Olfactory ensheathing cells but not fibroblasts reduce the duration of autonomic dysreflexia in spinal cord injured rats.

Autonomic dysreflexia is a common complication after high level spinal cord injury and can be life-threatening. We have previously shown that the acute transplantation of olfactory ensheathing cells into the lesion site of rats transected at the fourth thoracic spinal cord level reduced autonomic dysreflexia up to 8weeks after spinal cord injury. This beneficial effect was correlated with changes in the morphology of sympathetic preganglionic neurons despite the olfactory cells surviving no longer than 3weeks. Thus the transitory presence of olfactory ensheathing cells at the injury site initiated long-term functional as well as morphological changes in the sympathetic preganglionic neurons. The primary aim of the present study was to evaluate whether olfactory ensheathing cells survive after transplantation within the parenchyma close to sympathetic preganglionic neurons and whether, in this position, they still reduce the duration of autonomic dysreflexia and modulate sympathetic preganglionic neuron morphology. The second aim was to quantify the density of synapses on the somata of sympathetic preganglionic neurons with the hypothesis that the reduction of autonomic dysreflexia requires synaptic changes. As a third aim, we evaluated the cell type-specificity of olfactory ensheathing cells by comparing their effects with a control group transplanted with fibroblasts. Animals transplanted with OECs had a faster recovery from hypertension induced by colorectal distension at 6 and 7weeks but not at 8weeks after T4 spinal cord transection. Olfactory ensheathing cells survived for at least 8weeks and were observed adjacent to sympathetic preganglionic neurons whose overall number of primary dendrites was reduced and the synaptic density on the somata increased, both caudal to the lesion site. Our results showed a long term cell type-specific effects of olfactory ensheathing cells on sympathetic preganglionic neurons morphology and on the synaptic density on their somata, and a transient cell type-specific reduction of autonomic dysreflexia.

Assessment of corneal curvature using verion optical imaging system: a comparative study.

BACKGROUND: Keratometry is a critical determinant of the postoperative refractive outcome. This study evaluates the comparability of keratometry measurements obtained using the Verion Optical Imaging System with devices used in current clinical practice. Further, it determines the interobserver reliability of the Verion Optical Imaging System. DESIGN: Retrospective analysis of patient data PARTICIPANTS: Keratometric data was obtained from 100 patients presenting for pre-operative evaluation. Furthermore, repeatability and reproducibility were assessed using 15 healthy volunteers. METHODS: Corneal curvature values acquired by the Verion Optical Imaging System were compared with existing keratometry devices including autokeratometry, partial coherence interferometry (IOLMaster) and Scheimpflug corneal topography (Pentacam). MAIN OUTCOME MEASURES: Direct comparison of corneal power, cylinder, axis of astigmatism and vector analysis were performed using correlation and Bland-Altman analyses. Reproducibility and reliability of the device were assessed using within-subject standard deviation and intraclass correlation coefficients for experienced and inexperienced technicians. RESULTS: There was no statistically significant difference between Verion values and those obtained by other methods in relation to mean keratometry, corneal astigmatism, steep meridian and vector analyses (P > 0.05). Bland-Altman plots showed narrow limits of agreement for keratometry and astigmatism and wider agreement for steep meridian. Intraoperator reliability for both experienced and inexperienced operators and interoperator reproducibility showed no statistically significant differences between values. CONCLUSION: Measurements show no significant difference from those obtained by the other devices. This suggests the Verion system is en par with instruments used in current clinical practice. The Verion Optical Imaging System produces repeatable data with no difference related to operator experience.

Visual snow: A thalamocortical dysrhythmia of the visual pathway?

In this paper we review the visual snow (VS) characteristics of a case cohort of 32 patients. History of symptoms and associated co-morbidities, ophthalmic examination, previous investigations and the results of intuitive colourimetry were collected and reviewed. VS symptoms follow a stereotypical description and are strongly associated with palinopsia, migraine and tinnitus, but also tremor. The condition is a chronic one and often results in misdiagnosis with psychiatric disorders or malingering. Colour filters, particularly in the yellow-blue colour spectrum, subjectively reduced symptoms of VS. There is neurobiological evidence for the syndrome of VS that links it with other disorders of visual and sensory processing such as migraine and tinnitus. Colour filters in the blue-yellow spectrum may alter the koniocellular pathway processing, which has a regulatory effect on background electroencephalographic rhythms, and may add weight to the hypothesis that VS is a thalamocortical dysrhythmia of the visual pathway.

Changes in electrical perceptual threshold in the first 6 months following spinal cord injury.

OBJECTIVES: To investigate the use of electrical perceptual threshold (EPT) testing to follow the natural history of sensory progression after complete and incomplete acute spinal cord injury (SCI) and to compare EPT changes with the American Spinal Injuries Association (ASIA) Impairment Scale (AIS). STUDY DESIGN: Prospective descriptive study. METHODS: ASIA examination and EPT testing was performed on 17 patients (7 AIS A, 10 AIS B-D), within 1, 3, and 6 months after acute SCI. EPT assessment was carried out bilaterally at ASIA sensory points from 2 levels above the neurological level to all levels below, including the sacral segments. Comparisons of EPT values above, at, and below the SCI were made at the three time points as well as comparisons of EPT data to ASIA assessment. RESULTS: There was poor agreement between lowest normal level on EPT and ASIA assessment. Over time, EPTs tended to deteriorate above and at the ASIA level in AIS A patients with modest changes below the neurological level of injury (NLI), mainly where EPTs correlated with the zone of partial preservation. Sacral sparing was detected in one patient with EPT testing, but not with ASIA assessment. AIS B-D patients showed improvement at the ASIA level and extensive changes, both improvement and deterioration, below the NLI. CONCLUSION: EPT testing has sufficient sensitivity to detect subclinical changes in sensory function as early as the first month post-SCI, which is not apparent in ASIA examination. In particular, the testing is able to show abnormalities at and around the injury site for both complete and incomplete SCI. In addition, EPT allows for the detection and monitoring of alterations, both improvements and deterioration, in the abnormal range of sensation.

Delayed olfactory ensheathing cell transplants reduce nociception after dorsal root injury.

Injury to cervical dorsal roots mimics the deafferentation component of brachial plexus injury in humans, with intractable neuropathic pain in the deafferented limb being a common consequence. Such lesions are generally not amenable to surgical repair. The use of olfactory ensheathing cells (OECs) for dorsal root repair, via acute transplantation, has been successful in several studies. From a clinical point of view, delayed transplantation of OECs would provide a more realistic timeframe for repair. In this study we investigated the effect of delayed OEC transplantation on functional recovery of skilled forepaw movements and amelioration of neuropathic pain, using a C7 and C8 dorsal root injury rat model previously established in our lab. We found that OEC transplantation to the dorsal horn 1 week after root injury effectively attenuated neuropathic disturbances associated with dorsal root injury, including spontaneous pain behavior, tactile allodynia and thermal hyperalgesia. The sensory controls of complex, goal-oriented skilled reaching and ladder walking, however, were not improved by delayed OEC transplantation. We did not detect any significant influence of transplanted OECs on injury-induced central reorganisation and afferent sprouting. The anti-nociceptive effect mediated by OEC transplants may therefore be explained by alternative mechanisms such as modification of inflammation and astrogliosis. The significant effect of OEC transplants in mitigating neuropathic pain may be clinically useful in intractable pain syndromes arising from deafferentation. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair.

Age, gender, and side differences of cutaneous electrical perceptual threshold testing in an able-bodied population.

OBJECTIVE: To investigate age, gender, and left-right differences in cutaneous electrical perceptual threshold (EPT) testing in an able-bodied, Australian sample. STUDY DESIGN: Prospective experimental. SETTING: Hospital-based spinal cord injuries unit. METHODS: Cutaneous electrical stimulation of the 28 dermatomes at ASIA sensory key points (C2-S4/S5) was performed on 29 female and 16 male healthy volunteers aged 21 to 76 years. Mean EPTs for each dermatome were compared (repeated measures ANOVA) for left-right, gender-related, and age-related (50 years of age) differences. RESULTS: There was no group difference between sides (repeated measures ANOVA, P = 0.934). Women across all ages had lower group mean EPTs than men (P < 0.0001). Women younger than age 50 years had lower mean EPTs than those older than age 50 years (P = 0.008). There was no group difference between younger and older men (P = 0.371). Analysis of individual dermatomes revealed no significant differences in thoracic dermatomes between genders or age groups, contrary to the limb dermatomes. CONCLUSION: There were gender differences in EPT values across all ages. Women had higher EPTs as they advanced in age, but this was less clear in men. There was considerable somatotopic variability in EPTs, especially in the lower limbs. If EPT testing is to be applied to detect subclinical changes within a dermatome, establishment of age- and gender-specific somatotopic normograms is a prerequisite.

Compensatory mechanisms to maintain blood pressure in paraplegic rats: implication of central tachykinin NK-1 and NK-3 receptors?

People with high level spinal cord injury (SCI) suffer from both hypotension and spontaneous hypertension due to loss of supraspinal control of spinal sympathetic outflow. Few reports have addressed whether any changes occur in central regulation of blood pressure (BP) and heart rat (HR) at the supraspinal level. Central tachykinin NK-1 and NK-3 receptors are located in many cardiovascular areas in the brain and are known to modulate BP and HR. This study examined the intracerebroventricular (i.c.v.) effects of the selective NK-1 receptor agonist [Sar(9), Met(O(2))(11)]SP (65pmol, n=6) and NK-3 receptor agonist senktide (650pmol, n=6) on mean arterial pressure (MAP) and HR before and after complete spinal cord transection at thoracic level 4 (T4). [Sar(9), Met(O(2))(11)]SP evoked increases in MAP and HR which were still present 4days after the T4 SCI. Further analysis using the beta(1)-adrenoceptor antagonist atenolol (10mgkg(-1)) revealed an increased contribution of HR in the MAP increase after SCI. For senktide, 2 and 5weeks after T4 SCI, the rise in MAP induced by senktide was significantly increased in magnitude and was similar to a normal response at 8weeks. These effects were accompanied by a bradycardia, which was still present and amplified at 8weeks. Our results reveal a transient potentiation of the senktide-mediated MAP effect and a greater contribution of the HR in MAP increase by [Sar(9), Met(O(2))(11)]SP in T4 transected rats. Although the significance of these changes remains to be established. This suggest a reorganization of supraspinal mechanisms regulating BP and HR after a high level SCI. Central NK-1 and NK-3 receptors might therefore contribute to the maintenance of MAP following high thoracic SCI.

Characterization of rat forepaw function in two models of cervical dorsal root injury.

Dorsal root injury (DRI) disrupts afferent input from the periphery and often leads to sensory deficits and neuropathic pain. Despite cervical root injuries in rodents being a useful model for deafferentation studies, a quantitative characterization of the sensory deficits produced by DRI is still lacking. This study aimed to characterize the different functional deficits resulting from a dorsal two- or four-root (C7-C8 and C5-C8, respectively) crush injury in rats at levels that innervate the forepaws. The impairment of the affected forepaw was assessed by mechanical and thermal pain responses, and rating the performance on the skilled reaching and ladder rung walking tests (LRWT). Postoperatively, only the two-root DRI rats developed mechanical allodynia, which persisted throughout the course of the study. Thermal hyperalgesia peaked at weeks 1 and 6. The four-root DRI animals were less sensitive to mechanical and thermal stimulation. Performance on the skilled reaching task could only be measured in two-root DRI rats, as animals with four-root injury were unable to grasp the pellets at all. On the LRWT, gait impairment was proportional to the severity of the lesion, with four-root DRI animals showing a significantly higher rate of errors than two-root DRI animals. These results suggest that two-root DRI represents a good model to assess treatments for allodynia-induced neuropathic pain, and for the restoration of the sensory component of the skilled motor performance. On the other hand, the four-root DRI would be a useful model when forepaw deafferentation is required.