Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0599766 (functional recovery)
 13,441 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cDNA encoding a P450 monooxygenase was amplified from reverse transcribed rat heart and liver total RNA by polymerase chain reaction using primers based on the 5'- and 3'-end sequences of two rat pseudogenes, CYP2J3P1 and CYP2J3P2. Sequence analysis revealed that this 1,778-base pair cDNA contained an open reading frame and encoded a new 502 amino acid protein designated CYP2J3. Based on the deduced amino acid sequence, CYP2J3 was approximately 70% homologous to both human CYP2J2 and rabbit CYP2J1. Recombinant CYP2J3 protein was co-expressed with NADPH-cytochrome P450 oxidoreductase in Sf9 insect cells using a baculovirus expression system. Microsomal fractions of CYP2J3/NADPH-cytochrome P450 oxidoreductase-transfected cells metabolized arachidonic acid to 14,15-, 11,12-, and 8, 9-epoxyeicosatrienoic acids and 19-hydroxyeicosatetraenoic acid as the principal reaction products (catalytic turnover, 0.2 nmol of product/nmol of cytochrome P450/min at 37 degrees C). Immunoblotting of microsomal fractions prepared from rat tissues using a polyclonal antibody raised against recombinant CYP2J2 that cross-reacted with CYP2J3 but not with other known rat P450s demonstrated abundant expression of CYP2J3 protein in heart and liver. Immunohistochemical staining of formalin-fixed paraffin-embedded rat heart tissue sections using the anti-CYP2J2 IgG and avidin-biotin-peroxidase detection localized expression of CYP2J3 primarily to atrial and ventricular myocytes. In an isolated-perfused rat heart model, 20 min of global ischemia followed by 40 min of reflow resulted in recovery of only 44 +/- 6% of base-line contractile function. The addition of 5 microM 11, 12-epoxyeicosatrienoic acid to the perfusate prior to global ischemia resulted in a significant 1.6-fold improvement in recovery of cardiac contractility (69 +/- 5% of base line, p = 0.01 versus vehicle alone). Importantly, neither 14,15-epoxyeicosatrienoic acid nor 19-hydroxyeicosatetraenoic acid significantly improved functional recovery following global ischemia, demonstrating the specificity of the biological effect for the 11, 12-epoxyeicosatrienoic acid regioisomer. Based on these data, we conclude that (a) CYP2J3 is one of the predominant enzymes responsible for the oxidation of endogenous arachidonic acid pools in rat heart myocytes and (b) 11,12-epoxyeicosatrienoic acid may play an important functional role in the response of the heart to ischemia.
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PMID:Molecular cloning, expression, and functional significance of a cytochrome P450 highly expressed in rat heart myocytes. 913 7

Numerous factors are involved in the spread of secondary damage in spinal cord after traumatic injury, including ischemia, edema, increased excitatory amino acids, and oxidative damage to the tissue from reactive oxygen species. Neutrophils and macrophages can produce reactive oxygen species when activated and thus may contribute to the lipid peroxidation that is known to occur after spinal cord injury. This study examined the rostral-caudal distribution of neutrophils and macrophages/microglia at 4, 6, 24, and 48 h after contusion injury to the T10 spinal cord of rat (10 g weight, 50 mm drop). Neutrophils were located predominantly in necrotic regions, with a time course that peaked at 24 h as measured with assays of myeloperoxidase activity (MPO). The sharpest peak of MPO activity was localized between 4 mm rostral and caudal to the injury. Macrophages/microglia were visualized with antibodies against ED1 and OX-42. Numerous cells with a phagocytic morphology were present by 24 h, with a higher number by 48 h. These cells were predominantly located within the gray matter and dorsal funiculus white matter. The number of cells gradually declined through 6 mm rostral and caudal to the lesion. OX-42 staining also revealed reactive microglia with blunt processes, particularly at levels distant to the lesion. The number of macrophages/microglia was significantly correlated with the amount of tissue damage at each level. Treatments to decrease the inflammatory response are likely to be beneficial to recovery of function after traumatic spinal cord injury.
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PMID:Acute inflammatory response in spinal cord following impact injury. 958 56

For functional recovery after spinal cord injury, regenerating fibres need to grow and to reform appropriate connections with their targets. The isolated central nervous system of neonatal opossums aged 1-9 days has been used to analyse the precision with which neurons become reconnected during regeneration. In culture these preparations maintain their electrical activity and show rapid outgrowth through spinal cord crushes or cuts. By recording electrically and by staining with horseradish peroxidase, we first demonstrated that direct reflex connections were already present at birth between sensory fibres in one segment and motoneurons in the same segment and in adjacent segments. As in previous experiments, 5 days after the spinal cord had been crushed, labelled sensory fibres grew across the lesion to reach the next segment (Woodward et al. (1993) J. Exp. Biol., 176, 77-88; Varga et al. (1995a) Eur. J. Neurosci., 7, 2119-2129, Varga et al. (1995b) Proc. Natl. Acad. Sci. USA, 92, 10959-10963). Beyond the lesion the labelled axons abruptly changed direction, traversed the spinal cord and terminated on labelled motoneurons in the ventral horn. In preparations that had regenerated dorsal root stimulation once again initiated ventral root reflexes. Electron micrographs revealed synapses made by labelled sensory axons on motoneurons. Double staining of growing sensory axons and radial glial fibres showed close association, suggesting guidance. These results indicate that the original pathway is re-established during repair and that appropriate connections are reformed after injury.
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PMID:Re-establishment of direct synaptic connections between sensory axons and motoneurons after lesions of neonatal opossum CNS (Monodelphis domestica) in culture. 976 81

The purpose of this study was to observe functional recovery and motoneuron death after nerve transection-and-repair in neonatal versus young animals. One hundred nine Lewis rats underwent posterior tibial nerve transection-and-repair at 6 or 22 days of age. Fifty-two and fifty-seven nerves at the 6- and 22-day times were used for endpoint analysis at 1, 3, 10, and 14 months. These assessments included serial functional walking track analysis, electrophysiologic studies, muscle mass evaluation, motoneuron counts with retrograde horseradish peroxidase tracing, and histologic and morphometric nerve analysis. Walking track analysis and nerve conduction velocity indicated significantly poorer functional regeneration in the 6-day-old group than in the 22-day-old group. Muscle mass in the 6-day-old group did not recover as well as in the 22-day-old group. Motoneuron numbers stained with horseradish peroxidase were less in the 6-day-old group than in the 22-day-old group. In contrast, morphometric analysis did not reach significance. This study suggests that the same nerve injury sustained in a neonatal rat is less likely to demonstrate functional recovery than one sustained in a young rat.
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PMID:Long-term observation of the effect of peripheral nerve injury in neonatal and young rats. 981 Oct 5

The present study examined regeneration and restoration of function of the mammalian central vestibular system in the infant rat. The lateral vestibulospinal tract (LVST) of rats was completely transected unilaterally by a ventral approach. After a postoperative interval of one day to three months, the LVST was examined by anterograde transport of wheat-germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) and retrograde transport of fluorescent dye. Twelve of the 22 LVST-transected rats showed successful regeneration. The regenerated fibers formed a compact fiber bundle, which sent terminals to their normal targets. The contribution of the regenerated fibers to functional recovery was estimated by analyzing the locomotor capacity of the transected rats. The locomotor movements were measured on the surface of a digitizer table by attaching a miniature resonance coil to the abdomen of the rats. Rats which shows normal locomotor movements represented a marked regeneration of LVST fibers. In contrast, rats with poorly-controlled locomotor movements showed unsuccessful regeneration. These results suggest that, contrary to previous thought, regeneration and functional restoration of the central vestibular system in young rats does occur.
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PMID:Axonal regeneration with functional restoration in the vestibulospinal tract in young rats. 985 22

We studied the effects of insulin-like growth factor I on Achilles tendon healing in a rat model. Rats were randomized into groups of six each: sham surgery, transection alone, and transection plus growth factor. Postoperatively, rats treated with growth factor had a significantly smaller maximum functional deficit and a decreased time to functional recovery than rats in the untreated groups. Biomechanical testing revealed no significant differences in the measured parameters between the treated and the untreated groups after transection. To study the mechanism of action, six additional animals received an Achilles tendon injection of the inflammatory agent carrageenan alone and six received carrageenan plus growth factor. Rats treated with growth factor did not show the inflammation-induced functional deficit experienced by the control rats. Spectrometric myeloperoxidase assays on the remaining eight rats after Achilles tendon transection demonstrated no significant difference between the untreated and the growth factor-treated groups, indicating a mechanism other than neutrophil recruitment by which the growth factor limits inflammation. Histologic studies were performed on carrageenan-injected rats at postinjection day 2 and on surgically treated rats at postoperative day 15. No gross histologic differences were seen between untreated and growth factor-treated groups. This study demonstrated that via a possible antiinflammatory mechanism, insulin-like growth factor I reduces maximum functional deficit and accelerates recovery after Achilles tendon injury.
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PMID:Insulin-like growth factor I accelerates functional recovery from Achilles tendon injury in a rat model. 1035 75

Nitecapone (NC) has been shown to have beneficial effects on the functional recovery of rat hearts in Langendorff-preparation. The present study was executed to evaluate the effect of NC on preservation of grafts in heart transplantation and the role of NC in the inhibition of granulocyte infiltration. Donor hearts were perfused and stored at +4 degrees C for 8 h in either Ringer solution in the control-group (C-group, n = 26) or in NC (50 microM) added Ringer solution (NC-group, n = 18). The heterotopic heart transplantation was performed. The rats in both groups were killed at either 10 min or 60 min after release of the aortic clamp and tissue samples were obtained for antioxidative capacity, myeloperoxidase activity, and lipid peroxidation measurements. In vitro studies were performed using sodium azide or nitecapone to inhibit myeloperoxidase (MPO) activity of isolated human leukocytes. A total of 61% of the grafts began to beat in the NC-group, compared to 46% in the control group. Using an arbitrary scale of functional performance, only 33% (4/12) of the grafts were classified as well functioning in the control group, compared to 82% (9/11) in the NC-group (P<0.05). MPO activity was equal in both groups after 10 min but significantly lower after 60 min in the NC-group as compared to the control group (P<0.05). In vitro studies demonstrated that NC inhibits 50% of purified MPO activity at a concentration of 10 microM. NC did not significantly affect lipid peroxidation or the preservation of endogenous antioxidants. Since NC inhibited myeloperoxidase both in vitro and in vivo, it seems that the positive effects of NC on graft preservation may be mediated via the inhibition of granulocyte infiltration.
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PMID:Nitecapone inhibits myeloperoxidase in vitro and enhances functional performance after 8 h of ischemia in experimental heart transplantation. 1036 86

Intraspinally implanting a nerve autograft (NAG) to promote axonal regeneration toward periphery was investigated as a surgical treatment for spinal cord injury in adult rats. Fifteen animals underwent a left hemisection of the spinal cord at T12 level and an intradural section of all ipsilateral lumbar ventral roots. In repaired animals (n = 9), the electrophysiologically selected left L3 and L4 lumbar ventral roots supplying the quadriceps muscle were anastomosed to a NAG. The NAG was taken from the right peroneal nerve and then ventrolaterally implanted into the cord at a level 7 mm rostral to the hemisection. In the control group (n = 6), sectioned lumbar ventral roots were left unrepaired. Nine months later, the animals were assessed with clinical, electrophysiological, and histological examinations. Muscle action potential and motor evoked potential were obtained from the denervated/reinnervated quadriceps in all repaired animals, with a mean amplitude of 918.3+/-328.9 microV and 215.8+/-39.7 microV, respectively. Horseradish peroxidase retrograde labeling from the denervated/repaired lumbar ventral roots, performed in five repaired animals, showed that the mean of labeled neurons, ipsilaterally located in the thoracic ventral horn near the implantation site, was 145.8+/-111.7. Histological analysis showed numerous myelinated axons in the NAG and denervated/repaired lumbar ventral roots of all repaired animals. The study of neuromuscular junctions furthermore confirmed numerous newly formed endplates appearing in the denervated/reinnervated quadriceps. These changes were absent in the control animals. These data indicate that the rostral thoracic spinal motoneurons can innervate the caudal denervated/repaired lumbar ventral roots and the target quadriceps via an implanted NAG, thereby inducing some functional recovery in adult rats after lower thoracic spinal cord injury.
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PMID:Reinnervation of denervated lumbar ventral roots and their target muscle by thoracic spinal motoneurons via an implanted nerve autograft in adult rats after spinal cord injury. 1036 17

The acellular nerve graft was utilised to restore a functional reinnervation of the biceps brachii muscle from the motoneuron pool of the cervical spinal cord. The musculocutaneous nerve stump was sutured to an acellular nerve graft, the opposite end of which was inserted into the cervical spinal cord cranial to the avulsed C5 ventral root. The acellular nerve graft was repopulated by Schwann cells heavily immunostained for NGFr within 90 days. The Schwann cells migrating from the nerve stump reached the spinal cord grey matter, where they stimulated the motoneurons to send axonal sprouts. The functional reinnervation of the biceps brachii muscle was assessed by means of the behavioural (grooming) test and EMG, the presence of myelinated and unmyelinated axons was demonstrated by light and electron microscopy. The axonal reconnection of the musculocutaneous nerve stump was verified by horseradish peroxidase retrograde labelling of the spinal motoneurons. Moreover, the motoneurons on the operated side of the C5 spinal segment displayed increased immunostaining for GAP-43 in comparison to the contralateral side, whereas the pattern of AChE histochemical reaction was similar on both the operated and contralateral side, of the C5 segment 150 days after acellular graft implantation. The regenerated axons bridged a 4-cm long originally acellular nerve graft to reach and reinnervate the biceps brachii muscle. The reinnervation of the neuromuscular junctions was morphologically determined by immunofluorescence for neurofilaments. The number of myelinated axons in the acellular nerve graft was significantly higher than those growing over the cellular graft, but their diameter was smaller. The results of experiments presented here demonstrate functional recovery of the biceps muscle reinnervation through the acellular nerve graft repopulated by migrating Schwann cells. The process of reinnervation by acellular nerve graft is however delayed and worse in comparison with the cellular graft.
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PMID:Acellular nerve graft re-seeded by Schwann cells migrating from the nerve stump can stimulate spinal motoneurons for functional reinnervation of the rat muscle. 1075 79

Intravenous administration of phenylephrine provokes a pattern of cellular activation in the nucleus of the solitary tract that resembles the central distributions of primary baroreceptor afferents supplied by the carotid sinus and aortic depressor nerves. Transganglionic transport and denervation methods were used in an experimental setting to test the dependence of phenylephrine-induced Fos immunoreactivity on the integrity of buffer nerve afferents, and to identify the subregions of the nucleus of the solitary tract supplied by each. Cholera toxin B-horseradish peroxidase injections into either or both nerves revealed terminal labeling concentrated in, but not restricted to, the dorsal commissural part of the nucleus of the solitary tract at the level of the apex of calamus scriptorius, and extending into the dorsal subnucleus at the level of the area postrema. Preferential ramifications of carotid sinus and aortic depressor nerve afferents at the levels of the commissural part of the nucleus and the area postrema, respectively, were reflected in the extent to which labeled fibers comingled with neurons exhibiting phenylephrine-induced Fos in dual labeling experiments. Complete sinoaortic denervation reduced by 90% the number of neurons exhibiting drug-induced Fos expression. Selective carotid and aortic sinus denervations effected partial reductions manifest preferentially in the caudal and rostral foci of the distribution, respectively. Reduced activational responses at the level of the area postrema of aortic sinus-denervated rats were accompanied by a reduction in cellular nicotinamide adenine dinucleotide phosphate-diaphorase activity in this region. Animals killed 30 days after complete sinoaortic denervation displayed no evidence of recovery of phenylephrine-induced Fos, while the strength and distribution of the response in rats that received selective carotid sinus denervation were indistinguishable from those seen in controls. These findings (i) support the dependence of phenylephrine-induced Fos expression on the integrity of carotid sinus and aortic depressor nerve afferents, (ii) provide anatomical and functional evidence that the two buffer nerves distribute differentially within the nucleus of the solitary tract, and (iii) implicate central reorganization as a likely basis for functional recovery of baroreflex mechanisms following partial sinoaortic denervation.
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PMID:Effects of selective sinoaortic denervations on phenylephrine-induced activational responses in the nucleus of the solitary tract. 1106 45


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