Assessment of orbital hemodynamic changes in primary open angle glaucoma by color Doppler imaging.

PURPOSE: To assess changes in orbital vessels by Color Doppler Imaging (CDI) in patients with Primary Open Angle Glaucoma (POAG). METHODS: This cross-sectional study included 120 subjects - 60 patients with POAG and 60 controls, all of whom underwent full ophthalmological examinations and orbital CDI. The Ophthalmic Artery (OA), Central Retinal Artery (CRA) and Ciliary Arteries (CA) were identified, and for each of them, we measured Peak Systolic Velocity (PSV), End Diastolic velocity (EDV) and Resistivity Index (RI). RESULTS: The PSV of the OA and CRA were significantly lower in patients with POAG compared to normal controls (P<0.0001, < 0.009 respectively). The EDV in the OA, CRA and CA were significantly lower than in normal controls (P<0.0001). The RI of the OA, CRA and CA were significantly higher in patients with POAG compared to controls (P<0.0001). The EDV of the OA showed significant negative correlation with duration of glaucoma (r=-0.37, P<0.042). The EDV of the CA showed significant negative correlation with intraocular pressure (IOP) (r=-0.86 and P value 0.0001). The PSV and EDV of the CRA showed significant negative correlation with IOP (r=-0.45, r=-0.73, P values 0.011, and 0.0001 respectively), and the RI of the CRA showed significant positive correlation with IOP (r=0.42 and P value 0.021). CONCLUSION: CDI is a feasible, noninvasive, safe tool for the assessment of hemodynamic changes in the orbital arteries of POAG patients. The orbital arteries showed significantly lower flow velocities and increased resistivity indices in patients with POAG compared to the control group, and these changes were correlated with glaucoma duration and IOP.

The use of single phrenic axon recordings to assess diaphragm recovery after cervical spinal cord injury.

Electrophysiological recordings taken from the whole phrenic nerve have been utilized previously to describe the gradual increase in functional recovery of a hemidiaphragm paralyzed by ipsilateral C2 hemisection during the crossed phrenic phenomenon (CPP). Although the increase in activity has been temporally correlated with hemisection-induced morphological alterations of the phrenic nucleus, suggesting an association of the increased activity with the morphological alterations, whole phrenic nerve recordings during the CPP can provide only limited information. The purpose of the present study, therefore, was to use phrenic single-axon recording techniques to better understand the mechanisms underlying the recovery of respiratory activity during the expression of the CPP. Recordings from the whole phrenic nerve on the right side and from small fascicles of the phrenic nerve that show only the activity of single phrenic axons (units) on the left side were made in the neck before left spinal hemisection and during the CPP. The results indicated that there were two types of units firing before and during the CPP: an early- and a late-firing unit based on the time of their firing onset in relation to whole phrenic nerve activity. Ten early units and 25 late units were identified according to the shape of their spikes before hemisection as well as during the CPP. In addition to these units, 20 new units were recruited during CPP activity. These new units were mainly of the late-onset type. The results also indicated that there was a significant increase in the frequency of firing of both early and late units. The results specifically indicate therefore that the increase in respiratory activity recorded previously in the whole phrenic nerve during the CPP is most likely due to: (i) an increase in firing frequency for both early- and late-firing units and (ii) a recruitment of predominantly late-firing units into the CPP response. These results are important in understanding more completely the mechanisms that can facilitate recovery of the diaphragm after spinal cord injury.

Quantitative assessment of respiratory function following contusion injury of the cervical spinal cord.

In this study, we describe a new method for quantitative assessment of phrenic inspiratory motor activity in two models of cervical spinal cord contusion injury. Anesthetized rats received contusion injury either to the descending bulbospinal respiratory pathway on one side of the spinal cord alone (C2 lateralized contusion) or to both the descending pathway, as well as the phrenic motoneuron pool bilaterally (C4/C5 midline contusion). Following injury, respiratory-associated phrenic nerve motor activity was recorded under standardized and then asphyxic conditions. Phrenic nerve efferent activity was rectified, integrated, and quantitated by determining the mean area under the integrated neurograms. The mean integrated area of the four inspiratory bursts recorded just before turning off the ventilator (to induce asphyxia) was determined and divided by the integrated area under the single largest respiratory burst recorded during asphyxia. This latter value was taken as the maximal inspiratory motor response that the rat was capable of generating during respiratory stress. Thus, a percentage of the maximal inspiratory motor drive was established for breathing in control and injured rats under standardized conditions. The results indicate that noninjured rats use 52 +/- 1.8% of maximal inspiratory motor drive under standardized conditions. In C2-contused rats, the results showed that while the percentage of maximal inspiratory motor drive on the noncontused side was similar to the control (55 +/- 4.1%), it was increased on the contused side (78 +/- 2.6%). In C4/5 lesions, the results indicate that this percentage was increased on both sides (77 +/- 4.4%). The results show the feasibility for performing quantitative evaluation of respiratory dysfunction in an animal model of cervical contusion injury. These findings lend to further development of this model for investigations of neuroplasticity and/or therapeutic interventions directed at ameliorating respiratory compromise following cervical spinal cord trauma.

Actions of systemic theophylline on hemidiaphragmatic recovery in rats following cervical spinal cord hemisection.

This study assesses the effects of theophylline on enhancing phrenic nerve discharge and functional hemidiaphragmatic recovery after C2 spinal cord hemisection in adult female rats. There were three separate groups of spinal hemisected rats and one nonhemisected group studied. Twenty-four hours following C2 spinal hemisection, ipsilateral phrenic nerve activity was recorded under standardized, normoxic and then hypoxic conditions. After 30 min, theophylline was administered and the recordings were repeated in group 1 animals. In group 2, activity in both phrenic nerves was recorded simultaneously before and after drug administration. In a third group of rats, both ipsilateral phrenic nerve and hemidiaphragmatic activities were monitored before and after the drug. In control nonhemisected animals under standardized recording conditions, the effects of theophylline were quantitatively assessed by determining the mean area under integrated phrenic nerve discharge waveforms before and after drug administration. Generally, theophylline induced biphasic effects; i.e., at a low dose (15 mg/kg) it evoked excitation, while at a high dose (30 mg/kg) depression of respiratory activity predominated. In group 2 animals, respiratory activity was induced in the nerve ipsilateral to the hemisection and enhanced in the contralateral phrenic nerve for up to 3 h after a single standard dose of theophylline (15 mg/kg). Prior to drug administration, there was an absence of respiratory-related activity in both the phrenic nerve and hemidiaphragm ipsilateral to C2 spinal cord hemisection. A standard dose of theophylline, however, induced recovery of activity in both the phrenic nerve and the left hemidiaphragm ipsilateral to the hemisection in group 3 animals. In control (nonhemisected) animals, theophylline enhanced phrenic nerve activity, but decreased the duration of respiratory bursts. These results show for the first time that theophylline can activate latent respiratory motor pathways and thus restore the respiratory drive to phrenic motoneurons lost by spinal cord injury. Respiratory activity is not only reestablished in the phrenic nerve made quiescent by hemisection, but it is also enhanced in the contralateral phrenic nerve. The drug also restores function to the hemidiaphragm paralyzed by the spinal cord hemisection. The findings may have clinical relevance to human cases of cervical spinal cord injury in which respiratory function is compromised.

Deafferentation-induced changes in neuropeptides of the adult rat dorsal horn following pronase injection of the sciatic nerve.

The effect of deafferentation on the neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), somatostatin (SS), and cholecystokinin (CCK) in the lumbar dorsal horn of the adult rat was examined by the indirect immunohistochemical method. Deafferentation was induced by injecting the sciatic nerve of anesthetized rats with proteolytic enzymes (20 mg pronase), which cause selective death of the nerve's ganglion cells and degeneration of their terminal arborization in the spinal cord. The density of immunolabel of each peptide was determined by using a computerized densitometry analysis system in two animal groups, i.e., short-term (10-13 days after injection) and long-term (4-9 months). In both groups, the deafferentation produced a significant ipsilateral depletion of CGRP, SP, CCK, and SS immunoreactivity. This depletion was limited to the area occupied by the sciatic terminals in the dorsal horn. In the long-term group, the loss of CGRP and SP staining was significantly less than that in the short-term animals, thus indicating partial recovery. A similar, but not statistically significant, trend was observed for CCK and SS. The large decrease in CGRP and SP seen in short-term animals reflects the large contribution of the sciatic nerve to the lumbar dorsal horn. The partial recovery of peptides demonstrates the plasticity of the nervous system and may parallel sprouting of primary afferents from other nerves, such as the saphenous nerve, as we have demonstrated in previous studies.

Mechanosensitive afferent units in the lumbar facet joint.

The purpose of this study was to characterize somatosensory units of the lumbar facet joint, which may play a central role in idiopathic low-back pain. A laminectomy was performed on the lumbar spine of adult male New Zealand White rabbits. Receptive fields of mechanosensitive afferent units were investigated in the lumbar facet joint and adjacent surrounding tissues, and electrophysiological recordings were obtained from filaments of the dorsal root. Twenty-four units were identified in the region of the facet joint: ten, in the capsule of the joint; twelve, in the border regions between capsule and muscle or tendon; and two, in the ligamentum flavum. Of these units, two had a conduction velocity that was slower than 2.5 meters per second (group IV), fifteen had a velocity ranging from 2.5 to twenty meters per second (group III), and seven had a velocity faster than twenty meters per second. Seven units had a von Frey threshold of more than 6.0 grams, thirteen had a threshold of less than 6.0 grams, and four were not examined. Seven units in the facet joint responded to movement of the joint. Fourteen other mechanosensitive units were found in the muscle, tendon, and interspinous ligament; seven had a conduction velocity of 2.5 to twenty meters per second, and seven had a velocity that was faster than twenty meters per second.

Sensory innervation of soft tissues of the lumbar spine in the rat.

The purpose of this study was to investigate neurophysiologically and anatomically the soft tissues of the dorsal compartment of the lumbar spine in order to understand better their possible role in low back pain. The focus was primarily on the lumbar facet joint and supraspinous ligament of the Sprague-Dawley rat. Microdissection of the dorsal ramus and electrophysiological and neuroanatomical studies of the dorsal ramus and its terminations in paravertebral tissue revealed that (a) there are mechanosensitive, slowly adapting fibers in the rat lumbar facet joint capsule; (b) there are slowly adapting, mechanosensitive units in the rat supraspinous ligaments that respond to tensile loading; both types of mechanosensitive units have high threshold; (c) mechanical stimulation of these tissues sometimes elicits afterdischarges lasting several minutes; (d) many extracellular recordings from the medial branch of the dorsal ramus appear to be reflex activity to mechanical stimulation; (e) silver impregnation of the rat joint capsule reveals individual axons, very few of which were encapsulated, suggesting that they terminate in free nerve endings; and (f) the nerves of the rat facet joint capsule contain 68, 160, and 200 kdalton polypeptide subunits of neurofilament protein (NFP). These results indicate that neurons of lumbar facet joint capsules and ligaments in the back are sensitive to mechanical strain and that the higher threshold neurons may serve a nociceptive (pain) function.

Experimental verification of facet load transmission by direct measurement of facet lamina contact pressure.

This paper presents results of a new measuring technique by means of which facet tip contact pressure data were obtained. The aim of the paper is to demonstrate by direct measurement the existence of a load transmission mechanism through the facet joint. Six lumbar spine motion segments were used in 21 tests. Simulated extensor muscle action was provided to overcome moments due to eccentric loads which represented body weight and an external hand-held load acting 340 mm anterior to the center of the disc. Facet pressure was measured in all cases when muscle load was applied to counteract body weight. This pressure increased when more muscle force was applied to balance the externally applied flexion moment. When the anterior load was released suddenly, there was a large increase in facet pressure with a concomitant decrease in disc pressure.

Localization of substance P and neurofilament immunoreactive fibers in the lumbar facet joint capsule and supraspinous ligament of the rabbit.

An indirect immunofluorescence method was utilized to identify substance P-like immunoreactive (SPLI) and neurofilament protein immunoreactive (NFIR) fibers in the lumbar facet joint capsule and supraspinous ligament of the rabbit. The results demonstrated a large population of NFIR fibers, indicating that these tissues are richly innervated, and a smaller population of SPLI fibers. In some fibers, neurofilament protein and substance P were colocalized. The data suggest that the facet joint capsule and the supraspinous ligament contain SPLI nociceptive fibers that could be a source of low back pain.