Cardiovascular and renin responses to head-up tilt tests in parkinsonism

Objectives - We investigated cardiovascular and renin responses to head-up tilt tests in patients with Parkinson's disease (PD), multiple system atrophy (MSA), and in controls to determine variables for the assignment of parkinsonism to the potential underlying neurologic condition. Patients and methods - Sequential changes in sympathetic-mediated circulatory variables such as heart rate, blood pressure, and plasma renin concentration during head-up tilt tests were studied in 14 patients with PD and 11 patients with MSA. Twelve subjects with normal autonomic functions were studied as controls. Results - Head-up tilt resulted in significant differences in blood pressure and heart rate responses between PD, MSA, and controls. The baseline plasma renin concentration was significantly lower in MSA than in controls. Twenty min head-up tilt revealed significant differences in plasma renin concentration between PD, MSA, and controls. Conclusion - We conclude that investigating sequential changes in mean arterial blood pressure, heart rate, and plasma renin concentration during head-up tilt test can potentially support differential diagnosis of PD and MSA.     

Autonomic responses to carbohydrate ingestion and head-up tilt in elderly subjects with orthostatic hypotension

To investigate the role of glucose and insulin in the development of hypotension following glucose ingestion in elderly subjects with orthostatic hypotension, the autonomic responses to glucose and xylose ingestion were studied in five elderly subjects with age related orthostatic hypotension (without autonomic failure), five elderly control subjects and three elderly subjects with evidence of autonomic failure. Heart rate, blood pressure, plasma noradrenaline and plasma arginine vasopressin responses to glucose ingestion and to xylose ingestion were investigated. All subjects were supine for 90 min following ingestion of each carbohydrate and were then tilted 45° head-up for 10 min. Blood pressure was maintained in elderly control subjects following ingestion of both carbohydrates and during tilting. The elderly group with orthostatic hypotension, while supine had a fall in systolic blood pressure 60–90 min following both glucose and xylose ingestion. Diastolic blood pressure was lowered 60–90 min after glucose but not xylose. During tilting, blood pressure fell by similar levels following both carbohydrate ingestions; plasma noradrenaline levels after 2 min and plasma arginine vasopressin levels after 10 min tilting were significantly less following glucose ingestion compared to xylose ingestion. The autonomic failure group while supine had a fall in systolic blood pressure 60–90 min following both glucose and xylose ingestion. Diastolic blood pressure was lowered 60–90 min after glucose but not xylose. During tilting, blood pressure fell by similar levels following both carbohydrate ingestion. Plasma noradrenaline and arginine vasopressin levels were unchanged after ingestion of either carbohydrate, and during tilting. These results suggest that hypotension following glucose ingestion in elderly subjects with orthostatic hypotension, but without efferent autonomic failure may be due, in part, to impaired afferent or central baroreceptor reflexes.     

Reaction of spinal cord central canal cells to cord transection and their contribution to cord regeneration

After transection, the spinal cord of the eel Anguilla quickly regrows and reconnects, and function recovers. We describe here the changes in the central canal region that accompany this regeneration by using serial semithin plastic sections and immunohistochemistry. The progress of axonal regrowth was followed in material labeled with DiI. The canal of the uninjured cord is surrounded by four cell types: S-100-immunopositive ependymocytes, S-100- and glial fibrillary acidic protein (GFAP)-immunopositive tanycytes, vimentin-immunopositive dorsally located cells, and lateral and ventral liquor-contacting neurons, which label for either gamma-aminobutyric acid (GABA) or tyrosine hydroxylase (TH). After cord transection, a new central canal forms rapidly as small groups of cells at the leading edges of the transection create flat "plates" that serve as templates for subsequent formation of the lateral and dorsal walls. Profile counts and 5-bromo-2'-deoxyuridine immunohistochemistry indicate that these cells are dividing rapidly during the first 20 days of the repair process. The newly formed canal, which bridges the transection by day 10 but is not complete until about day 20, is greatly enlarged (相似文献   

Enhanced pressor response to noradrenaline in patients with cervical spinal cord transection.

Arterial blood pressure, heart-rate and the electrocardiogram were recorded in subjects tetraplegic from cervical spinal cord transections, and in control subjects, before, during and after intravenous infusions of 1-noradrenaline. Over a wide range of doses the blood pressure rose much more in the tetraplegics than in the controls. Circulating noradrenaline during infusion did not significantly differ between the two groups. The findings indicate that tetraplegic subjects have an enhanced pressor response to noradrenaline infusions. Such a response therefore does not necessarily indicate post-ganglionic sympathetic denervation. The observed responses in the tetraplegics may in part be due to exaggerated adrenergic receptor responses, but the main cause is likely to be the loss of those baroreceptor reflexes with sympathetic efferent pathways.     

Axonal regeneration after spinal cord transection and reconstruction

Following complete transection of the spinal cord, cats were separated into 2 groups to undergo: (i) surgical reconstruction of the disconnected cord using a neuroactive agent mixed into a collagen matrix bridge and omental transposition and (ii) cord transection-only. After 90 days, animals were killed and the brain and spinal cord were removed for immunohistochemistry. Two weeks prior to sacrifice, spinal cord blood flows were measured and the retrograde axonal tracer Fluoro-Gold was injected below the transection site. Gross inspection of the spinal cords at autopsy showed excellent integration and continuity of the collagen matrix bridge with the proximal-distal stumps in the surgical reconstruction group. In the transection-only group, the proximal-distal stumps were connected by a fibrotic, often tapered in the middle, tissue bridge. Results show that omental transposition in the surgical reconstruction group increased spinal cord blood flow by 58% when compared to transection-only animals. Fluoro-Gold was found in mesencephalic and brainstem catecholaminergic and cholinergic neurons known to send axons to the spinal cord. Immunohistochemical staining with antibodies against catecholamine synthesizing enzymes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) showed that surgical reconstruction treated cat cords but not transection-only, developed dense bundles of dopaminergic and noradrenergic fibers which were present in the collagen matrix bridge and in the distal spinal cord. Extension of these catecholaminergic fibers in surgical reconstruction treated cats showed maximal outgrowth of 90 mm below the transection site when the neuroactive agent 4-aminopyridine was mixed into the collagen matrix. In addition, the synaptogenic marker synaptophysin (SYN) was observed on preganglionic sympathetic neurons in association with dopaminergic- and noradrenergic-containing varicosities distal to the collagen matrix bridge, an indication that neo-synaptic contacts may have been made on these previously denervated neurons. No TH, DBH or SYN was observed below the transection site in transection-only cats. These findings indicate that surgical reconstruction treated cords can develop dense supraspinal fiber outgrowth across a treated collagen matrix bridge fed by an omental blood supply and that these fibers may have made neo-synaptic contacts with appropriate distal spinal cord target tissue.     

Passive exercise and fetal spinal cord transplant both help to restore motoneuronal properties after spinal cord transection in rats

Spinal cord transection influences the properties of motoneurons and muscles below the lesion, but the effects of interventions that conserve muscle mass of the paralyzed limbs on these motoneuronal changes are unknown. We examined the electrophysiological properties of rat lumbar motoneurons following spinal cord transection, and the effects of two interventions shown previously to significantly attenuate the associated hindlimb muscle atrophy. Adult rats receiving a complete thoracic spinal cord transection (T-10) were divided into three groups receiving: (1) no further treatment; (2) passive cycling exercise for 5 days/week; or (3) acute transplantation of fetal spinal cord tissue. Intracellular recording of motoneurons was carried out 4-5 weeks following transection. Transection led to a significant change in the rhythmic firing patterns of motoneurons in response to injected currents, as well as a decrease in the resting membrane potential and spike trigger level. Transplants of fetal tissue and cycling exercise each attenuated these changes, the latter having a stronger effect on maintenance of motoneuron properties, coinciding with the reported maintenance of structural and biochemical features of hindlimb muscles. The mechanisms by which these distinct treatments affect motoneuron properties remain to be uncovered, but these changes in motoneuron excitability are consistent with influences on ion conductances at or near the initial segment. The results may support a therapeutic role for passive limb manipulation and transplant of stem cells in slowing the deleterious responses of motoneurons to spinal cord injury, such that they remain more viable for subsequent alternative strategies.     

Axonal regrowth after spinal cord transection in adult zebrafish

Using axonal tracers, we characterized the neurons projecting from the brain to the spinal cord as well as the terminal fields of ascending spinal projections in the brain of adult zebrafish with unlesioned or transected spinal cords. Twenty distinct brain nuclei were found to project to the spinal cord. These nuclei were similar to those found in the closely related goldfish, except that additionally the parvocellular preoptic nucleus, the medial octavolateralis nucleus, and the nucleus tangentialis, but not the facial lobe, projected to the spinal cord in zebrafish. Terminal fields of axons, visualized by anterograde tracing, were seen in the telencephalon, the diencephalon, the torus semicircularis, the optic tectum, the eminentia granularis, and throughout the ventral brainstem in unlesioned animals. Following spinal cord transection at a level approximately 3.5 mm caudal to the brainstem/spinal cord transition zone, neurons in most brain nuclei grew axons beyond the transection site into the distal spinal cord to the level of retrograde tracer application within 6 weeks. However, the individually identifiable Mauthner cells were never seen to do so up to 15 weeks after spinal cord transection. Nearly all neurons survived axotomy, and the vast majority of axons that had grown beyond the transection site belonged to previously axotomized neurons as shown by double tracing. Terminal fields were not re-established in the torus semicircularis and the eminentia granularis following spinal cord transection. J Comp Neurol 377:577–595, 1997. © 1997 Wiley-Liss, Inc.     

The neuroglial response to injury following spinal cord transection in the goldfish

The spinal cord of nine goldfish was transected and studied 3 months later with conventional histological stains and by immunofluorescence with antibodies to the glial fibrillary acidic protein, a brain specific protein in fibrous astrocytes. In five fish complete transection had been followed by axonal regeneration, while in two fish the proximal and distal stumps had failed to reunite and were separated by bone, cartilage and fibrous tissue. In the remaining two goldfish the transection was incomplete. Neuroglial fibers were scanty or altogether absent in the regenerated portion of the spinal cord. Fibrous gliosis was observed in the spinal cord close to the transection, but it was extremely variable in severity in different fish and in the same fish at different levels. No fibrous gliosis was present in the descending tracts.     

Histological and hormonal testicular changes in spinal cord patients

Hormonal dosages and testicular biopsy are discussed in paraplegic patients of several neurological levels. There are no absolute biological criteria but histology showed slowing of spermatogenesis.     

Gentamicin disposition kinetics in humans with spinal cord injury

The disposition kinetics of gentamicin, an aminoglycoside antibiotic, were studied in seven tetraplegic and six paraplegic volunteers. The volume of distribution of gentamicin in l/kg of body weight varied in a statistically significant way from values of this parameter measured in normal subjects. The elimination of gentamicin in spinal man proceeded in a log-linear fashion accurately characterized by a one compartment open-model with a half-life of approximately 2 hours. The clinical significance of altered disposition kinetics and an increased intersubject variability in gentamicin disposition in spinal man as compared to normal subjects is unknown. The existence of these observed differences in pharmacokinetic parameters, however, emphasizes the need to define individual pharmacokinetic profiles and individualize dosing regimens in spinal man. The data presented are supportive of the hypothesis that spinal man constitutes a discreet therapeutic population.     

Cardiovascular responses to cocaine placebo in humans: a preliminary report

Cardiovascular responses after placebo-cocaine injections were in the same direction as the effect of cocaine iv in 22 male volunteers. Subjects received iv placebo in a room where they had been given repeated doses of iv cocaine. The placebo response consisted of an increase from baseline values of systolic and diastolic blood pressure and pulse rate. The control group, 8 subjects, which was not exposed to a conditioning phase, showed a smaller increase in the pulse rate and systolic blood pressure after the placebo injection. The results, in accordance with animal literature, suggest the existence of cocaine-conditioned effects in humans.     

Noradrenergic innervation of the rat spinal cord caudal to a complete spinal cord transection: Effects of olfactory ensheathing glia

Transplantation of olfactory bulb-derived olfactory ensheathing glia (OEG) combined with step training improves hindlimb locomotion in adult rats with a complete spinal cord transection. Spinal cord injury studies use the presence of noradrenergic (NA) axons caudal to the injury site as evidence of axonal regeneration and we previously found more NA axons just caudal to the transection in OEG- than media-injected spinal rats. We therefore hypothesized that OEG transplantation promotes descending coeruleospinal regeneration that contributes to the recovery of hindlimb locomotion. Now we report that NA axons are present throughout the caudal stump of both media- and OEG-injected spinal rats and they enter the spinal cord from the periphery via dorsal and ventral roots and along large penetrating blood vessels. These results indicate that the presence of NA fibers in the caudal spinal cord is not a reliable indicator of coeruleospinal regeneration. We then asked if NA axons appose cholinergic neurons associated with motor functions, i.e., central canal cluster and partition cells (active during fictive locomotion) and somatic motor neurons (SMNs). We found more NA varicosities adjacent to central canal cluster cells, partition cells, and SMNs in the lumbar enlargement of OEG- than media-injected rats. As non-synaptic release of NA is common in the spinal cord, more associations between NA varicosities and motor-associated cholinergic neurons in the lumbar spinal cord may contribute to the improved treadmill stepping observed in OEG-injected spinal rats. This effect could be mediated through direct association with SMNs and/or indirectly via cholinergic interneurons.     

Neurogenesis in the lamprey central nervous system following spinal cord transection

After spinal cord transection, lampreys recover functionally and axons regenerate. It is not known whether this is accompanied by neurogenesis. Previous studies suggested a baseline level of nonneuronal cell proliferation in the spinal cord and rhombencephalon (where most supraspinal projecting neurons are located). To determine whether cell proliferation increases after injury and whether this includes neurogenesis, larval lampreys were spinally transected and injected with 5‐bromo‐2&prime‐deoxyuridine (BrdU) at 0–3 weeks posttransection. Labeled cells were counted in the lesion site, within 0.5 mm rostral and caudal to the lesion, and in the rhombencephalon. One group of animals was processed in the winter and a second group was processed in the summer. The number of labeled cells was greater in winter than in summer. The lesion site had the most BrdU labeling at all times, correlating with an increase in the number of cells. In the adjacent spinal cord, the percentage of BrdU labeling was higher in the ependymal than in nonependymal regions. This was also true in the rhombencephalon but only in summer. In winter, BrdU labeling was seen primarily in the subventricular and peripheral zones. Some BrdU‐labeled cells were also double labeled by antibodies to glial‐specific (antikeratin) as well as neuron‐specific (anti‐Hu) antigens, indicating that both gliogenesis and neurogenesis occurred after spinal cord transection. However, the new neurons were restricted to the ependymal zone, were never labeled by antineurofilament antibodies, and never migrated away from the ependyma even at 5 weeks after BrdU injection. They would appear to be cerebrospinal fluid‐contacting neurons. J. Comp. Neurol. 522:1316–1332, 2014. © 2013 Wiley Periodicals, Inc.     

Blood-spinal cord barrier disruption proximal to a spinal cord transection in the rat: time course and pathways associated with protein leakage

The effects of spinal cord transection on the blood-spinal cord barrier of the rat were examined at the ultrastructural level at sites 0.5 and 1.0 cm proximal to the injury. Using the vascular tracer horseradish peroxidase (HRP), the time course and pathways of barrier disruption were evaluated. At 0.5 cm, barrier disruption was noted from as early as 15 min and continued to 12 h after injury, whereas at 1.0 cm, evidence for vascular permeability was confined to between 15 min and 3 h. The presence of barrier breakdown to exogenous protein at a distance from the transection emphasizes that injury promotes a more generalized vascular response which likely contributes to subsequent edematous changes. The mechanism(s) involved in increased permeability appears to be primarily related to transendothelial vesicular transport of the tracer. There was no evidence for interendothelial leakage of the tracer across compromised tight junctions. In comparing these findings with those reported on sites distal to a transection, it is clear that there is an asymmetry in the vascular response to HRP. The pinocytotic index, an indicator of endothelial uptake of HRP, was significantly elevated (compared with control) distal to a transection from 3 h through 3 days after injury, attaining a maximum at 12 h. In contrast, the pinocytotic index proximal to a transection was significantly elevated compared to control values at only 1 h after injury. Furthermore, at 3 h after injury, when barrier disruption was most prominent, there was a smaller percentage of vessels exhibiting leakage to HRP proximal as opposed to distal to a transection.     

Postcordotomy spontaneous dysesthesias in macaques: recurrence after spinal cord transection

Monkeys chronically attack the hypoalgesic hindlimb after thoracic contralateral anterolateral cordotomy or hemisection. This compulsive behavior could be induced by innocuous stimulation in the hypoalgesic region, and it also appeared to occur spontaneously. The postcordotomy spontaneous compulsive self-directed behavior was studied in 4 macaques after subsequent upper lumbar crush spinal transection. Despite the paraplegia and bilateral analgesia/anesthesia, this spontaneous abnormal behavior continued to be directed to the same hindlimb as before transection, but not to the opposite hindlimb. Hence, it is concluded that the recurring syndrome originated from the initial contralateral cordotomy. The rationale for the presumption of postcordotomy spontaneous dysesthesias is presented, and the experimental results are offered in refutation of alternative interpretive hypotheses. In conjunction with previous findings, these results lead to the argument that postcordotomy dysesthesias are caused by a neuropathological compensatory response to partial deafferentation of brain somatosensory neurons.