not show a specific impairment of online adjustment of grip aperture. On the contrary, I.G. smoothly adjusted her grip aperture comparable to healthy subjects. A general deficit of fast movement correction affecting targets in peripheral as well as central visual fields thus does not appear to account for the overt visuomotor deficits in optic ataxia. Rather, it seems more likely that an anatomical dissociation between visuomotor pathways related to actions in the central and in the peripheral visual field underlies the dissociation of visuomotor performance depending on the retinotopic target position in optic ataxia.     

Genetic characterization of an H13N2 low pathogenic avian influenza virus isolated from gulls in China

Low pathogenic avian influenza viruses circulate in wild birds but are occasionally transmitted to other species, including poultry, mammals and humans. To date, infections with low pathogenic avian influenza viruses of HA subtype 6, HA subtype 7, HA subtype 9 and HA subtype 10 among humans have been reported. However, the epidemiology, genetics and ecology of low pathogenic avian influenza viruses have not been fully understood thus far. Therefore, persistent surveillance of low pathogenic avian influenza virus infections in wild birds and other species is needed. Here, we found a low pathogenic avian influenza virus of the subtype H13N2 (abbreviated as WH42) in black‐tailed gulls in China. All gene sequences of this H13N2 virus were determined and used for subsequent analysis. Phylogenetic analysis of the HA gene and NA gene indicated that WH42 was derived from the Eurasian lineage. We analysed the timing of the reassortment events and found that WH42 was a reassortant whose genes were transferred from avian influenza viruses circulating in Asia, Europe and North America. Additionally, WH42 possessed several molecular markers associated with mammalian virulence and mammalian transmissibility. Interestingly, we also found low but detectable haemagglutination inhibition antibodies against H13N2 low pathogenic avian influenza virus in serum samples collected from chickens. Taken together, our findings show that the H13 virus may have been introduced into poultry and that sustainable surveillance in gulls and poultry is required.     

Glutamate circuits in selected medullo-spinal areas regulating cardiovascular function

1. The importance of the medullo-spinal neuronal pools in the regulation of cardiovascular function has been known for a long time. However, important groups of these neurons, interconnections between them and the neurotransmitters released at their projections have been identified with certainty only during the past two decades. 2. Some of the medullo-spinal neuronal pools mediating cardiovascular function include the nucleus tractus solitarius, caudal ventrolateral medullary depressor area, rostral ventrolateral medullary pressor area, nucleus ambiguus and intermediolateral cell column of the thoracolumbar spinal cord. Interactions between these selected neuronal groups and neurotransmitters in the pathways connecting them are discussed in the present short review.