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Forelimb use after focal cerebral ischemia in rats treated with an alpha 2-adrenoceptor antagonist.

Atipamezole, a selective alpha(2)-adrenoceptor antagonist, enhances recovery of sensorimotor function after focal cerebral ischemia in rats. The aim of the present study was to further characterize the effects of atipamezole treatment combined with enriched-environment housing in ischemic rats by evaluating spontaneous exploratory activity in the cylinder test. The right middle cerebral artery (MCA) of rats was occluded for 120 min using the intraluminal filament method. Atipamezole (1.0 mg/kg) or 0.9% NaCl was administered on postoperative days 2 through 11 and 15, 19, and 23. Spontaneous behavior of rats in a transparent cylinder was videotaped before, and 6 and 23 days after surgery 20 min after drug administration. Constant asymmetry in forelimb use was observed in the cylinder test on postoperative days 6 and 23. Ischemic rats used the impaired forelimbs (contralateral to lesion) during lateral exploration less than did sham-operated rats (P<.001). Ischemic rats also preferred to turn contralateral to the lesion (P<.05). Atipamezole increased the simultaneous, but not independent, use of the forelimbs during lateral exploration (P<.05). The data suggest that noradrenergic manipulation does not significantly enhance recovery in a test that does not depend on practice following focal cerebral ischemia.

Adrenergic alpha-2 Receptor Antagonists↗

An hypothesis about redundancy and reliability in the brains of higher species: analogies with genes, internal organs, and engineering systems.

The phenomena of behavioral resistance to massive brain damage and behavioral recovery from brain damage suggest there is redundancy in neural tissue. This paper uses basic concepts from probability theory and reliability engineering, as a first step toward more rigorously establishing the plausibility of the redundancy hypothesis. Exponential effects in the relevant formulas lead to results that are intuitively surprising. Thus, within a broad range of parametric assumptions related to lifespan and number of neurons or neural subsystems, it appears that the human brain may be at least twice as large as it would have to be for short-term survival. Simple reliability models suggest that redundancies are in parallel connections of smallest subsystems, such as individual neurons. Other implications of the basic formulas concern the relation between backed-up subsystem reliability and lifetime usage frequency for each subsystem, and the evolution of approximately equal allocation of lifetime reliability among components of a system. In addition, the paper briefly reviews more complex reliability engineering approaches. Redundancy as a reason for neural mass action is compared to other theoretical reasons for mass action in sensorimotor function and learning. Relationships of the present hypothesis to other theories of recovery from brain damage and to theories of regressive trophic phenomena in ontogeny are briefly discussed; it is suggested that as stages of ontogeny progress, both redundancy and flexibility in simpler behavioral functions are traded away for a larger, more differentiated repertoire of complex functions and memories.

Animals↗

Suck and spit, don't blow: orbital emphysema after decompression surgery.

PURPOSE: To describe the occurrence of vision-threatening orbital emphysema in patients awakening from orbital decompression surgery and to assess risk factors and preventive measures. DESIGN: Small noncomparative case series. PARTICIPANTS: Three patients undergoing bilateral orbital two-wall decompression experienced significant orbital emphysema associated with persistent coughing and Valsalva at the time of extubation. INTERVENTION: In two patients, symptoms resolved with simple observation, whereas one patient required sedation, topical anesthesia around the endotracheal tube, and needle decompression of trapped air. MAIN OUTCOME MEASURES: Visual acuity, pupils, visual fields, and sensorimotor examination. RESULTS: No patient experienced a permanent deficit of visual or sensorimotor function. CONCLUSIONS: Acute orbital emphysema can occur after orbital decompression surgery despite the large bony opening created. Violent coughing spells at the time of extubation are more common in patients with a history of heavy tobacco use and may be causative. Opening the periorbita may be another specific predisposing risk factor. Knowledge of this dangerous phenomenon, along with appropriate perioperative management, may prevent this complication from occurring.

Acute Disease↗

Early onset of NMDA receptor GluR epsilon 1 (NR2A) expression and its abundant postsynaptic localization in developing motoneurons of the mouse hypoglossal nucleus.

Oro-facial sensorimotor function conducted by the brainstem is vital to newborn mammals, and N-methyl-D-aspartate (NMDA) receptors play an important role in the regulation. Here we examined the expression of NMDA receptor subunits in the mouse hypoglossal nucleus from embryonic day 13 (E13) through postnatal day 21 (P21). Compared with other brainstem regions, early onset of GluRepsilon1 (NR2A) mRNA expression was conspicuous to the embryonic hypoglossal nucleus. The expression peaked at P1-P7, when other brainstem regions just started to express it. At P1, GluRepsilon1 subunit was localized to asymmetrical synapses on motoneuron dendrites, particularly, on the postsynaptic junction membrane. In developing motoneurons, expressions of GluRepsilon2 (NR2B), GluRepsilon4 (NR2D), and GluRzeta1 (NR1) mRNAs were accompanied. Until P21, however, all of these subunits were down-regulated with particular reduction for GluRepsilon2 and GluRepsilon4 mRNAs. Similar patterns of temporal expressions were observed in motoneurons of other brainstem motor nuclei. Taking that high levels of GluRepsilon1, GluRepsilon2, and GluRzeta1 subunits are also found in the adult hippocampus and cerebral cortex, it can be assumed that NMDA receptors in developing motoneurons are highly potent and potentially involved in structural and functional development of the brainstem motor system.

Animals↗

Opioid, cannabinoid and vanilloid receptor localization on porcine cultured myenteric neurons.

Opioids and cannabinoids have profound inhibitory actions on intestinal motility which are mediated in part by their cognate receptors in the enteric nervous system. In the present study, we examined the expression of immunoreactivity for delta- and kappa-opioid receptors, CB(1)-cannabinoid receptors and type 1 vanilloid receptors by immunocytochemistry and confocal laser scanning microscopy on ileal myenteric neurons, isolated from juvenile pigs, that were <70 microm diameter in either axis and maintained for 1-2 weeks in primary culture. Immunoreactivities for delta-opioid and cannabinoid receptors were present in neurons immunoreactive for the cholinergic marker, choline acetyltransferase. Some neurons with delta-opioid receptor-like immunoreactivity were also immunoreactive for kappa-opioid, cannabinoid or vanilloid receptors. These observations indicate that receptors for cannabinoids or vanilloids are co-localized in opioid receptor-expressing myenteric neurons which modulate intestinal sensorimotor function.

Animals↗

Nocturnal motor coordination deficits in neuronal nitric oxide synthase knock-out mice.

Nitric oxide is formed in the brain primarily by neurons containing neuronal nitric oxide synthase (nNOS), though some neurons may express endothelial NOS (eNOS), and inducible NOS (iNOS) only occurs in neurons following toxic stimuli. Mice with targeted disruption of nNOS (nNOS-) display distended stomachs with hypertrophied pyloric sphincters reflecting loss of nNOS in myenteric plexus neurons. nNOS- animals resist brain damage following middle cerebral artery occlusions consistent with evidence that excess release of nitric oxide mediates neurotoxicity in ischemic stroke. Neuronal NOS- mice have no grossly evident defects in locomotor activity, breeding long-term depression in the cerebellum, long-term potentiation in the hippocampus, and overall sensorimotor function. However, nNOS- animals display excessive, inappropriate sexual behavior and dramatic increases in aggression. Because the cerebellum possesses the greatest levels of nNOS neurons in the brain, it was surprising that presumed cerebellar functions such as balance and coordination were grossly normal in nNOS- mice. These previous studies were all conducted during the day (between 1400 and 1600, lights on at 0700). We now report striking, discrete abnormalities in balance and motor coordination in nNOS-mice reflected selectively at night.

Animals↗

Why move the eyes if we can move the head?

To see while moving is a very basic and integrative sensorimotor function in vertebrates. To maintain visual acuity, the oculomotor system provides efficient compensatory eye movements for head and visual field displacements. Other types of eye movement allow the selection of new visual targets and binocular vision and stereopsis. Motor and premotor neuronal circuits involved in the genesis and control of eye movements are briefly described. The peculiar properties and robust biomechanics of the oculomotor system have allowed it to survive almost unchanged through vertebrate evolution.

Animals↗

Principles of motility and sensation testing.

Motility of the gastrointestinal tract includes the phenomena of contractile activity, tone, compliance, flow, and transit. Sensitivity of the gastrointestinal tract is intimately related to motility. A range of techniques, both invasive and noninvasive, can be applied to evaluate enteric sensorimotor function in health and disease. This article reviews the physiologic principles underpinning these techniques. Altertions in both sensitivity and motility are believed to be important in the origin of symptoms in the functional gastrointestinal disorders. The evolution of studies investigating motility and sensitivity in these disorders, using the previously mentioned techniques, is also considered.

Digestive System↗

Involvement of 5-HT(2C) receptors in the anti-immobility effects of antidepressants in the forced swimming test in mice.

Several recent studies have demonstrated that 5-HT(1A), 5-HT(1B) and 5-HT(3) receptors were implicated in the mechanism of action of antidepressants in the mouse forced swimming test. Despite extensive evidence for a role of 5-HT(2C) receptors in depression, the precise role of these receptors in the effects of clinically established antidepressants was not directly investigated in the mouse forced swimming test. This work was aimed at exploring interactions between several doses of Ro 60-0175, a recently available, full and selective 5-HT(2C) agonist, and antidepressant drugs in the mouse forced swimming test. Spontaneous locomotor activity was measured as an index of intact sensorimotor functions and the dose-effect of Ro 60-0175 alone, as well as interactions with several antidepressants, such as tricyclic antidepressants (imipramine, desipramine and maprotiline) and selective serotonin reuptake inhibitors (paroxetine, citalopram, fluoxetine, fluvoxamine and sertraline), were studied in the mouse forced swimming test. There was no intrinsic antidepressant-like effect of Ro 60-0175, but an impairment in locomotor function was detected when using doses higher than 4 mg/kg in the mouse. There was a synergistic effect of low doses of Ro 60-0175 with sub-active doses of imipramine, paroxetine, citalopram and fluvoxamine; an antagonism between the highest dose of Ro 60-0175 and the active doses of paroxetine and fluoxetine was also detected. There is evidence that 5-HT(2C) receptors may be involved in the action of antidepressants which are able to boost the concentration of serotonin in the synapse, i.e. SSRIs and imipramine

Animals↗

Reliability of the Modified Ordinal Scales of Psychological Development: a cognitive assessment battery for severe dementia.

Two reliability studies were performed on a recently developed cognitive assessment battery for severe dementia. The method, the Modified Ordinal Scales of Psychological Development (M-OSPD), is based on the Piagetian developmental model of sensorimotor functions. Procedures have been adapted from this test battery, which was originally applied to infants and small children, for the assessment of remaining cognitive capacity in severe dementia. Two independent interrater reliability studies were conducted. In these studies, two different raters simultaneously evaluated patients with severe dementia. One interrater reliability study was performed in a nursing home setting (Study 1), and the other reliability study consisted of a sample of community-residing patients (Study 2). The Global Deterioration Scale and the Mini-Mental State Examination were used to assess dementia severity. Study 1 (N = 22) resulted in an intraclass correlation coefficient (ICC) of .99 (p < .01) for the M-OSPD total score. Study 2 (N = 19) resulted in an ICC of .96 (p < .01) for the M-OSPD total score. The M-OSPD proved to be a reliable instrument in these studies. This cognitive assessment measure can provide meaningful information regarding the cognitive abilities of late-stage dementia patients. Until recently, these late-stage dementia patients had been considered untestable in studies that utilized conventional psychometric and mental status evaluation measures.

Aged↗

Dopamine in the lateral caudate-putamen of the rat is essential for somatosensory orientation.

The present study examined the possible localization of somatosensory orientation in the caudate-putamen (CP) of the rat. In the first experiment, 6-hydroxydopamine (6-OHDA) was injected into either the anterodorsal (AD), anteroventral (AV), posterodorsal (PD), or posteroventral (PV) CP. Only rats with PV-CP 6-OHDA injections showed impaired orientation scores. However, these PV injections often caused widespread CP dopamine (DA) depletions, and no specific CP region appeared to be particularly associated with somatosensory orientation. In the second experiment, multiple injections of 6-OHDA were directed toward the medial or lateral halves of the CP to assess their relative contributions directly. DA depletions confined to the lateral (but not medial) CP resulted in orientation deficits; these deficits were greater than would be predicted from the volume of CP/DA loss. Furthermore, the magnitude of the DA fluorescence loss in the lateral CP was more highly correlated with the orientation impairment than was the medial CP fluorescence loss. Thus the lateral CP contributes to sensorimotor functions to a greater extent than does the medial CP, but the volume of CP/DA depletion also appears important.

Animals↗

Response-related deficits following unilateral lesions of the medial agranular cortex of the rat.

Rats with lesions of the medial agranular frontal cortex (AGm) were tested for sensorimotor function. Spatial response bias and reaction time to lateralized visual targets were recorded in an automated test of visual reaction time. The same rats were also tested for somatosensory capacity and on a skilled reaching task. In all tasks, there was an ipsilateral response bias but no evidence of sensory neglect. In the visual reaction time task, initiation time was lengthened bilaterally. These deficits may parallel the effects on motor function after unilateral frontal cortical lesioning in primates. The results support the hypothesis that rat AGm contains a homologue of primate secondary motor cortex.

Afferent Pathways↗

Mutations that prevent associative learning in C. elegans.

The nematode Caenorhabditis elegans offers a promising system for the reductionist study of learning and memory. In this article, classical conditioning in C. elegans is demonstrated with a variety of associative learning assays. These assays allowed for the isolation and behavioral characterization of 2 mutant C. elegans lines impaired in associative learning. Both lines show no short-term or long-term associative conditioning; however, they appear relatively normal in tests of nonassociative learning and sensorimotor function. In combination with the well-described genetics and neuroanatomy of C. elegans, the isolation of mutants selectively, yet completely, blocked in associative learning provides the basis for an effective characterization of the cellular and molecular aspects of associative learning.

Animals↗

Assessment of sensorimotor neglect after occlusion of the middle cerebral artery in the rat.

Evaluating the efficacy of neuroprotective drugs in rat models of focal cerebral ischemia has involved histological and behavioral batteries to examine treatment outcome. However, the behavioral tests used to date provide little insight into the nature of the neurological impairments. To provide an analysis of a possible "neglect" syndrome after occlusion of the middle cerebral artery, M. I. Posner's (1980) visual attentional paradigm was adapted for use in the rat. A paw-reaching task and a test of somatosensory "neglect" also were used to assess forelimb sensorimotor function. The lesion group displayed unilateral deficits; however, there was no evidence of attentional dysfunction. Results are consistent with the conclusion that the behavioral deficits identified arise from a somatosensory deficit rather than hemineglect due to dysfunctional spatial attention.

Animals↗

Reversible inactivation of the medial septum or nucleus basalis impairs working memory in rats: a dissociation of memory and performance.

Lidocaine-induced inactivation of the medial septum immediately after training or prior to testing in a delay radial-arm maze task produced deficits in spatial working memory that reflected impaired acquisition of the task. Injection of lidocaine into the nucleus basalis magnocellularis produced a profile of behavioral changes that indicated that temporary inactivation of this structure impaired the behavioral expression of information already stored in working memory. This appears to reflect an impairment in processes that are required for performance (i.e., attention, motivation, sensorimotor function) of the task but not for retrieval of stored information. Site-specific inactivation of the basal forebrain should help to reveal the involvement of its component structures in different aspects of cognitive function.

Analysis of Variance↗

Effect of dopamine-depleting brain lesions on suckling and weaning in rats.

Rats given large dopamine-depleting brain lesions as adults exhibit severe impairments in ingestive behavior and sensorimotor function. In contrast to these well-known effects, virtually complete destruction of central dopaminergic neurons produced no such dysfunctions when it occurred in neonates. Indeed, rats continued to suckle and grow, albeit somewhat more slowly, and they could be weaned readily when they were 27 days old. Although most brain-damaged animals did not survive weaning when they were 18 days old, whereas controls exhibited no difficulty, this failure appears to be the consequence of their reduced body weight and related inability to maintain body temperature in a relatively cool environment (22 degrees C). Such premature weaning occurred more successfully when growth was stimulated by rearing brain-damaged pups in small litters or when ambient temperatures were raised to 31 degrees C so as to minimize heat loss. These results demonstrate that the effects of near-total dopamine-depleting brain lesions are considerably less severe when they occur in infants than when they occur in adults, and, consequently, they reveal a capacity for neural plasticity during development that is no longer present at maturity.

Animals↗

Bilateral cutaneous stimulation of the somatosensory system in hemidecorticate rats.

An enduring somatosensory consequence of extensive neocortex injury in people is "simultaneous extinction," which is an interhemispheric perceptual interaction that is operationally distinguishable from neglect. A cutaneous stimulus presented on the contralateral side of the body is readily detected when presented singly but is actively masked during bilateral stimulation. In hemidecorticate rats, small adhesive stimuli were attached to the radial surface of each forelimb simultaneously, and the latencies to contact and to remove each stimulus were recorded. Neglect of the contralateral stimulus lasted 2-3 days. Thereafter the ipsilateral stimulus was removed first, followed immediately by the contralateral stimulus. This ipsilateral sensorimotor bias lasted several months. Further analysis with unremovable tactile stimuli provided evidence for true extinction. For a limited period (during the first 2 postoperative weeks), the contralateral stimulus did not appear to be detected in the presence of the ipsilateral stimulus. Rather than switching back and forth between the two stimuli, the animals ignored the stimulus on the contralateral limb and persisted in their attempts to remove the ipsilateral stimulus. A key feature of the "extinction" was its complete reversibility. Simply by adjusting the sensory fields occupied by the contralateral (C) and ipsilateral (I) stimuli (specifically, by increasing the C/I ratio), the sensorimotor bias was totally shifted to contralateral. During recovery, the size of the C/I ratio necessary to reverse sensorimotor asymmetry gradually decreased. Asymmetrical sensorimotor behavior and amphetamine-induced circling were examined in three additional groups of hemidecorticate rats, which were given their initial behavioral tests at 2, 12, or 52 postoperative weeks. This experiment confirmed the above findings and controlled for practice. Over the course of a year, apparently complete recovery occurred; however, there were residual effects. At each period, previously recovered symptoms were reinstated simply by turning on the room lights and opening the home cage slightly. These data underscore the importance of detailed behavioral analysis and the value of the rat as a model in studies of recovery of sensorimotor function.

Afferent Pathways↗

Roles of anoxia and noise-induced hearing loss in the postictal refractory period for audiogenic seizures in mice.

The present series of experiments demonstrated a postictal refractory period for audiogenic seizures in DBA/2J mice, which was not related to hearing loss but apparently was related to anoxia. Unlike many previous studies, Experiment 1 controlled for the effects of noise exposure upon hearing sensitivity and demonstrated reduced susceptibility to subsequent audiogenic seizures for at least 1 hr after initial clonic-tonic convulsions. The postictal refractory period was shown to result from the occurrence of seizures per se, not from noise exposure alone. Experiment 2 demonstrated deficiencies of sensorimotor functions that accompanied reduced postictal seizure susceptibility. The two phenomena had similar time courses of recovery, which suggested a common mechanism, probably anoxia, associated with the initial convulsions. In support of this view, Experiment 3 showed that recovery from both phenomena was expedited by allowing subjects to breathe increased O2. The role of anoxia in fatal convulsions was suggested by the finding that subjects experiencing clonic-tonic convulsions in a high-O2 environment survived without exception. In contrast, seizures of air-breathing controls were almost always fatal. Taken together, the data indicate that the postictal reduced susceptibility to audiogenic seizures was closely related to metabolic depletion (in particular, anoxia). The pattern of recovery of susceptibility further suggests that the effects of anoxia impair the spread of seizure activity through the central nervous system, although the initiation of seizures is also affected for a short time.

Anesthesia, Inhalation↗