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

Traumatic injury of the central nervous system results in formation of a collagenous basement membrane-rich fibrous scar in the lesion centre. Due to accumulation of numerous axon-growth inhibitory molecules the lesion scar is considered a major impediment for axon regeneration. Following transection of the dorsal corticospinal tract (CST) at thoracic level 8 in adult rats, transient suppression of collagenous scarring in the lesion zone by local application of a potent iron chelator and cyclic adenosine monophosphate resulted in the delay of fibrous scarring. Treated animals displayed long-distance growth of CST axons through the lesion area extending for up to 1.5-2 cm into the distal cord. In addition, the treatment showed a strong neuroprotective effect, rescuing cortical motoneurons projecting into the CST that normally die (30%) after thoracic axotomy. Further, anterogradely traced CST axons regenerated through both grey and white matter and developed terminal arborizations in grey matter regions. In contrast to controls, injured animals receiving treatment showed significant functional recovery in the open field, in the horizontal ladder and in CatWalk locomotor tasks. We conclude that the fibrous lesion scar plays a pivotal role as a growth barrier for regenerating axons in adult spinal cord and that a delay in fibrotic scarring by local inhibition of collagen biosynthesis and basement membrane deposition is a promising and unique therapeutic strategy for treating human spinal trauma.
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PMID:Suppression of fibrous scarring in spinal cord injury of rat promotes long-distance regeneration of corticospinal tract axons, rescue of primary motoneurons in somatosensory cortex and significant functional recovery. 1636 71

The mechanisms underlying functional recovery after stroke are poorly understood. Brain-adaptive responses to the hypoxic stress elicited by ischemia could contribute to these mechanisms. Indeed, hypoxia-inducible factor-1 (HIF-1), one of the main transcriptional factors regulated by oxygen level, increases the expression of several beneficial genes such as erythropoietin, glucose transporter-1 and vascular endothelial growth factor. In order to strengthen the expression of these hypoxia-inducible factors, we administered deferoxamine, an iron chelator known to stabilize HIF-1alpha protein expression, and examined its effects on the functional deficits induced by ischemia. Anesthetized Sprague-Dawley rats were subjected to 60 min of intraluminal occlusion of the middle cerebral artery. Chronic deferoxamine treatment (300 mg/kg, s.c.), or its vehicle, started 24 h after ischemia and was continued bi-weekly until the animals were killed. Sensorimotor deficits were periodically assessed over 2 months, and at this end point, the lesion volume was determined by histology. Treatment with deferoxamine significantly decreased the size of brain damage (-28%) after ischemia and improved behavioral recovery. Indeed, neurological score and sensorimotor performances in the adhesive removal test recovered earlier in the deferoxamine-treated animals. Moreover, the long-lasting skilled forepaw reaching deficits were attenuated by deferoxamine. Although an antioxidant effect of deferoxamine cannot be excluded, the hypothesis that its beneficial effects could be mediated by an increase in HIF-1 target genes merits further investigations. Our data suggest that delayed administration of deferoxamine could represent an interesting therapeutical approach to treat focal cerebral ischemia.
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PMID:Delayed administration of deferoxamine reduces brain damage and promotes functional recovery after transient focal cerebral ischemia in the rat. 1662 32

Cerebral hemorrhage leads to local production of free iron, radicals, cytokines, etc. To investigate whether a decrease of iron-mediated radical production influences functional recovery after intracerebral hemorrhage (ICH), a modified ICH rat model with a small hemorrhage near the internal capsule (IC) accompanied with relatively severe motor dysfunction was first developed. Then clioquinol (CQ), an iron chelator that reduces hydroxyl radical production, was orally administrated. Injection of different doses of Type IV collagenase (1.4 mul 1-200 U/ml) into the left striatum near the IC in Wistar rats showed that injection of 7.5 U/ml collagenase resulted in a small hemorrhoidal lesion near the IC with relatively severe motor dysfunction (IC model). Retrograde labeling of neurons in the sensory-motor cortex and axons in the corticospinal tract using Fluoro-gold (FG) injection into the spinal cord (C3-C4) showed that few labeled neurons in the sensory-motor cortex were detected in the IC model, FG-labeled axons disappeared, and FG-including ED-1-positive cells appeared within 24 hr in the IC. Assessments of behavior and histologic analysis after oral administration of CQ in the IC model indicated that oral administration of CQ prevented a decrease of FG-labeled neurons, and resulted in better motor-function recovery. CQ inhibited hydrogen peroxide-induced cell toxicity in oligodendrocytes in vitro, but not in neurons. Our data suggests that CQ ameliorated motor dysfunction after a small hemorrhage near the IC by a mechanism that is related to reduction of chain-reactive hydroxyl radical production in oligodendrocytes.
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PMID:Oral administration of metal chelator ameliorates motor dysfunction after a small hemorrhage near the internal capsule in rat. 1706 Dec 55

Cellular magnetic resonance (MR) imaging is a rapidly growing field that aims to visualize and track cells in living organisms. Superparamagnetic iron oxide (SPIO) nanoparticles offer a sufficient signal for T2 weighted MR images. We followed the fate of embryonic stem cells (ESCs) and bone marrow mesenchymal stem cells (MSCs) labeled with iron oxide nanoparticles (Endorem) and human CD34+ cells labeled with magnetic MicroBeads (Miltenyi) in rats with a cortical or spinal cord lesion, models of stroke and spinal cord injury (SCI), respectively. Cells were either grafted intracerebrally, contralaterally to a cortical photochemical lesion, or injected intravenously. During the first post-transplantation week, grafted MSCs or ESCs migrated to the lesion site in the cortex as well as in the spinal cord and were visible in the lesion on MR images as a hypointensive signal, persisting for more than 30 days. In rats with an SCI, we found an increase in functional recovery after the implantation of MSCs or a freshly prepared mononuclear fraction of bone marrow cells (BMCs) or after an injection of granulocyte colony stimulating factor (G-CSF). Morphometric measurements in the center of the lesions showed an increase in white matter volume in cell-treated animals. Prussian blue staining confirmed a large number of iron-positive cells, and the lesions were considerably smaller than in control animals. Additionally, we implanted hydrogels based on poly-hydroxypropylmethacrylamide (HPMA) seeded with nanoparticle-labeled MSCs into hemisected rat spinal cords. Hydrogels seeded with MSCs were visible on MR images as hypointense areas, and subsequent Prussian blue histological staining confirmed positively stained cells within the hydrogels. To obtain better results with cell labeling, new polycation-bound iron oxide superparamagnetic nanoparticles (PC-SPIO) were developed. In comparison with Endorem, PC-SPIO demonstrated a more efficient intracellular uptake into MSCs, with no decrease in cell viability. Our studies demonstrate that magnetic resonance imaging (MRI) of grafted adult as well as ESCs labeled with iron oxide nanoparticles is a useful method for evaluating cellular migration toward a lesion site.
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PMID:In vivo tracking of stem cells in brain and spinal cord injury. 1761 91

The Rose Bengal model in rats is widely used to study brain plasticity, functional recovery and restorative therapies. The present study evaluated temporal profiles of hemorrhage and edema by magnetic resonance imaging (MRI) in rats in relation to sensorimotor impairment after photochemically induced cortical infarct. Adult, male Wistar rats were injected with Rose Bengal dye followed by illumination to produce a lesion over the sensorimotor cortex. Brain damage including infarct volume, edema, and bleeding was determined from postoperative days 1 to 10 by using MRI. Prussian blue staining was used to confirm hemorrhage in perfused brain sections. Functional outcome was assessed by limb-placing test during the follow-up. A consistent cortical lesion was detected in T(2) weighted MRI 24h after cortical photothrombosis without any signs of blood in T(2)(*) weighted images. However, from postoperative days 3 to 8, hemorrhage was indicated by almost complete signal void in T(2)(*) weighted gradient echo images and confirmed by Perls' Prussian blue staining on postoperative day 10 for presence of iron in corresponding lesion areas. The subacute appearance of hemorrhage on postoperative days 3-8 and resolution of edema coincides with improved performance in the limb-placing test. The results suggest that bleeding around cortical infarct is part of the wound healing process and may not impair functional outcome.
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PMID:Subacute hemorrhage and resolution of edema in Rose Bengal stroke model in rats coincides with improved sensorimotor functions. 1795 10

The Authors, after having defined the phenomenon and the biological characteristics of natural magnets, evaluate their ability in accelerating the formation of bone callus in hand and wrist fractures compared to treatment with immobilization in a plaster cast. Forty patients (4 females and 37 males) between 20 and 86 years of age were treated. A small natural magnet was inserted in each of the plaster casts (diameter: 2cm, height: 0.5cm) made of 4 blocks in Neodymium-Iron-Boron, capable of generating 4 magnetic poles (2 positive and 2 negative) of diagonal alternate polarity that produced a symmetric, quadruple static magnetic field. The created magnetic flow was wavelike, concentrated in one direction, and developed a force up to 12,500 gauss. From this study it has emerged that inserting a quadruple magnet in a plaster cast in hand and wrist fractures results in the formation of bone callus in an average time that is 35% inferior to the "standard" time. Accelerating the healing of the fracture is important since it reduces immobilization time for the joints involved, avoiding subsequent weakness and stiffness and allowing the patient to begin rehabilitative physiotherapy sooner, which permits a faster functional recovery.
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PMID:Treatment of wrist and hand fractures with natural magnets: preliminary report. 1833 79

CNS injury-induced hemorrhage and tissue damage leads to excess iron, which can cause secondary degeneration. The mechanisms that handle this excess iron are not fully understood. We report that spinal cord contusion injury (SCI) in mice induces an "iron homeostatic response" that partially limits iron-catalyzed oxidative damage. We show that ceruloplasmin (Cp), a ferroxidase that oxidizes toxic ferrous iron, is important for this process. SCI in Cp-deficient mice demonstrates that Cp detoxifies and mobilizes iron and reduces secondary tissue degeneration and functional loss. Our results provide new insights into how astrocytes and macrophages handle iron after SCI. Importantly, we show that iron chelator treatment has a delayed effect in improving locomotor recovery between 3 and 6 weeks after SCI. These data reveal important aspects of the molecular control of CNS iron homeostasis after SCI and suggest that iron chelator therapy may improve functional recovery after CNS trauma and hemorrhagic stroke.
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PMID:Ceruloplasmin protects injured spinal cord from iron-mediated oxidative damage. 1903 66

Noninvasive cellular imaging allows the real-time tracking of grafted cells as well as the monitoring of their migration. Several techniques for in vivo cellular imaging are available that permit the characterization of transplanted cells in a living organism, including magnetic resonance imaging (MRI), bioluminescence, positron emission tomography, and multiple photon microscopy. All of these methods, based on different principles, provide distinctive, usually complementary information. In this review, we will focus on cell tracking using MRI, since MRI is noninvasive, clinically transferable, and displays good resolution, ranging from 50microm in animal experiments up to 300microm using whole body clinical scanners. In addition to information about grafted cells, MRI provides information about the surrounding tissue (i.e., lesion size, edema, inflammation), which may negatively affect graft survival or the functional recovery of the tissue. Transplanted cells are labeled with MR contrast agents in vitro prior to transplantation in order to visualize them in the host tissue. The chapter will focus on the use of superparamagnetic iron oxide nanoparticles (SPIO), because they have strong effects on T2 relaxation yet do not affect cell viability, and will provide an overview of different modifications of SPIO and their use in MR tracking in living organisms.
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PMID:MR tracking of stem cells in living recipients. 1937 5

Stem cell therapy in the nervous system aims to replace the lost neurons and provide functional recovery. However, it is imperative that we understand the in vivo behaviour of these cells post-implantation. We report visualisation of iron oxide labelled bone marrow-derived stem cells (BMSCs) implanted into the striatum of hemi-parkinsonian rats by magnetic resonance imaging (MRI). Functional efficacy of the donor cells was monitored in vivo using the positron emission tomography (PET) radioligand [11C]raclopride. The cells were visible for 28 days by in vivo MRI. BMSCs provided functional recovery demonstrated by a decreased binding of [11C]raclopride. Although, histology confirmed the persistence of donor cells, no tyrosine hydroxylase positive cells were present. This suggests that BMSCs may have a limited paracrine effect and influence functional recovery. We demonstrate, using multimodal imaging, that we can not only track BMSCs but also establish their effects in a pre-clinical model of Parkinson's disease.
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PMID:In vivo multimodal imaging of stem cell transplantation in a rodent model of Parkinson's disease. 1955 25

Deferoxamine (DFO) was granted orphan drug status for the treatment of traumatic spinal cord injury but its neuroprotective mechanism is not well understood. We therefore investigated the mode of action of DFO in serum-starved and/or iron-stressed cultures of rat dorsal root ganglion (DRG) cells. We probed for redox signaling by determining hemeoxygenase-1 activity and by measuring expression of intracellular iron metabolism-related proteins under pro-oxidative conditions. We also employed DNA microarrays to better understand the genomic response of DRG cultures to treatment with DFO thereby enabling the generation of hypotheses. Essentially, DFO treatment resulted in outgrowth of neurofilament 200-positive neurites and induction of synapse formation as determined by immunoblotting, transmission electron microscopy and immunofluorescence confocal microscopy. Furthermore, DFO treatment of DRG cell cultures activated neuroprotective and antioxidative programs such as matrix metallopeptidase 2 and apolipoprotein D to promote neurite regeneration. Indeed, DFO reduced markedly reactive oxygen species formation, increased the expression of hemeoxygenase-1 and improved iron management through regulation of transferrin receptor and ferritin. We propose DFO treatment of DRG cell cultures to completely abolish the oxidative effect of ferrous iron (Fe(2+)). Taken collectively, DFO reduced oxidative stress and induced synthesis of neuroprotective and antioxidative molecules to foster nerve repair and functional recovery. Our findings help to better understand the therapeutic benefit of DFO in the treatment of spinal cord injury.
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PMID:Deferoxamine-induced neurite outgrowth and synapse formation in postnatal rat dorsal root ganglion (DRG) cell cultures. 1958 Oct 22


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