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PubMed1998

Assessment of lower urinary tract functional deficit in rats with contusive spinal cord injury.

Traumatic spinal cord injury (SCI) produces lower urinary tract (LUT) dysfunction that has been studied in surgical transection models. Our aim was to assess LUT functional deficit in a clinically relevant model of incomplete SCI to investigate how partial preservation of supraspinal connections might affect LUT dysfunction. Standardized weight-drop contusion (10 g x 2.5 cm) or complete transection, was produced at T8 in female Sprague-Dawley rats. Behavioral tests were used to assess hind limb sensorimotor function at Day 1 after surgery and weekly thereafter. The urometric experiments were conducted on groups (n = 7) of uninjured rats and on injured rats during Weeks 1 and 2 after SCI (before and after spontaneous voiding was established) as well as Week 2 after a complete transection (n = 3). Under anesthesia, the bladder was continuously perfused with saline. Changes in bladder pressure and external urethral sphincter (EUS) electrical activity were monitored. The bladder was then dissected and weighed and both the bladder and spinal cord were fixed for pathoanatomical analyses. Our results indicate that several aspects of LUT dysfunction after contusive SCI were similar to transection, e.g., reduction of voiding efficiency (approximately 5% of normal value), decrease in inter-contraction interval (47%), increase in bladder capacity (8-fold), and weight (4.6-fold). One aspect appeared different from transection--partial recovery from acute bladder/sphincter dyssynergia. Because the coordination of bladder and EUS function is mediated by brainstem pathways, partial recovery of synergy after SCI was likely due to sparing of some relevant bulbospinal projections as was confirmed by retrograde transneuronal viral tracing.

Animals↗

PubMed2005

Skull fracture during infancy: a five-year follow-up.

A group of 19 children, who had received a skull fracture during infancy, were assessed at least 5 years following injury. The majority of the group (89%) had received a mild traumatic brain injury (TBI), with the remaining two (11%) having a moderate injury. The neuropsychological, academic, and psychosocial functioning of the TBI group was compared to that of 20 orthopedic subjects. The two groups were matched on the variables of gender, age, and socio-economic status. The TBI group was impaired on tests of visual attention and memory for faces. The two groups did not differ significantly on measures of language, sensorimotor functions, or visuospatial functioning. There were no statistically significant differences between the two groups on academic performance, or parent and teacher reports of psychosocial functioning. It is concluded that while there is an absence of deficits in the vast majority of functions, skull fracture in infancy can result in enduring impairment in specific cognitive skills related to the processing of complex nonverbal stimuli.

Attention↗

PubMed2001

Enoxaparin in experimental stroke: neuroprotection and therapeutic window of opportunity.

BACKGROUND AND PURPOSE: Heparin and heparinoids have long been proposed for stroke treatment. This study investigates the effect of enoxaparin (Lovenox, Clexane), a low-molecular-weight heparin, on functional outcome (neuroscore) and lesion size in stroke models with reversible and irreversible cerebral ischemia using middle cerebral artery occlusion (MCAO) in the rat. METHODS: Ischemia was induced in rats by transient occlusion for 2 hours or by permanent electrocoagulation of the left MCA. Forty-eight hours after ischemia, neurological deficit was evaluated by scoring sensorimotor functions and ischemic damage was quantified by histological evaluation of lesion volumes. RESULTS: After transient MCAO, enoxaparin at 2x1.5 mg/kg IV (2 and 24 hours after insult) significantly reduced lesion size by 30% (P<0.05) and improved neuroscore (P<0.01). This significant effect on lesion size and neuroscore was still evident when treatment was started 5 hours after insult. Administered under the same protocol with a 5 hours delay post permanent MCAO, enoxaparin reduced lesion size by 49% (P<0.05) and improved neuroscore (P<0.01). CONCLUSIONS: This study indicates that standard nonhemorrhagic doses of enoxaparin reduce ischemic damage with a wide therapeutic window. In addition to its anticoagulant properties, other properties of enoxaparin could act in synergy to explain its neuroprotective profile in ischemia. Thus clinical application of enoxaparin treatment in stroke warrants serious consideration.

Animals↗

PubMed1985

Multiple sclerosis: understanding the psychologic implications.

To effectively care for individuals with multiple sclerosis (MS) the practitioner must be able to understand the common psychologic sequellae. These include not only those engendered by the patient's reaction to the disease, but also those reflecting alterations in central nervous system function. Although research literature on MS has many pitfalls and the quality of the results is thus uneven, important psychologic aspects of MS that have been consistently reported are depression and anxiety, euphoria, often in association with some degree of dementia, denial of illness or of impairments, irritability and apathy, coexisting psychiatric disorders, and cognitive impairment, particularly involving sensorimotor function, primary memory, and conceptual ability.

Adult↗

PubMed1988

Receptor characteristics and recovery of function following kainic acid lesions and fetal transplants of the striatum. I. Cholinergic systems.

The relationship between striatal muscarinic cholinergic receptor development and locomotor activity/T-maze alternation behavior in adult female rats with kainic acid lesions (kal) and fetal transplants of the striatum (str) was examined. Kal led to a number of deficits under conditions of spontaneous locomotion, including: (1) decreased stereotypical and increased horizontal movements during spontaneous overnight locomotion, (2) decreased spontaneous alternation on a T-maze, and (3) deficits on a sensorimotor neurological exam. Lesion-induced deficits following injection with cholinergic agonists (pilocarpine)/antagonists (scopolamine) included: (1) hypoactivity on vertical activity and stereotypical activity following scopolamine injection, and (2) increased stereotypical activity and decreased horizontal activity following pilocarpine injection. Transplants differentially affected the different types of behavioral deficits. Transplants reversed some of the deficits under conditions of spontaneous locomotion, including the hyperactivity noted during the night period, but only partially reversed the sensorimotor neurological exam and had no effect on spontaneous alternations in the T-maze. The transplants did not reverse the lesion-induced deficits following scopolamine injection, but partially reversed the lesion-induced changes in locomotion following pilocarpine injection. The striatal transplants had reduced numbers of M1 but increased numbers of M2 muscarinic cholinergic receptors. Cholinergic receptor density correlated with scores on the sensorimotor functioning and alternation tasks, but not with the locomotor measures. Conversely, the cross-sectional area of the str correlated strongly with the transplant-induced recovery in the lesion group. These results suggest that the development of cholinergic receptor systems within the transplants proceeds abnormally, and that the abnormal development of the transplant may impact on the transplant's ability to remediate lesion-induced deficits.

Animals↗

PubMed1998

Intracisternal osteogenic protein-1 enhances functional recovery following focal stroke.

Osteogenic protein-1 (OP-1, BMP-7) is a member of the transforming growth factor-beta (TGF-beta) superfamily that selectively induces dendritic outgrowth from cultured neurons. We injected human recombinant OP-1 (1 or 10 micrograms) or vehicle into the cisterna magna of mature male Sprague-Dawley rats 1 and 4 days after focal cerebral infarction induced by middle cerebral artery (MCA) occlusion. OP-1 treatment was associated with a marked enhancement of recovery of sensorimotor function of the impaired forelimb and hindlimb (contralateral to infarcts) as assessed by limb placing tests. This effect appeared to be dose dependent. There was no difference in infarct volume between OP-1 and vehicle-treated rats. The mechanisms of enhanced recovery by intracisternal OP-1 may include promotion of dendritic sprouting in the intact uninjured brain.

Analysis of Variance↗

PubMed2005

Erythropoietin improves functional and histological outcome in neonatal stroke.

Neonatal stroke is a condition that leads to disability in later life, and as yet there is no effective treatment. Recently, erythropoietin (EPO) has been shown to be cytoprotective following brain injury and may promote neurogenesis. However, the effect of EPO on functional outcome and on morphologic changes in neonatal subventricular zone (SVZ) following experimental neonatal stroke has not been described. We used a transient focal model of neonatal stroke in P10 rat. Injury was documented by diffusion weighted MRI during occlusion. Immediately upon reperfusion, either EPO (5U/gm) or vehicle was administered intraperitoneally and animals were allowed to grow for 2 wk. Sensorimotor function was assessed using the cylinder rearing test and then brains were processed for volumetric analysis of the SVZ. Stroke induced SVZ expansion proportional to hemispheric volume loss. EPO treatment markedly preserved hemispheric volume and decreased the expansion of SVZ unilaterally. Furthermore, EPO treatment significantly improved the asymmetry of forelimb use following neonatal stroke. This functional improvement directly correlated with the amount of preserved hemispheric volume. These results suggest EPO may be a candidate in the treatment of neonatal stroke.

Animals↗

PubMed2006

[Irritable bowel syndrome in children].

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder that affects children and adolescents. The recent development of the Rome diagnostic criteria and brain-gut pathways have greatly advanced the field. The child with IBS is best evaluated and treated in the context of a biopsychosocial model of care to relive symptoms and disability. Additional research is needed to develop drugs to modulate abnormalities in sensorimotor function of the enteric nervous system in IBS and relive specific symptoms and to assess the proper role of these drugs in the treatment of children and adolescents.

Adolescent↗

PubMed2005

Administration of vaccinia virus complement control protein shows significant cognitive improvement in a mild injury model.

Previous studies have shown that traumatic mild brain injury in a rat model is accompanied by breakdown of the blood brain barrier and the accumulation of inflammatory cells. A therapeutic agent, vaccinia virus complement control protein (VCP), inhibits both the classic and the alternative pathways of the complement system and, in so doing, prevents cell death and inflammation. With the use of a rat mild injury model, the effects of VCP on spatial learning and memory were tested. Training in a Morris water maze consisted of a total of 16 trials over a 2-day period before rats were anesthetized and subjected to mild (1.0-1.1 atm) lateral fluid percussion injury (FPI) 3.0 mm lateral to the sagittal suture and 4.5 mm posterior to bregma. Ten microl of VCP (1.7 mg/ml) was injected into the injury site immediately after FPI. Two weeks post-FPI the rats were assessed in the Morris water maze for spatial learning and memory. Neurologic motor function tests were carried out after FPI for 14 consecutive days and again after 28 days. The Morris water maze data show that FPI plus saline-injected rats spent a significantly (P <0.05) larger amount of time in one of the incorrect quadrants than did the FPI plus VCP-injected group. Neurologic evaluations 24 hours postinjury revealed differences in sensorimotor function between groups. The results suggest that in a mild injury model, VCP influences neurologic outcome and offers some enhancement in spatial memory and learning.

Animals↗

PubMed1989

Anorectal physiology validated: a repeatability study of the motor and sensory tests of anorectal function.

Sixteen subjects (mean (s.d.) age 50.7 (12.8) years, three men) were studied on two separate occasions by two experienced investigators in random order. A standard protocol of anatomical, manometric and electrophysiological assessments of anorectal motor and sensory function was followed. No significant differences were found between the results obtained by the two investigators in the measurements of perineal descent, anal canal length, and canal resting pressure and squeeze pressure, pudendal nerve terminal motor latency, single-fibre electromyography fibre density of the external anal sphincter, and thresholds of mucosal electrosensitivity. This study shows that the standard tests of anorectal sensorimotor function are repeatable by different investigators. In addition, it suggests that comparison of data obtained in different centres using these techniques is valid.

Adult↗

PubMed2006

Persistent neurochemical and behavioral abnormalities in adulthood despite early iron supplementation for perinatal iron deficiency anemia in rats.

BACKGROUND: Iron deficiency anemia (IDA) has been associated with altered cognitive, motor, and social-emotional outcomes in human infants. We recently reported that rats with chronic perinatal IDA, had altered regional brain iron, monoamines, and sensorimotor skill emergence during early development. OBJECTIVE: To examine the long-term consequences of chronic perinatal IDA on behavior, brain iron and monoamine systems after dietary iron treatment in rats. METHODS: Sixty dams were randomly assigned to iron-sufficient (CN) or low-iron (EID) diets during gestation and lactation. Thereafter, all offspring were fed the iron-sufficient diet, assessed for hematology and behavior after weaning and into adulthood and for brain measures as adults (regional brain iron, monoamines, dopamine and serotonin transporters, and dopamine receptor). Behavioral assessments included sensorimotor function, general activity, response to novelty, spatial alternation, and spatial water maze performance. RESULTS: Hematology and growth were similar for EID and CN rats by postnatal day 35. In adulthood, EID thalamic iron content was lower. Monoamines, dopamine transporter, and dopamine receptor concentrations did not differ from CN. EID serotonin transporter concentration was reduced in striatum and related regions. EID rats had persisting sensorimotor deficits (delayed vibrissae-evoked forelimb placing, longer sticker removal time, and more imperfect grooming chains), were more hesitant in novel settings, and had poorer spatial water maze performance than CN. General activity and spatial alternation were similar for EID and CN. CONCLUSION: Rats that had chronic perinatal IDA showed behavioral impairments that suggest persistent striatal dopamine and hippocampal dysfunction despite normalization of hematology, growth and most brain measures.

Anemia, Iron-Deficiency↗

PubMed2001

Craniofacial muscle pain: review of mechanisms and clinical manifestations.

Epidemiologic surveys of temporomandibular disorders (TMD) have demonstrated that a considerable proportion of the population--up to 5% or 6%--will experience persistent pain severe enough to seek treatment. Unfortunately, the current diagnostic classification of craniofacial muscle pain is based on descriptions of signs and symptoms rather than on knowledge of pain mechanisms. Furthermore, the pathophysiology and etiology of craniofacial muscle pain are not known in sufficient detail to allow causal treatment. Many hypotheses have been proposed to explain cause-effect relationships; however, it is still uncertain what may be the cause of muscle pain and what is the effect of muscle pain. This article reviews the literature in which craniofacial muscle pain has been induced by experimental techniques in animals and human volunteers and in which the effects on somatosensory and motor function have been assessed under standardized conditions. This information is compared to the clinical correlates, which can be derived from the numerous cross-sectional studies in patients with craniofacial muscle pain. The experimental literature clearly indicates that muscle pain has significant effects on both somatosensory and craniofacial motor function. Typical somatosensory manifestations of experimental muscle pain are referred pain and increased sensitivity of homotopic areas. The craniofacial motor function is inhibited mainly during experimental muscle pain, but phase-dependent excitation is also found during mastication to reduce the amplitude and velocity of jaw movements. The underlying neurobiologic mechanisms probably involve varying combinations of sensitization of peripheral afferents, hyperexcitability of central neurons, and imbalance in descending pain modulatory systems. Reflex circuits in the brain stem seem important for the adjustment of sensorimotor function in the presence of craniofacial pain. Changes in somatosensory and motor function may therefore be viewed as consequences of pain and not factors leading to pain. Implications for the diagnosis and management of persistent muscle pain are discussed from this perspective.

Afferent Pathways↗

PubMed2002

A discovery of new features of gastropod local field potentials by application of wavelet tools.

Odor input evokes characteristic, time-evolving (non-stationary) events in the spontaneously active central ganglia of the snail Helix pomatia. Assuming stationarity for the signals, one could, as the first approach, apply the Fourier-based methods, frequency amplitude characteristics (FAC) measures, for analyzing such events. We could thus for the first time describe such events in frequency and amplitude and show that the frequency, at which power increases most, is specific to the odor or its class [Comp. Biochem. Physiol. 123A (1999a) 95; Comp. Biochem. Physiol. 124A (1999b) 297]. Wavelet tools assume no record stationarity and are suitable for describing the dynamically evolving brain electrical signals precisely and quantitatively. We, therefore, tested these tools for the typical odor experiments with the procerebrum (PC), the pedal ganglion (PG) and the visceral ganglion (VG) of the Helix, which we earlier analyzed by the FAC measures and compared both results. The two basic findings of the present wavelet analysis are as follows: (i) the wavelet energy fluctuations clearly visualize dynamical interactions among the major bands (0.1-3.1 Hz), implying a possible 'mutual exclusion' between slow components < 0.8 Hz and faster ones > 0.8 Hz. (ii) Entropy behavior was characteristically different for each of the three brain regions. Only in PC the response to aversive odorants (decrease of entropy = more ordered state) is differentiated in entropy from that to attractive ones (increase of entropy=more disordered or more complexly ordered state) indicating the odor-discriminating function of this region. In VG entropy of the intrinsic activity is so high (highly disordered state) due to the strong wideband activity reaching > 50 Hz that odor stimulation results mainly in lowering of entropy (= more ordered state) regardless of the nature of the odor. In PG, however, odor presentation generally increases entropy due to the robust, wide-band activation at > 3 Hz (sensorimotor function) that is generated as a secondary, but dominant and robust, response. In respect to describing time evolution of different frequency band components the present wavelet tools can much more sensitively do so, as compared with the FAC measures. They can also characterize a change in the neuroelectrical state in terms of entropy.

Animals↗

PubMed2006

Tissue sparing and functional recovery following experimental traumatic brain injury is provided by treatment with an anti-myelin-associated glycoprotein antibody.

Axonal injury is a hallmark of traumatic brain injury (TBI) and is associated with a poor clinical outcome. Following central nervous system injury, axons regenerate poorly, in part due to the presence of molecules associated with myelin that inhibit axonal outgrowth, including myelin-associated glycoprotein (MAG). The involvement of MAG in neurobehavioral deficits and tissue loss following experimental TBI remains unexplored and was evaluated in the current study using an MAG-specific monoclonal antibody (mAb). Anesthetized rats (n=102) were subjected to either lateral fluid percussion brain injury (n=59) or sham injury (n=43). In surviving animals, beginning at 1 h post-injury, 8.64 microg anti-MAG mAb (n=33 injured, n=21 sham) or control IgG (n=26 injured, n=22 sham) was infused intracerebroventricularly for 72 h. One group of these rats (n=14 sham, n=11 injured) was killed at 72 h post-injury for verification of drug diffusion and MAG immunohistochemistry. All other animals were evaluated up to 8 weeks post-injury using tests for neurologic motor, sensory and cognitive function. Hemispheric tissue loss was also evaluated at 8 weeks post-injury. At 72 h post-injury, increased immunoreactivity for MAG was seen in the ipsilateral cortex, thalamus and hippocampus of brain-injured animals, and anti-MAG mAb was detectable in the hippocampus, fimbria and ventricles. Brain-injured animals receiving anti-MAG mAb showed significantly improved recovery of sensorimotor function at 6 and 8 weeks (P<0.01) post-injury when compared with brain-injured IgG-treated animals. Additionally, at 8 weeks post-injury, the anti-MAG mAb-treated brain-injured animals demonstrated significantly improved cognitive function and reduced hemispheric tissue loss (P<0.05) when compared with their brain-injured controls. These results indicate that MAG may contribute to the pathophysiology of experimental TBI and treatment strategies that target MAG may be suitable for further evaluation.

Animals↗

PubMed1978

Correction of muscle imbalance in spasticity.

A summary is presented of observations made and results obtained during evaluation and preliminary treatment of twenty-one predominantly spastic cerebral palsied subjects, whose neuromuscular function was studied in each of four positions (supine, prone, kneeling and sitting on the floor) and in three dynamic situations (rising to standing, maintaining standing balance, and ambulating). A description is given of the procedures utilized to; (i) correct the imbalance of muscle tone imposing abnormal "resting" joint positions and limiting the range of their voluntary movements, and (ii) assist them in developing the sensorimotor function requisite for postural stability and voluntary motor control, involving exercises performed in each of the four positions and in transitions between them. Resistance exercises performed with the investigator and independent exercises both were included in the program. Case studies of a six-year-old spastic with "pre-athetoid" tendencies, an 11-year old spastic and a 32-year-old spastic are provided to illustrate typical initial evaluations, therapeutic activities subsequently utilized to improve neuromuscular function, and results thereby obtained.

Adult↗

PubMed2001

Number, origins, and chemical types of rat pallidostriatal projection neurons.

The dorsal globus pallidus (GP) receives major inputs from the dorsal neostriatum (Str), the subthalamic nucleus (STN) and the dorsal thalamus. The GP projects to multiple basal ganglia nuclei. One of the GP projection sites is the Str. The pallidostriatal projection has been considered minor. However, several recent studies have suggested that this projection is heavier than previously thought and that it might play a significant role in controlling the activity of the Str. To reveal more details of this projection, we examined the number of GP neurons that participated in the projection, their origins in the GP and their immunoreactivity for the calcium binding protein parvalbumin (PV), by using a combination of Fluoro-Gold (FG) retrograde labeling and immunohistochemical methods. Immunostaining for the calcium binding protein calbindin-28K (CaBP) was used to identify the CaBP-poor sensorimotor and CaBP-rich associative Str regions and the corresponding CaBP-poor middle, CaBP-rich border, and the caudomedial GP regions. The CaBP-poor dorsolateral Str region occupies a small portion of the Str, whereas the CaBP-poor middle GP region occupies a large portion of the GP. The immunostaining for neuron-specific nuclear protein (NeuN) was used to visualize neurons that were immunonegative for FG or PV. Cell counts revealed that the middle GP region contained a higher density of neurons and also a higher percentage of PV-positive neurons than the border and caudomedial regions of the GP. These observations suggested that the GP is involved more in sensorimotor function than associative function. Approximately 40% of neurons in the CaBP-poor middle GP region project to the CaBP-poor part of the dorsolateral Str. Approximately 30% of the neurons in both the CaBP-rich border and the caudomedial GP regions project to the CaBP-rich Str region. More than 40% of the pallidostriatal neurons in CaBP-poor middle GP region are PV-positive, whereas most of those in CaBP-rich GP regions are PV-negative. It was estimated from the cell count data that most of the PV-negative neurons in all three regions of the GP project to the Str. The results indicate that the sensorimotor and associative territories of the Str have reciprocal projections between corresponding territories of the GP. The involvement of a large number of GP neurons suggested that the pallidostriatal projection should be taken into account in the analysis of functional roles of the basal ganglia.

Animals↗

PubMed2001

Association between personal and environmental factors and the occurrence of handicap situations following a stroke.

BACKGROUND AND PURPOSE: Little is known about the potential role of environmental factors in the handicap creation process following a stroke. The objective of this study was to explore the presence of a relationship between environmental factors and the occurrence of handicap following a stroke, taking into consideration age and the level of impairments and disabilities. METHODS: This is a cross-sectional study where data were collected 6 months after discharge from an intensive functional rehabilitation unit. A convenience sample of 51 participants was recruited at the time of their admission to the rehabilitation unit for rehabilitation post-stroke. Perceived influence of environmental factors was measured using the Measure of the Quality of the Environment (MQE). Handicap situations were measured with the Assessment of Life Habits (LIFE-H). Impairments and disabilities comprised six domains (cognition, perception. depression, communication, sensorimotor function and comorbidity) assessed using a variety of measuring tools from which a composite score was derived. RESULTS: Fifty-one participants aged 40-97 years old took part in this study. Perceived obstacles in the environment, together with age and the level of impairments and disabilities, explained 58.9% of the variation in the LIFE-H (handicap level). Taken alone, the perceived obstacles (total score) explained 6.2%. The perceived facilitators (total score) in the environment were not found to be related to the presence of handicap situations. CONCLUSION: Increased level of impairments and disabilities. advanced age and perceived barriers in the physical and social environment contribute to the handicap creation process following a stroke.

Activities of Daily Living↗

PubMed2003

Ontogenetic trends in gnostic hand function in 3- to 12-yr-old children.

The intimate relation between the sensory and motor functions of the hands during object manipulation and exploratory touch, the well-known improvement in object handling and constructive performance in ontogenesis and the emergent laterality thereof, assume changes in morphognostic capabilities in children. In this study we tried to corroborate the hypothesis of Mesker that mature and lateralized finger-thumb opposition is preceded by a stage of two-sided manual form agnosia in preschool children, followed by acquisition of morphognosis of the fingers and, finally, the thumbs. This study examined the development of gnostic hand function in 290 children from 3 to 11 years of age who drew the outlines of a meaningless wooden object passively felt with each hand without visual control. Analysis showed a clear ontogenetic change across the two age groups of increasing morphognostic function: 48% of the 6-yr.-olds drew correctly what the fingers of both left and right hands had perceived (thumbs, 14%). Of the 11-yr.-olds 91% and 61% performed perfectly with the right and left hands, respectively. The fingers preceded the thumbs in reproduction by most children, and the correct reproduction by the left thumb precedes that of the right thumb. The ontogenesis of bimanual sensorimotor functioning is discussed in the light of cortical and callosal development.

Age Factors↗