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Magnetic resonance imaging in the diagnosis of lymphoma involving the brachial plexus in a cat.

An 11-year-old, neutered, female Domestic Long Hair cat had a 3-week history of left forelimb lameness. Conscious proprioception and postural reflexes were absent on the left thoracic limb. The cat had slightly reduced placing and hopping responses on the left pelvic limb, absent cutaneous trunci muscle reflex on the left side, and left triceps muscle atrophy. Magnetic resonance imaging revealed a 2 x 2 x 2 cm mass in the region of the left brachial plexus. The cat was treated by left forelimb amputation and hemilaminectomy. Histopathology of the brachial plexus revealed lymphoma.

Animals↗

Neuroaxonal dystrophy in a litter of papillon pups.

A litter of five 14-week-old papillon puppies was referred for investigation of pelvic limb ataxia. Clinical examination revealed signs of ataxia, hypermetria and depressed postural reflexes affecting all four limbs. The severity of these signs varied between members of the litter. The condition became progressively worse and by 19 weeks of age all but the least severely affected pup (the single male of the litter) had deteriorated to the point that euthanasia was indicated on humane grounds. Pathological examination revealed widespread changes in both white and grey matter of the neuraxis caudal to the forebrain, particularly involving the dorsolateral white matter of the spinal cord, which were characterised by axonal swellings typical of neuroaxonal dystrophy.

Animals↗

Description of Parkinson's disease as a clinical syndrome.

Parkinsonism is a clinical syndrome comprising combinations of motor problems-namely, bradykinesia, resting tremor, rigidity, flexed posture, "freezing," and loss of postural reflexes. Parkinson's disease (PD) is the major cause of parkinsonism. PD is a slowly progressive parkinsonian syndrome that begins insidiously and usually affects one side of the body before spreading to involve the other side. Pathology shows loss of neuromelanin-containing monoamine neurons, particularly dopamine (DA) neurons in the substantia nigra pars compacta. A pathologic hallmark is the presence of cytoplasmic eosinophilic inclusions (Lewy bodies) in monoamine neurons. The loss of DA content in the nigrostriatal neurons accounts for many of the motor symptoms, which can be ameliorated by DA replacement therapy-that is, levodopa. Most cases are sporadic, of unknown etiology; but rare cases of monogenic mutations (10 genes at present count) show that there are multiple causes for the neuronal degeneration. The pathogenesis of PD remains unknown. Clinical fluctuations and dyskinesias are frequent complications of levodopa therapy; these, as well as some motor features of PD, improve by resetting the abnormal brain physiology towards normal by surgical therapy. Nonmotor symptoms (depression, lack of motivation, passivity, and dementia) are common. As the disease progresses, even motor symptoms become intractable to therapy. No proven means of slowing progression have yet been found.

Animals↗

Differential effect of nerve injury at birth on the activity pattern of reinnervated slow and fast muscles of the rat.

The activity patterns of the reinnervated slow soleus and fast extensor digitorum longus (e.d.l.) muscles were studied in rats during the first 6 months after sciatic nerve crush at birth, using chronic electromyography. When the nerve lesion was inflicted shortly after birth, the recovery of the muscle weight and size was always much less than if the same lesion was inflicted on adult animals. As previously demonstrated, this effect is due to motoneurone and muscle fibre loss. Following reinnervation after a neonatal crush, the soleus muscle recovered its normal tonic activity pattern during postural and spontaneous locomotor activity. By contrast, in the reinnervated e.d.l. muscle, abnormal tonic motor unit activity was recorded during locomotion, in addition to the phasic activity characteristic of the normal muscle. In response to postural reflexes elicited by tilting the animal, tonic motor unit activity was recorded from the reinnervated e.d.l. muscle, whereas the normal muscle was not activated by these stimuli. The aggregate activity recorded from the reinnervated e.d.l. during spontaneous locomotion was about 2-3 times greater than normal, whereas in the reinnervated soleus no significant change took place. In animals which had their nerves crushed as adults, the activity pattern and aggregate activity of both muscles was similar to normal. The firing pattern of individual motor units from normal and reinnervated muscles was compared. After a neonatal crush, the mean frequency of firing of e.d.l. motor units was significantly lower compared to normal or to that after an adult crush, whereas in soleus no significant change was found. These results indicate that peripheral nerve lesions during early development affect predominantly the development of motoneurones with a phasic, high-frequency discharge pattern resulting in a shift towards tonic, lower-frequency motor unit activity.

Action Potentials↗

Urinary function in elderly people with and without leukoaraiosis: relation to cognitive and gait function.

OBJECTIVES: To investigate urinary function in the elderly with and without white matter lesion (leukoaraiosis) in relation to cognitive and gait function. METHODS: Sixty three subjects were examined, with mean age 73 (range 62 to 86 years). Subjects with brainstem stroke or with large hemispheric lesions were excluded. Spin echo 1.5 T MRI images were graded from 0 to 4 for severity of white matter lesions. Urinary function was assessed by detailed questionnaire and urodynamic studies were performed in 33 of the subjects, including measurement of postmicturition residuals, water cystometry, and sphincter EMG. A mini mental state examination (MMSE) and examination of gait was also performed and compared with urinary function. RESULTS: Urodynamic studies showed subjects with grade 1-4 white matter lesions to have detrusor hyperreflexia more commonly (82%) than those with grade 0 white matter lesions (9%) (p<0.05), indicating that leukoaraiosis was a factor associated with geriatric urinary dysfunction. Postmicturition residuals, low compliance, detrusor-sphincter dyssynergia, and uninhibited sphincter relaxation were also more common in grade 1-4 than in grade 0 white matter lesions, though the difference was not significant. In grade 1 white matter lesions urinary dysfunction (urge urinary incontinence) was more common than cognitive (MMSE<19) (p<0.05) and gait disorders (slowness, short step/festination, and loss of postural reflex) (p<0. 05), which increased together with the grade of white matter lesions (p<0.05). CONCLUSIONS: Urinary dysfunction is common and probably the early sign in elderly people with leukoaraiosis on MRI.

Aged↗

Parkinsonism and occupational exposure to pesticides.

OBJECTIVE: To examine the risk of parkinsonism related to lifetime occupational exposure to pesticides among a cohort of men, mostly orchardists, in Washington State. METHODS: All 310 subjects in this study had previously participated in a cohort study of men occupationally exposed to pesticides. Subjects were given a structured neurological examination and completed a self administered questionnaire which elicited detailed information on pesticide (insecticide, herbicide, and fungicide) use throughout their working careers. Demographic characteristics were also sought. Subjects had a mean age of 69.6 years (range 49-96, SD 8.1). There were 238 (76.8%) subjects who reported some occupational exposure to pesticides, whereas 72 (23.2%) reported none. Parkinsonism was defined by the presence of two or more of rest tremor, rigidity, bradykinesia, and impairment of postural reflexes in subjects not on antiparkinsonian medication, or the presence of at least one sign if they were on such medication. Parkinson's disease was not studied explicitly because of the difficulty in distinguishing it from other parkinsonian syndromes. A generalised linear model was used to estimate prevalence ratios (PRs) for parkinsonism relative to history of farming, pesticide use, and use of well water. RESULTS: A PR of 2.0 (95% confidence interval (95% CI) 1.0 to 4.2) was found for subjects in the highest tertile of years of exposure to pesticides; a similarly increased, non-significant, PR was found for the middle tertile (1.9 (95% CI 0.9 to 4.0)), although a trend test did not show a significant exposure-response relation. No increased risks were found associated with specific pesticides or pesticide classes, nor with a history of farming or use of well water. CONCLUSION: Parkinsonism may be associated with long term occupational exposure to pesticides, although no associations with specific pesticides could be detected. This finding is consistent with most of the publications on this topic.

Aged↗

Effects of bromocryptine on hepatic blood volume responses to hepatic nerve stimulation in cats.

Arterial pressures, portal pressures, and hepatic blood volumes were recorded after hepatic denervation in cats anesthetized with pentobarbital. Bromocryptine (50 micrograms/kg) lowered arterial pressure but did not significantly change portal pressure or hepatic blood volume. However, both portal pressure and hepatic blood volume responses to hepatic nerve stimulation were significantly depressed after bromocryptine especially at low frequencies of stimulation. Responses to intraportal infusions of norepinephrine were significantly impaired only at the highest dose. The inhibitory effect of bromocryptine on the neural responses may, therefore, involve a presynaptic inhibition of norepinephrine release, but the mechanism requires further study. These data provide further support for the hypothesis that drugs which impair hepatic venous responses to sympathetic stimuli cause significant impairment of postural reflexes and orthostatic hypotension during clinical use.

Animals↗

Teaching human cardiovascular and respiratory physiology with the station method.

We have developed a station method to offer combined cardiovascular and respiratory physiology exercises all in one laboratory period during our medical physiology course. This laboratory was designed for first-year medical students in order to minimize equipment costs, maximize efficient use of both student and faculty time, and facilitate integration of basic cardiovascular concepts with those in respiratory physiology. We designed six stations for the students to evaluate: cardiovascular and respiratory responses to dynamic exercise, cold pressor reflex, postural influences and respiratory modulation of cardiovascular functions, forced expiratory maneuvers with inverted bell spirometers, forced expiratory maneuvers and maximal inspiratory maneuvers with electronic spirometers with and without obstruction, and respiratory muscle strength. Students worked in groups of two to four and were assessed by individual laboratory reports. Although we neglected to formally assess the impact on students of changes in laboratory design, students appeared to respond enthusiastically to the laboratory and prepared knowledgeable laboratory reports.

Cardiovascular Physiological Phenomena↗

Muscle sympathetic outflow during horizontal linear acceleration in humans.

To elucidate the effects of linear acceleration on muscle sympathetic nerve activity (MSNA) in humans, 16 healthy men were tested in a linear accelerator. Measurements of MSNA, electrocardiogram, blood pressure, and thoracic impedance were undertaken during linear acceleration. Sinusoidal linear acceleration with peak values at +/-0.10, +/-0.15, and +/-0.20 G was applied in anteroposterior (+/-G(x), n = 10) or lateral (+/-G(y), n = 6) directions. The total activity and burst rate of MSNA decreased significantly during forward, backward, left, or right linear accelerations. The total activity of MSNA decreased to 50.5 +/- 6.9, 52.5 +/- 4.4, 71.2 +/- 9.6, and 67.6 +/- 8.2% from the baselines (100%) during linear accelerations with peak values at +/-0.20 G in the four directions, respectively. These results suggest that dynamic stimulation of otolith organs in horizontal directions in humans might inhibit MSNA directly in order to quickly redistribute blood to muscles during postural reflexes induced by passive movement, which supports the concept that the vestibular system contributes to sympathetic regulation in humans.

Acceleration↗

Pattern of motor coordination underlying backward swimming in the lamprey.

The main form of locomotion in the lamprey (a lower vertebrate, cyclostome) is forward swimming (FS) based on periodical waves of lateral body flexion propagating from head to tail. The lamprey is also capable of backward swimming (BS). Here we describe the kinematical and electromyographic (EMG) pattern of BS, as well as the effects on this pattern exerted by different lesions of the spinal cord. The BS was evoked by tactile stimulation of a large area in the anterior part of the body. Swimming was attributed to the waves of lateral body undulations propagating from tail to head. The EMG bursts on the two sides alternated, and the EMG in more caudal segments led in phase the EMG in more rostral segments. Main kinematical characteristics of BS strongly differed from those of FS: the amplitude of undulations was much larger and their frequency lower. Also, the maintenance of the dorsal-side-up body orientation ascribed to vestibular postural reflexes (typical for FS) was not observed during BS. A complete transection of the spinal cord did not abolish the generation of forward-propagating waves rostral to the lesion. After a lateral hemisection of the spinal cord, the BS pattern persisted on both sides rostral to the lesion; caudal to the lesion, it was present on the intact side and reduced or abolished on the lesioned side. The role of the spinal cord in generation of different forms of undulatory locomotion (FS and BS) is discussed.

Animals↗

Spiking local interneurons as primary integrators of mechanosensory information in the locust.

A population of spiking local interneurons in the metathoracic ganglion of the locust is vigorously excited by particular sensory stimuli from the hindlegs and participates in local postural reflexes. We examined the inputs from singly innervated mechanoreceptors (hairs and campaniform sensilla) to these spiking local interneurons, to nonspiking local interneurons, and to motor neurons that are also elements of local reflex pathways. Recordings were made intracellularly from the interneurons and motor neurons and extracellularly from afferent fibers. The physiological evidence is consistent with the spiking local interneurons being excited by direct, chemically mediated synaptic inputs from the afferents. Each afferent spike is followed at a constant latency by an excitatory postsynaptic potential (EPSP) in a spiking local interneuron, even at instantaneous frequencies as high as 300 Hz. The estimated synaptic delay is 1.5 ms, similar to that measured at other presumed monosynaptic connections within the same ganglion. Cobalt stains of individual interneurons, and of the central projections of afferent fibers show that both branch within the same ventral region of neuropil. Afferents from several hairs and campaniform sensilla converge on an individual spiking local interneuron. One interneuron is shown to receive inputs from at least seven hairs and four campaniform sensilla, but these represent only a tiny fraction of the total number of such sensilla on a hindleg. Practical limitations to the number of sensilla that can be tested for each interneuron means that the degree of convergence is likely to be considerably underestimated. We found no evidence that nonspiking local interneurons or motor neurons receive direct inputs from the afferents tested. Neurons of both types are, however, affected by stimulation of individual hairs, and the resulting pattern of postsynaptic potentials (PSPs) is similar to the pattern of spikes evoked in the spiking local interneurons. We infer from the evidence presented here and elsewhere (10, 11) that the spiking local interneurons are involved in at least two types of pathways for local interactions: 1) sensory neuron-spiking local interneuron-motor neuron, and 2) sensory neuron-spiking local interneuron-nonspiking local interneuron-motor neuron. We conclude that the spiking local interneurons are major elements in the primary integration of inputs from external receptors on the hindlegs.

Animals↗

Rhythmic modulation of the responsiveness of locust sensory local interneurons by walking pattern generating networks.

1. Spiking local interneurons in the thoracic ganglia of the locust are known to process mechanosensory information from leg receptors and to contribute to postural reflexes. It is not clear, however, whether these interneurons are also involved in the control of leg movement during walking or whether their role in mediating local reflexes is phasically modulated by the walking pattern generating networks. To address these questions, intracellular recordings from spiking local interneurons in a midline population were made both in a "fictive walking" preparation reduced to isolated thoracic ganglia and in semi-intact locusts walking on a treadwheel. 2. In fictive walking (and therefore deafferented) preparations, rhythmic synaptic inputs were observed in 72% of the sampled local interneurons. These inputs resulted in a modulation of the interneurons' firing rate in phase with the centrally generated rhythm. A similar rhythmic drive was seen in spiking local interneurons recorded from semi-intact walking locusts. This drive persisted after amputation of the leg from which the interneurons received their sensory inputs. These results indicate that this population of interneurons receives inputs from central networks that participate in the generation of walking. 3. In fictive walking preparations where a hindleg was left attached to its segmental ganglion, individual local interneurons could be characterized physiologically by their receptive field properties. The central inputs were found to modulate the activity of members of all subclasses of interneurons (i.e., purely exteroceptive, purely proprioceptive, and with mixed receptive fields. The mode of modulation observed could oppose or assist the effect of sensory input expected to occur during normal walking.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Spatial alignment of rotational and static tilt responses of vestibulospinal neurons in the cat.

The responses of vestibulospinal neurons to 0.5-Hz, whole-body rotations in three-dimensional space and static tilts of whole-body position were studied in decerebrate and alert cats. The neurons' spatial properties for earth-vertical rotations were characterized by maximum and minimum sensitivity vectors (R(max) and R(min)) in the cat's horizontal plane. The orientation of a neuron's R(max) was not consistently related to the orientation of its maximum sensitivity vector for static tilts (T(max)). The angular difference between R(max) and T(max) was widely distributed between 0 degrees and 150 degrees, and R(max) and T(max) were aligned (i.e., within 45 degrees of each other) for only 44% (14/32) of the neurons. The alignment of R(max) and T(max) was not correlated with the neuron's sensitivity to earth-horizontal rotations, or to the orientation of R(max) in the horizontal plane. In addition, the extent to which a neuron exhibited spatiotemporal convergent (STC) behavior in response to vertical rotations was independent of the angular difference between R(max) and T(max). This suggests that the high incidence of STC responses in our sample (56%) reflects not only canal-otolith convergence, but also the presence of static and dynamic otolith inputs with misaligned directionality. The responses of vestibulospinal neurons reflect a complex combination of static and dynamic vestibular inputs that may be required by postural reflexes that vary depending on head, trunk, and limb orientation, or on the frequency of stimulation.

Afferent Pathways↗

Noradrenergic pharmacotherapy, intracerebral infusion and adrenal transplantation promote functional recovery after cortical damage.

The research described in this review briefly summarizes evidence that short term pharmacological enhancement of noradrenergic (NA) synaptic activity, combined with symptom relevant experience (SRE), promotes functional recovery of some symptoms of cortical damage in rat, cat and human beings even when treatment is initiated from days to weeks after injury. A summary is provided of the numerous drugs tested in rodent cortical injury models which have been proven useful for predicting beneficial or harmful effects on behavioral outcome in human stroke. The pattern of drug effects indicates a central role for NA in functional recovery. Additionally, studies of the effects of direct intraventricular infusion of monoamine neurotransmitters are reviewed and further support the hypothesized role of NA in recovery from some symptoms of cortical injury. The site of NA/SRE interaction to promote recovery from hemiplegia apparently involves the cerebellar hemisphere contralateral to the cortical injury. Microinfusions of NA into the contra- but not ipsilateral cerebellar hemisphere dramatically enhance recovery. Furthermore, like its systemic action, microinfusion of the alpha 1-NA receptor antagonist, phenoxybenzamine, reinstates hemiplegia. A "permanent" symptom of motor cortex injury in the cat is the complete loss of tactile placing contralateral to the injury which does not spontaneously recover for as long as seven years after ablation. This postural reflex is temporarily restored for 8-12 hours following amphetamine administration. However, this permanently lost reflex can be enduringly restored by transplanting catecholamine secreting adrenal tissue into the wound cavity. The experiment is reviewed in detail and involves chromaffin cell autografts into the frontal cortex ablation wound cavity producing a restoration of tactile placing for the 7-10 month duration of the study. This enduring restoration of tactile placing is considered a result of the release of catecholamines into the CNS from the grafted chromaffin cells found, by histochemical methods, surviving 7-10 months after transplant. Lastly, we attribute these delayed treatment effects to an attenuation of a diaschisis, or remote functional depression, in morphologically intact areas anatomically connected to the area of injury. The widespread reduction of glycolytic and oxidative metabolism, produced by focal cortical injury, is normalized by the same treatment which alleviates symptoms and is worsened by drugs which exacerbate deficits. These data support the hypothesis that providing SRE during a period of enhanced NA synaptic activity produces an enduring functional recovery after cortical injury by attenuating remote functional depression. This treatment for enhancing recovery is especially attractive since it is effective even when begun weeks after cortical damage.

Adrenal Glands↗

Experimental hemispherectomy and hemicerebellectomy and their influence on vestibular habituation.

The aim of the study was to estimate the influence of hemispherectomy and hemicerebellectomy on acquisition and retention of vestibular habituation in pigeons. The habituation training was performed using a rotatory test. The frequency of head nystagmus and postural reflexes was examined before and after acquisition of habituation and some days later, for the evaluation of the retention process. Our results suggested that the hemispherectomy did not inhibit the acquisition of habituation but retention of this phenomenon was shorter at that time. The hemicerebellectomy made it impossible to reveal the vestibular habituation.

Animals↗

A new model of cerebral microthrombosis in rats and the neuroprotective effect of a Rho-kinase inhibitor.

BACKGROUND AND PURPOSE: The aim of this study was to develop a new model of stroke based on endothelial damage and thrombotic occlusion in a perforating artery, leading to small cerebral infarcts and neurological deficits in rats. Moreover, the neuroprotective efficacy of fasudil, a rho-kinase inhibitor, was investigated in this model. METHODS: Fifty-six male Sprague-Dawley rats were used in the present study. Rats were anesthetized with sodium pentobarbital, and 100 microg of sodium laurate was injected into the left internal carotid artery on days 1 and 3. The thrombus induction and consequent of ischemic brain damage were examined by histopathological analyses and neurological deficit scoring in a posture reflex test. To investigate the neuroprotective effects of fasudil, 1 or 10 mg/kg was administered intraperitoneally 5 minutes after the first injection of sodium laurate and once daily thereafter on the following 2 days. RESULTS: One hour after the injection of sodium laurate, microscopic examination of phosphotungstic acid hematoxylin-stained sections (n=5) revealed that microthrombi containing fibrin strands obstructed the perforating arteries in the ipsilateral hemisphere. Under a transmission electron microscope (n=6), endothelial cells appeared exfoliated and the vascular lumen was obstructed by a thrombus composed of degranulated platelets, fibrin, leukocytes, and erythrocytes. No evidence of endothelial cell damage or thrombus could be found in the ipsilateral side of the pial artery (middle cerebral artery). Twenty-four hours after the second injection of sodium laurate (day 4), 13 of 15 rats (86.6%) showed mild to severe neurological deficits. Multiple small cerebral infarcts were observed in the hippocampus, cortex, and thalamus. Treatment with fasudil (1 and 10 mg/kg, n=15 each) resulted in a significant improvement in neurological deficits. Fasudil also significantly reduced the area of cerebral infarction. CONCLUSIONS: We present a new model of stroke in rats, in which the perforating arteries are selectively occluded by microthrombi. This model is useful to investigate the pathophysiology and treatment of small cerebral infarction, which is caused by perforating arterial occlusive diseases such as lacunar infarcts. Fasudil may be beneficial in the treatment of acute ischemic stroke.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

A comparison of long-term functional outcome after 2 middle cerebral artery occlusion models in rats.

BACKGROUND AND PURPOSE: Proven behavioral assessment strategies for testing potential therapeutic agents in rat stroke models are needed. Few studies include tasks that demand higher levels of sensorimotor and cognitive function. Because behavioral outcome and rate of recovery vary among ischemia models, there is a need to characterize and compare performance on specific tasks across models. METHODS: To this end, sensorimotor and cognitive deficits were assessed during a 5-week period after either permanent proximal middle cerebral artery occlusion (pMCAO) or permanent distal middle cerebral artery occlusion combined with a 90-minute occlusion of both common carotid arteries (dMCAO/tCCAO) in Sprague-Dawley rats. The EBST, hindlimb and forelimb placing, and cylinder tests were given at regular intervals postinjury to assess sensorimotor function. Cognitive function was assessed with a multitrial water navigation task. RESULTS: pMCAO, which caused both striatal and cortical damage, produced persistent sensorimotor and cognitive deficits. Limb placing responses and postural reflexes were impaired throughout the month of testing. A persistent bias for using the ipsilateral forelimb for wall movements in the cylinder test was observed as well as a bias for landing on the opposite forelimb. pMCAO rats were also impaired in the water navigation task. dMCAO/tCCAO, which caused only cortical damage, produced similar sensorimotor deficits, but these were greatly diminished by 2 weeks after injury. No impairment was found for water tank navigation. Correlations between forelimb placing (both models), water navigation performance (pMCAO model), and sensorimotor asymmetry (dMCAOtCCAO model) and infarct volume were observed. CONCLUSIONS: Based on the range of functions affected and stability of observed deficits, the pMCAO model appears to be preferable to the dMCAO/tCCAO model for use in assessing therapeutic agents for stroke.

Animals↗

Sensorimotor function and neuropathology five to six weeks after hypoxia-ischemia in seven-day-old rats.

Various therapeutic interventions after hypoxia-ischemia (HI) have been shown to reduce brain injury in the short-term perspective, but it remains uncertain whether such findings are accompanied by long-term functional and structural improvements. HI was induced in 7-d-old rats as follows. The left carotid artery was ligated, and the rat was exposed to 100 min of hypoxia (7.70% oxygen in nitrogen). At postnatal d 42 the rats were assessed using four sensorimotor tests. The results were correlated with the extent of brain damage expressed as volume of deficit of the left hemisphere as percent of the right hemisphere. In the grip-traction test, the time to falling was 2.2 times shorter in the HI animals compared with controls (p < 0.01). Asymmetries of limb-placing and foot-faults (p < 0.001) were detected in HI animals, and the motor function was abnormal in the postural reflex test (p < 0.001). We found a moderate correspondence between functional and neuropathologic outcome (r = 0.842, p < 0.001). A set of four easily performed sensorimotor tests is presented for the long-term evaluation of neurologic function in the 7-d-old rat model of HI.

Animals↗