Etude du nerf phrenique chez le cobaye (Cavia porcellus, L., 1756)

The aim of the present study to ascertain the mode of origin of the phrenic nerve and to provide a morphological basis for experimental studies of this nerve in the guinea pig. In sketches made of the dissections, in 10 male and 10 female guinea pigs adults, the modes of origin of the phrenic roots were demonstrated to arise from the fourth to the seventh cervical nerves. Four types of origin could be distinguished. The phrenic nerve of the guinea pig has three or four roots.

Localization of calcitonin receptor-like receptor and receptor activity modifying protein 1 in enteric neurons, dorsal root ganglia, and the spinal cord of the rat

Calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) comprise a receptor for calcitonin gene related peptide (CGRP) and intermedin. Although CGRP is widely expressed in the nervous system, less is known about the localization of CLR and RAMP1. To localize these proteins, we raised antibodies to CLR and RAMP1. Antibodies specifically interacted with CLR and RAMP1 in HEK cells coexpressing rat CLR and RAMP1, determined by Western blotting and immunofluorescence. Fluorescent CGRP specifically bound to the surface of these cells and CGRP, CLR, and RAMP1 internalized into the same endosomes. CLR was prominently localized in nerve fibers of the myenteric and submucosal plexuses, muscularis externa and lamina propria of the gastrointestinal tract, and in the dorsal horn of the spinal cord of rats. CLR was detected at low levels in the soma of enteric, dorsal root ganglia (DRG), and spinal neurons. RAMP1 was also localized to enteric and DRG neurons and the dorsal horn. CLR and RAMP1 were detected in perivascular nerves and arterial smooth muscle. Nerve fibers containing CGRP and intermedin were closely associated with CLR fibers in the gastrointestinal tract and dorsal horn, and CGRP and CLR colocalized in DRG neurons. Thus, CLR and RAMP1 may mediate the effects of CGRP and intermedin in the nervous system. However, mRNA encoding RAMP2 and RAMP3 was also detected in the gastrointestinal tract, DRG, and dorsal horn, suggesting that CLR may associate with other RAMPs in these tissues to form a receptor for additional peptides such as adrenomedullin.

Long-Term Spinal Ventral Root Reimplantation, but not Bone Marrow Mononuclear Cell Treatment, Positively Influences Ultrastructural Synapse Recovery and Motor Axonal Regrowth

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Nerve root sedimentation sign: evaluation of a new radiological sign in lumbar spinal stenosis

Retrospective case-referent study.

Increased intraoperative epidural pressure in lumbar spinal stenosis patients with a positive nerve root sedimentation sign

Purpose The sedimentation sign (SedSign) has been shown to discriminate well between selected patients with and without lumbar spinal stenosis (LSS). The purpose of this study was to compare the pressure values associated with LSS versus non-LSS and discuss whether a positive SedSign may be related to increased epidural pressure at the level of the stenosis. Methods We measured the intraoperative epidural pressure in five patients without LSS and a negative SedSign, and in five patients with LSS and a positive SedSign using a Codman TM catheter in prone position under radioscopy. Results Patients with a negative SedSign had a median epidural pressure of 9 mmHg independent of the measurement location. Breath and pulse-synchronous waves accounted for 1–3 mmHg. In patients with monosegmental LSS and a positive SedSign, the epidural pressure above and below the stenosis was similar (median 8–9 mmHg). At the level of the stenosis the median epidural pressure was 22 mmHg. A breath and pulse-synchronous wave was present cranial to the stenosis, but absent below. These findings were independent of the cross-sectional area of the spinal canal at the level of the stenosis. Conclusions Patients with LSS have an increased epidural pressure at the level of the stenosis and altered pressure wave characteristics below. We argue that the absence of sedimentation of lumbar nerve roots to the dorsal part of the dural sac in supine position may be due to tethering of affected nerve roots at the level of the stenosis.

Clinical validity of the nerve root sedimentation sign in patients with suspected lumbar spinal stenosis

BACKGROUND CONTEXT The nerve root sedimentation sign in transverse magnetic resonance imaging has been shown to discriminate well between selected patients with and without lumbar spinal stenosis (LSS), but the performance of this new test, when used in a broader patient population, is not yet known. PURPOSE To evaluate the clinical performance of the nerve root sedimentation sign in detecting central LSS above L5 and to determine its potential significance for treatment decisions. STUDY DESIGN Retrospective cohort study. PATIENT SAMPLE One hundred eighteen consecutive patients with suspected LSS (52% women, median age 62 years) with a median follow-up of 24 months. OUTCOME MEASURES Oswestry disability index (ODI) and back and leg pain relief. METHODS We performed a clinical test validation study to assess the clinical performance of the sign by measuring its association with health outcomes. Subjects were patients referred to our orthopedic spine unit from 2004 to 2007 before the sign had been described. Based on clinical and radiological diagnostics, patients had been treated with decompression surgery or nonsurgical treatment. Changes in the ODI and pain from baseline to 24-month follow-up were compared between sedimentation sign positives and negatives in both treatment groups. RESULTS Sixty-nine patients underwent surgery. Average baseline ODI in the surgical group was 54.7%, and the sign was positive in 39 patients (mean ODI improvement 29.0 points) and negative in 30 (ODI improvement 28.4), with no statistically significant difference in ODI and pain improvement between groups. In the 49 patients of the nonsurgical group, mean baseline ODI was 42.4%; the sign was positive in 18 (ODI improvement 0.6) and negative in 31 (ODI improvement 17.7). A positive sign was associated with a smaller ODI and back pain improvement than negative signs (both p<.01 on t test). CONCLUSIONS In patients commonly treated with decompression surgery, the sedimentation sign does not appear to predict surgical outcome. In nonsurgically treated patients, a positive sign is associated with more limited improvement. In these cases, surgery might be effective, but this needs investigation in prospective randomized trials (Australian New Zealand Clinical Trial Registry, number ACTRN12610000567022).

A microchannel neuroprosthesis for bladder control after spinal cord injury in rat

A severe complication of spinal cord injury is loss of bladder function (neurogenic bladder), which is characterized by loss of bladder sensation and voluntary control of micturition (urination), and spontaneous hyperreflexive voiding against a closed sphincter (detrusor-sphincter dyssynergia). A sacral anterior root stimulator at low frequency can drive volitional bladder voiding, but surgical rhizotomy of the lumbosacral dorsal roots is needed to prevent spontaneous voiding and dyssynergia. However, rhizotomy is irreversible and eliminates sexual function, and the stimulator gives no information on bladder fullness. We designed a closed-loop neuroprosthetic interface that measures bladder fullness and prevents spontaneous voiding episodes without the need for dorsal rhizotomy in a rat model. To obtain bladder sensory information, we implanted teased dorsal roots (rootlets) within the rat vertebral column into microchannel electrodes, which provided signal amplification and noise suppression. As long as they were attached to the spinal cord, these rootlets survived for up to 3 months and contained axons and blood vessels. Electrophysiological recordings showed that half of the rootlets propagated action potentials, with firing frequency correlated to bladder fullness. When the bladder became full enough to initiate spontaneous voiding, high-frequency/amplitude sensory activity was detected. Voiding was abolished using a high-frequency depolarizing block to the ventral roots. A ventral root stimulator initiated bladder emptying at low frequency and prevented unwanted contraction at high frequency. These data suggest that sensory information from the dorsal root together with a ventral root stimulator could form the basis for a closed-loop bladder neuroprosthetic. Copyright © 2013, American Association for the Advancement of Science

Differential expression of ATP7A, ATP7B and CTR1 in adult rat dorsal root ganglion tissue

Background: ATP7A, ATP7B and CTR1 are metal transporting proteins that control the cellular disposition of copper and platinum drugs, but their expression in dorsal root ganglion (DRG) tissue and their role in platinum-induced neurotoxicity are unknown. To investigate the DRG expression of ATP7A, ATP7B and CTR1, lumbar DRG and reference tissues were collected for real time quantitative PCR, RT-PCR, immunohistochemistry and Western blot analysis from healthy control adult rats or from animals treated with intraperitoneal oxaliplatin (1.85 mg/kg) or drug vehicle twice weekly for 8 weeks.
Results: In DRG tissue from healthy control animals, ATP7A mRNA was clearly detectable at levels similar to those found in the brain and spinal cord, and intense ATP7A immunoreactivity was localised to the cytoplasm of cell bodies of smaller DRG neurons without staining of satellite cells, nerve fibres or co-localisation with phosphorylated heavy neurofilament subunit (pNF-H). High levels of CTR1 mRNA were detected in all tissues from healthy control animals, and strong CTR1 immunoreactivity was associated with plasma membranes and vesicular cytoplasmic structures of the cell bodies of larger-sized DRG neurons without co-localization with ATP7A. DRG neurons with strong expression of ATP7A or CTR1 had distinct cell body size profiles with minimal overlap between them. Oxaliplatin treatment did not alter the size profile of strongly ATP7A-immunoreactive neurons but significantly reduced the size profile of strongly CTR1-immunoreactive neurons. ATP7B mRNA was barely detectable, and no specific immunoreactivity for ATP7B was found, in DRG tissue from healthy control animals.
Conclusions: In conclusion, adult rat DRG tissue exhibits a specific pattern of expression of copper transporters with distinct subsets of peripheral sensory neurons intensely expressing either ATP7A or CTR1, but not both or ATP7B. The neuron subtype-specific and largely non-overlapping distribution of ATP7A and CTR1 within rat DRG tissue may be required to support the potentially differing cuproenzyme requirements of distinct subsets of sensory neurons, and could influence the transport and neurotoxicity of oxaliplatin.