Serotonergic interhemispheric asymmetry: Neurochemical and pharmaco-EEG evidence

1. Postmortem neurochemical investigations revealed interhemispheric asymmetry in the mediofrontal region of human brain. Significantly higher right hemisphere serotonin metabolite (5HIAA) content as well as increased maximal imipramine binding (IB) were found in the right hemisphere than in the left side.

2. IB did not show a gender difference in the mediofrontal area. However, women had higher IB in the right orbital frontal cortex than did men.

3. In vivo pharmaco-EEG results tend to support the postmortem neurochemical data. Intravenous chlorimipramine resulted in an asymmetric topographic distribution of the P300 auditory evoked potential, peak amplitudes were shifted to the right hemisphere.     

Framework for interactive million-neuron simulation.

SUMMARY: Large simulations have become increasingly complex in many fields, tending to incorporate scale-dependent modeling and algorithms and wide-ranging physical influences. This scale of simulation sophistication has not yet been matched in neuroscience. The authors describe a framework aimed at enabling natural interaction with complex simulations: their configuration, initial conditions, monitoring, and analysis. The architecture is built on three cornerstone components: active probes, adaptive data capture, and visual interface. The resulting synthesis will enable interactive exploration of live simulations running on supercomputing platforms.     

Smoking delays chondrogenesis in a mouse model of closed tibial fracture healing.

Smoking delays the healing process and increases morbidity associated with many common musculoskeletal disorders, including long bone fracture. In the current study, a murine model of tibial fracture healing was used to test the hypothesis that smoking delays chondrogenesis after fracture. Mice were divided into two groups, a nonsmoking control group and a group exposed to cigarette smoke for 1 month prior to surgical tibial fracture. Mice were euthanized at 7, 14, and 28 days after surgery. The outcomes measured were immunohistochemical staining for type II collagen protein expression as a marker of cartilage matrix and proliferating cell nuclear antigen (PCNA) staining to measure proliferation at the site of injury. Toluidine blue staining and histomorphometry were used to quantify areas of cartilaginous and noncartilaginous fracture callus. Radiographs were analyzed for evidence of remodeling after injury. At day 7 after injury, mice exposed to cigarette smoke had a smaller fracture callus with less cartilage matrix compared to controls. Proliferation was present at high levels in both groups at this time point, but proliferating cells had a more immature morphology in the smoking group. At day 14, chondrogenesis was more active in smokers compared to controls, while a higher percentage of bone was present in the control animals. At day 28, X-ray analysis revealed a larger fracture callus remaining in the smoking animals. Together, these findings show that the chondrogenic phase of tibial fracture healing is delayed by smoking. This study represents, to our knowledge, the first analysis of molecular and cellular mechanisms of healing in a smoking mouse fracture model.     

Reversible reorganisation of the motor cortical representation of the hand in cervical dystonia.

Previous work has suggested that there may be a widespread disturbance of motor control mechanisms in patients with cervical dystonia. In the present study, we used transcranial magnetic stimulation to investigate the topography of the corticomotor projection to the abductor pollicis brevis (APB) muscle in 10 subjects with idiopathic torticollis. Threshold-adjusted stimuli were delivered at multiple scalp sites during a low-level voluntary contraction of the APB, and maps were generated of motor evoked potential amplitude versus scalp site. The cortical maps for the APB on the side opposite to the direction of head rotation were displaced laterally or posteriorly in all subjects and reverted to a more normal position after botulinum toxin injection of the cervical muscles in 5 subjects. The findings point to a reversible reorganisation of the corticomotor representation of the hand on the same side as the sternocleidomastoid (SCM) muscle that is involved in producing the dystonia. These results provide further evidence for the involvement of cortical centres and for a more widespread abnormality of motor control mechanisms in focal dystonia. The findings also support the notion that head turning is chiefly mediated by the hemisphere ipsilateral to the direction of the head rotation by means of a corticomotor projection to the contralateral SCM.     

Vascular injury during anterior lumbar surgery.

BACKGROUND CONTEXT: With the number of anterior lumbar procedures expected to increase significantly over the next few years, it is important for spine surgeons to have a good understanding about the incidence of vascular complications during these operations. PURPOSE: To determine the incidence of vascular injury in 1,315 consecutive cases undergoing anterior lumbar surgery at various levels from L2 to S1. STUDY DESIGN/SETTING: Patients undergoing anterior lumbar surgery were studied. PATIENT SAMPLE: A total of 1,310 consecutive patients undergoing 1,315 anterior lumbar procedures between August 1997 and December 2002 were included in the study. OUTCOME MEASURES: All patients were evaluated for incidence of vascular injury during and immediately after surgery. METHOD: A concurrent database was maintained on all these cases. All the patients had distal pulse evaluation preoperatively. Patients with venous injuries were further analyzed to determine location and extent of injury, amount of blood loss, completion of the procedure and postoperative sequelae. Patients with pulse deficits or evidence of ischemia during or immediately after surgery were further analyzed in particular in relation to demographic, preoperative variables and management. RESULTS: Six patients were identified as having left iliac artery thrombosis (0.45%), and 19 had major vein lacerations (1.4%). CONCLUSION: This study shows that the incidence of vascular injury is relatively low (25 in 1,315 or 1.9%). Because only five of these patients experienced significant sequelae from the approach, it appears that anterior lumbar surgery is quite safe, although it must be carried out with utmost respect for the vessels to avoid possible catastrophic outcomes.     

Intrinsic nerves in the mammalian colon: confirmation of a plexus at the circular muscle-submucosal interface

Slow waves in the small intestine seem to arise in plexuses of neurites with interstitial cells of Cajal. In the colon, slow waves appear to arise at the circular muscle - submucosal interface. We therefore sought a plexus at this surface in the colon in the cat, dog, ferret, opossum, rabbit, rat, guinea-pig and man. Segments from all levels of the colon were stained by the Champy-Maillet osmic acid-zinc iodide method and cut into serial 25 micron sections in the plane of the muscle layers. A dense network of neurites with abundant interstitial cells of Cajal was found at the circular muscle - submucosal interface in all species except rabbit. Neurites in this plexus appeared to arise from the deep plexus of the submucosa (Schabadasch's or Henle's plexus). It was not found in the small intestine and stomach. A similar plexus was found in the interstices of the myenteric plexus in the colon. Interstitial cells of Cajal in both plexuses were positive for the NADH-diaphorase stain, but not for silver impregnation. The possible roles of the plexuses of neurites and interstitial cells of Cajal at the circular muscle - submucosal interface and at the plane of the myenteric plexus in the generation of rhythmic activity in the colon are discussed.     

Corticosteroids for the Enhancement of Fetal Lung Maturity: Impact on the Gravida with Preeclampsia and the HELLP Syndrome

Summary: This study was undertaken to determine maternal impact of corticosteroids administered for the promotion of fetal lung maturity in mothers with the HELLP syndrome. Twenty-seven of 427 women with the HELLP syndrome treated between 1980–1991 received a full course of steroids prior to preterm delivery. This group was compared to 27 matched control patients with the HELLP syndrome who received no corticosteroids. Subjects were matched for maternal age, race, sex of the fetus, and severity of the HELLP syndrome. The antepartum platelet count stabilized or increased in 25 of 27 steroid-treated women in contrast to 0 of 15 control women (p <0.00001). In comparison to control patients, LDH serum concentrations in steroid-treated patients stabilized or decreased and the SGOT/AST and SGPT/ALT stabilized or decreased during therapy (p < 0.005). The interval from delivery to platelet nadir in patients with Class III HELLP syndrome was shorter in the steroid-treated group (p<0.008) than in untreated patients.     

TNFα Inhibits Schwann Cell Proliferation, Connexin46 Expression, and Gap Junctional Communication

Schwann cell responses to nerve injury are stimulated, in part, by inflammatory cytokines. This study compares changes in the phenotype of cultured Schwann cells after exposure to the cytokine tumor necrosis factor (TNF)-α or the mitogen neu differentiation factor (NDF)-β. TNFα inhibited proliferation in a dose-dependent manner without altering Schwann cell survival. TNFα also reduced both gap junctional conductance and Lucifer yellow dye coupling between Schwann cells. Moreover, both P₀and glial fibrillary acidic protein (GFAP) immunoreactivity were reduced. By contrast, NDFβ initially had little effect on cell division although it reduced junctional coupling within 8 h. However, by 48 h, NDFβ stimulated proliferation with a concomitant increase in coupling. Dividing Schwann cells (BrdU⁺) were preferentially dye coupled compared to nondividing cells, indicating an association between proliferation and coupling. Moreover, cultured Schwann cells expressed connexin46 mRNA and protein, and changes in the levels of the protein correlated with the degree of proliferation and coupling. The data thus provide evidence for cytokine-induced modulation of Schwann cell antigenic phenotype, proliferation, and gap junction properties. These observations suggest that enhanced gap junctional communication among Schwann cells after nerve injury could help to coordinate cellular responses to the injury, and that TNFα may be a signal which terminates proliferation as well as junctional communication.     

Effect of amiloride on electrolyte concentrations and rubidium uptake in principal and mitochondria-rich cells of frog skin

The role of mitochondria-rich cells (MR cells) in transepithelial Na transport was investigated by determining electrolyte concentrations and Rb uptake in individual cells of frog skin epithelium using electron microprobe analysis. Measurements were performed under control conditions and after blocking the transepithelial Na transport with amiloride. Under control conditions, Na and Cl concentrations of MR cells scattered much more than those of principal cells and ranged from a few up to more than 30 mmol/kg wet weight. Rb uptake from the basal side into individual MR cells also showed a large variation and was, on the average, much less pronounced than into the principal cells. In principal cells, amiloride reduced the Na concentration and Rb accumulation. In contrast, no effect was observed upon electrolyte concentration and Rb uptake of MR cells. Rb uptake was correlated to the Na concentration of MR cells both under control conditions and after amiloride. It is concluded that, in contrast to the principal cells, MR cells are not involved in amiloride-sensitive transepithelial Na transport and that their Na/K-pump activity is very low.