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Query: UMLS:C0599766 (functional recovery)
 13,441 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We used a kinematic analysis for assessing locomotor impairments and evaluating the time course of recovery after focal injury to the forepaw area of the primary somatosensory cortex (SI) in rats. The animals were trained to traverse a beam that was rotated at various speeds. Changes in orientation of the body and independent movement of the anterior and posterior parts of the body were reconstructed using a 3D motion analysis. In addition, we used electrophysiological cortical mapping to search for neurophysiological changes within the spared cortical zones surrounding the lesion. Neuronal recordings were performed in the same animals prior to and 3 weeks after the lesion induction. Our findings show that a focal lesion that destroyed about 60% of the forepaw representational zone was sufficient to cause conspicuous impairments in the rats' ability to produce adequate motor adjustments to compensate for the lateral shift of the beam and to avoid falling. The main deficits were reflected in a lack of appropriate coordination between the anterior and posterior parts of the body and an inability to maintain a regular gait during locomotion. Skilled locomotion was fully recovered within a 2-3 week period. Functional recovery cannot be ascribed to a restitution of the lost sensory representations. A permanent decrease of forepaw representation was recorded despite the re-emergence of restricted representational sectors in the peri-lesion zone. We suggest that alterations may have occurred in other cortical and subcortical areas interconnected with the injured area. It is also conceivable that the functional recovery involved an increased reliance on all the available sources of sensorimotor regulation as well as the use of behavioral strategies.
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PMID:Deficits and recovery of body stabilization during acrobatic locomotion after focal lesion to the somatosensory cortex: a kinematic analysis combined with cortical mapping. 1526 56

Neuronal function and morphology are affected by the environment and the behavioral experience. Here we report on the effects of differential training protocols on the development and the functional recovery mediated by intrastriatal striatal grafts. Rats were trained exclusively on the left or the right paw to perform on the skilled staircase task before being lesioned unilaterally in the dorsal striatum with quinolinic acid. E15 whole ganglionic eminence suspension grafts were implanted into the lesioned striatum. Subsequent testing probed unilateral performance of the affected contralateral paw, as well as bilateral performance. The grafted animals were initially as impaired as the lesioned, but partially recovered their performance with additional training. Grafted animals with appropriate previous experience initially performed better on the staircase test, but the advantage was transient. Furthermore, the grafted animals performed better with their affected paw under forced choice than under conditions when both paws were simultaneously probed. Improvements of the grafted animals were also observed on tests of forelimb akinesia and asymmetry. Morphological data suggest that the training conditions influenced the development specifically of striatal-like, but not of non-striatal like, neurones within the grafts. The grafts were smaller containing less striatal-like neurones in animals that were trained on the contralateral side prior to lesioning and grafting. The results support the hypothesis that unilateral training sensitizes the striatum that subserves the motor learning, leading to exacerbated excitotoxic lesions and to an environment less conducive for graft development.
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PMID:Training specificity, graft development and graft-mediated functional recovery in a rodent model of Huntington's disease. 1583 16

A reorganization of cortical representations is postulated as the basis for functional recovery following many types of nervous system injury. Neuronal mechanisms underlying this form of cortical plasticity are poorly understood. The present study investigated the hypothesis that the basal forebrain cholinergic system plays an essential role in enabling the cortical reorganization required for functional recovery following brain injury. The results demonstrate that functional recovery following cortical injury requires basal forebrain cholinergic mechanisms and suggest that the basis for this recovery is the cholinergic-dependent reorganization of motor representations. These findings raise the intriguing possibility that deficits in cholinergic function may limit functional outcomes following nervous system injury.
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PMID:The basal forebrain cholinergic system is essential for cortical plasticity and functional recovery following brain injury. 1584 97

Neuronal death due to ischemic stroke results in permanent deficits in sensory, language, and motor functions. The growth-restrictive environment of the adult central nervous system (CNS) is an obstacle to functional recovery after stroke and other CNS injuries. In this regard, Nogo-A is a potent neurite growth-inhibitory protein known to restrict neuronal plasticity in adults. Previously, we have found that treatment with monoclonal antibody (mAb) IN-1 to neutralize Nogo-A immediately after stroke enhanced motor cortico-efferent plasticity and recovery of skilled forelimb function in rats. However, immediate treatment for stroke is often not clinically feasible. Thus, the present study was undertaken to determine whether cortico-efferent plasticity and functional recovery would occur if treatment with mAb IN-1 was delayed 1 week after stroke. Adult rats were trained on a forelimb-reaching task, and the middle cerebral artery was occluded to induce focal cerebral ischemia to the forelimb sensorimotor cortex. After 1 week, animals received mAb IN-1 treatment, control antibody, or no treatment, and were tested for 9 more weeks. To assess cortico-efferent plasticity, the sensorimotor cortex opposite the stroke lesion was injected with an anterograde neuroanatomical tracer. Behavioral analysis demonstrated a recovery of skilled forelimb function, and anatomical studies revealed neuroplasticity at the level of the red nucleus in animals treated with mAb IN-1, thus demonstrating the efficacy of this treatment even if administered 1 week after stroke.
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PMID:Delayed treatment with monoclonal antibody IN-1 1 week after stroke results in recovery of function and corticorubral plasticity in adult rats. 1588 44

Neuronal circuits in the brain are shaped by experience during 'critical periods' in early postnatal life. In the primary visual cortex, this activity-dependent development is triggered by the functional maturation of local inhibitory connections and driven by a specific, late-developing subset of interneurons. Ultimately, the structural consolidation of competing sensory inputs is mediated by a proteolytic reorganization of the extracellular matrix that occurs only during the critical period. The reactivation of this process, and subsequent recovery of function in conditions such as amblyopia, can now be studied with realistic circuit models that might generalize across systems.
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PMID:Critical period plasticity in local cortical circuits. 1626 Nov 81

This study was designed to assess a new composite implant to induce regeneration of injured spinal cord in paraplegic rats following complete cord transection. Neuronal xenogeneic cells from biopsies of adult nasal olfactory mucosa (NOM) of human origin, or spinal cords of human embryos, were cultured in two consecutive stages: stationary cultures in a viscous semi-solid gel (NVR-N-Gel) and in suspension on positively charged microcarriers (MCs). A tissue-engineered tubular scaffold, containing bundles of parallel nanofibers, was developed. Both the tube and the nanofibers were made of a biodegradable dextran sulphate-gelatin co-precipitate. The suturable scaffold anchored the implant at the site of injury and provided guidance for the regenerating axons. Implants of adult human NOM cells were implanted into eight rats, from which a 4 mm segment of the spinal cord had been completely removed. Another four rats whose spinal cords had also been transected were implanted with a composite implant of cultured human embryonic spinal cord cells. Eight other cord-transected rats served as a control group. Physiological and behavioral analysis, performed 3 months after implantation, revealed partial recovery of function in one or two limbs in three out of eight animals of the NOM implanted group and in all the four rats that were implanted with cultured human embryonic spinal cord cells. Animals of the control group remained completely paralyzed and did not show transmission of stimuli to the brain. The utilization of an innovative composite implant to bridge a gap resulting from the transection and removal of a 4 mm spinal cord segment shows promise, suggesting the feasibility of this approach for partial reconstruction of spinal cord lesions. Such an implant may serve as a vital bridging station in acute and chronic cases of paraplegia.
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PMID:Development of a tissue-engineered composite implant for treating traumatic paraplegia in rats. 1629 87

CNS axons rarely regenerate spontaneously back to original targets following spinal cord injury (SCI). Neuronal expression of the serine protease tissue-type plasminogen activator (tPA) enhances axon growth in vitro and following PNS injury. Here we test the hypothesis that neuronal overexpression of tPA in adult transgenic mice promotes CNS axon regeneration and functional recovery following SCI. Adult wild-type and transgenic mouse spinal cords were subjected to dorsal hemisection at the level of the T10/T11 vertebrae. PCR confirmed incorporation of the transgene. Immunolabeling revealed overexpression of tPA in transgenic mice in neurons, including large-diameter neurons in lumbar dorsal root ganglia that contribute axons to the dorsal columns. Immunolabeling also revealed the presence of tPA protein within axons juxtaposing the injury site in transgenics but not wild types. In situ zymography revealed abundant enzymatic activity of tPA in gray matter of thoracic spinal cords of transgenics but not wild types. Rotorod locomotor testing revealed no differences between groups in locomotor function up to 21 days postinjury. Transganglionic tracer was injected into the crushed right sciatic nerve 28 days postinjury, and mice were killed 3 days later. There was no evidence for regrowth of ascending dorsal column sensory axons through or beyond the injury site. In conclusion, despite neuronal overexpression of tPA in injured neurons of transgenics, neither locomotor recovery nor regeneration of ascending sensory axons was observed following thoracic dorsal hemisection.
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PMID:Neuronal overexpression of tissue-type plasminogen activator does not enhance sensory axon regeneration or locomotor recovery following dorsal hemisection of adult mouse thoracic spinal cord. 1691 39

We examined the effects of age on stroke progression and outcome in order to explore the association between blood-brain barrier (BBB) disruption, neuronal damage, and functional recovery. Using middle cerebral artery occlusion (MCAO), young (3 months) and aged (18 months) rats were assessed for BBB disruption at 20min post-MCAO, and 24h post-MCAO with tissue plasminogen activator induced reperfusion at 120min. Results showed that BBB disruptions in aged rats occurred early and increased nearly two-fold at both the 20min and 24h time points when compared to young animals. Neuronal damage in aged rats was increased two-fold as compared to young rats at 24h, while no neuronal damage was observed at 20min. Young and aged rats exhibited neurological deficits when compared to sham-controls out to 14 days following MCAO and reperfusion; however, aged rats exhibited more severe onset of deficits and prolonged recovery. Results indicate that aged rats suffer larger infarctions, reduced functional recovery and increased BBB disruption preceding observable neuronal injury.
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PMID:Early disruptions of the blood-brain barrier may contribute to exacerbated neuronal damage and prolonged functional recovery following stroke in aged rats. 1724 2

The toxicity of released glutamate contributes substantially to secondary cell death following spinal cord injury (SCI). In this work, the extent and time courses of glutamate-induced losses of neurons and oligodendrocytes are established. Glutamate was administered into the spinal cords of anesthetized rats at approximately the concentration and duration of its release following SCI. Cells in normal tissue, in tissue exposed to artificial cerebrospinal fluid and in tissue exposed to glutamate were counted on a confocal system in control animals and from 6 h to 28 days after treatment to assess cell losses. Oligodendrocytes were identified by staining with antibody CC-1 and neurons by immunostaining for Neuronal Nuclei (NeuN) or Neurofilament H. The density of oligodendrocytes declined precipitously in the first 6 h after exposure to glutamate, and then relatively little from 24 h to 28 days post-exposure. Similarly, neuron densities first declined rapidly, but at a decreasing rate, from 0 h to 72 h post-glutamate exposure and did not change significantly from 72 h to 28 days thereafter. The nuclei of many cells strongly and specifically stained for activated caspase-3, an indicator of apoptosis, in response to exposure to glutamate. Caspase-3 was localized to the nucleus and may participate in apoptotic cell death. However, persistence of caspase-3 staining for at least a week after exposure to glutamate during little to no loss of oligodendrocytes and neurons demonstrates that elevation of caspase-3 does not necessarily lead to rapid cell death. Beyond about 48 h after exposure to glutamate, locomotor function began to recover while cell numbers stabilized or declined slowly, demonstrating that functional recovery in the experiments presented involves processes other than replacement of oligodendrocytes and/or neurons.
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PMID:Glutamate-induced losses of oligodendrocytes and neurons and activation of caspase-3 in the rat spinal cord. 1842 97

In a model of glial-specific chemical anoxia, we have examined how astrocytes influence both synaptic transmission and the viability of hippocampal pyramidal neurons. This relationship was assessed using electrophysiological, pharmacological, and biochemical techniques in rat slices and cell cultures, and oxidative metabolism was selectively impaired in glial cells by exposure to the mitochondrial gliotoxin, fluoroacetate. We found that synaptic transmission was blocked shortly after inducing glial metabolic stress and peri-infarct-like spreading depression (SD) waves developed within 1 to 2 h of treatment. Neuronal electrogenesis was not affected until SD waves developed, thereafter decaying irreversibly. The blockage of synaptic transmission was totally reversed by A(1) adenosine receptor antagonists, unlike the development of SD waves, which appeared earlier under these conditions. Such blockage led to a marked reduction in the electrical viability of pyramidal neurons 1 h after gliotoxin treatment. Cell culture experiments confirmed that astrocytes indeed release adenosine. We interpret this early glial response as a novel safety mechanism that allocates metabolic resources to vital processes when the glia itself sense an energy shortage, thereby delaying or preventing entry into massive lethal ischemic-like depolarization. The implication of these results on the functional recovery of the penumbra regions after ischemic insults is discussed.
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PMID:Metabolic challenge to glia activates an adenosine-mediated safety mechanism that promotes neuronal survival by delaying the onset of spreading depression waves. 1861 16


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