Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The goal of this investigation was to determine whether hyaluronidase administration can alter the size, morbidity, and mortality of experimental acute cerebral infarctions. Accordingly, the left common carotid artery was occluded in 1205 ether-anesthetized Mongolian gerbils. The gerbils were randomized into hyaluronidase-treated (4000 National Formulary units per kg., intravenously, 5 minutes after occlusion) or control groups. All were examined for clinical signs of cerebrovascular accident three times during the 24 hours and then decapitated, and each hemibrain was analyzed for its total creatine kinase activity. In the control group, 90 of 601 gerbils died, whereas in the hyaluronidase-treated group only 61 of 604 gerbils died. This reduction in mortality was highly significant (chi 2 = 6.53, p less than 0.02). In the surviving gerbils with cerebrovascular accidents, infarct size was calculated by creatine kinase depletion (normal right hemibrain creatine kinase minus infarcted left hemibrain creatine kinase divided by right hemibrain creatine kinase and corrected for "residual" (nondepletable) creatine kinase). In controls, infarct size was 36.5 +/- 1.8 per cent (n = 105), and in the hyaluronidase-treated gerbils it was significantly lower, 31.4 +/- 1.7 per cent (n = 117, p less than 0.05). Thus, in gerbils with experimental cerebrovascular accidents, hyaluronidase significantly reduced mortality (by one-third) and reduced "enzymatic" infarct size by 14.0 +/- 4.6 per cent (p less than 0.01).
 ...
PMID:Effect of hyaluronidase on experimental cerebral infarct size and mortality. 707 54

Rat hearts were preserved by simple storage for 18 h at 0-1 degree C and reperfused parabiotically with whole blood from a host rat. The preservation solutions used for flush perfusion and storage were the commercial solutions EuroCollins, HTK, or UW with or without adding 40 mg/l hyaluronidase or EuroFlush-Glutathione (EFG) solution, especially designed for prolonged heart storage. All solutions were filtered (0.45 micron) before use. The functional recovery was measured using a latex balloon in the left ventricle for LVP, dp/dt, and isotonic stroke volume. The metabolic recovery as well as the edema formation was determined from freeze-clamped myocardium at the end of reperfusion. In hearts preserved with hyaluronidase-containing solutions, the edema formation during reperfusion was reduced combined with an improvement in the coronary flow. Functional and metabolic recovery were improved in these hearts with significant increase in the stroke volume and ECP in all groups versus hearts preserved in the hyaluronidase-free basic solutions. The effectiveness of HTK preservation was significantly improved by hyaluronidase in all parameters measured in our study. The best functional and metabolic recovery was found in hearts preserved by HTK + H- or EFG-solution. Thus, preservation solutions containing hyaluronidase, especially HTK + H and EFG, seem best suited for the prolonged storage preservation of the heart.
 ...
PMID:Minimal amounts of hyaluronidase in HTK or UW solution substantially improve the recovery of preserved hearts. 895 82

Hyaluronic acid, a major component of the brain extracellular matrix, is a regulator of angiogenesis, cell differentiation and migration. We used the rat middle cerebral artery occlusion model to show hyaluronan accumulation in stroke-affected areas. Using reverse transcription-polymerase chain reaction and Western blotting we showed up-regulation of hyaluronidase-1 and 2 between 1 h and 21 days after stroke. Hyaluronidase-1 was up-regulated earlier than hyaluronidase-2. The hyaladherins, receptor for hyaluronan-mediated motility and CD44 were also increased after stroke. Using immunohistochemistry, we showed association of hyaluronidases 1/2 and hyaladherins with neurons in the infarcted and peri-infarcted regions and hyaluronidase-1 with microvessels. Hyaluronan synthesis and degradation in the stroke hemisphere might have an impact on neuronal survival, angiogenesis and general tissue remodelling after stroke.
 ...
PMID:Hyaluronan expression following middle cerebral artery occlusion in the rat. 1683 37

Glycosaminoglycans (GAGs) have been shown to be responsible for the interstitial fluid pressurization of articular cartilage and hence its compressive stiffness and load-bearing properties. Contradictory evidence has been presented in the literature on the effect of depleting GAGs on the friction properties of articular cartilage. The aim of this study was to investigate the effect of depleting GAGs on the friction and deformation characteristics of articular cartilage under different tribological conditions. A pin-on-plate machine was utilized to measure the coefficient of friction of native and chondroitinase ABC (CaseABC)-treated articular cartilage under two different models: static (4 mm/s start-up velocity) and dynamic (4 mm/s sliding velocity; 4 mm stroke length) under a load of 25 N (0.4 MPa contact stress) and with phosphate-buffered saline as the lubricant. Indentation tests were carried out at 1 N and 2 N loads (0.14 MPa and 0.28 MPa contact stress levels) to study the deformation characteristics of both native and GAG-depleted cartilage samples. CaseABC treatment rendered the cartilage tissue soft owing to the loss of compressive stiffness and a sulphated-sugar assay confirmed the loss of GAGs from the cartilage samples. CaseABC treatment significantly increased (by more than 50 per cent) the friction levels in the dynamic model (p < 0.05) at higher loading times owing to the loss of biphasic lubrication. CaseABC treatment had no effect on friction in the static model in which the cartilage surfaces did not have an opportunity to recover fluid because of static loading unlike the cartilage tissue in the dynamic model, in which translation of the cartilage surfaces was involved, ensuring effective biphasic lubrication. Therefore the depletion of GAGs had a smaller effect on the coefficient of friction for the static model. Indentation tests showed that GAG-depleted cartilage samples had a lower elastic modulus and higher permeability than native tissue. These results corroborate the role of GAGs in the compressive and friction properties of articular cartilage and emphasize the need for developing strategies to control GAG loss from diseased articular cartilage tissue.
 ...
PMID:The effect of glycosaminoglycan depletion on the friction and deformation of articular cartilage. 1833 13

Stroke is the dominant cause of sensorimotor disability that primarily affects the elderly. We now show that neuroplasticity and functional recovery after stroke is constrained by inhibitory chondroitin sulphates. In two blinded, randomized preclinical trials, degradation of chondroitin sulphate using chondroitinase ABC reactivated neuroplasticity and promoted sensorimotor recovery after stroke in elderly rats. Three days after stroke, chondroitinase ABC was microinjected into the cervical spinal cord to induce localized plasticity of forelimb sensorimotor spinal circuitry. Chondroitinase ABC effectively removed chondroitin sulphate from the extracellular matrix and perineuronal nets. Three different tests of sensorimotor function showed that chondroitinase ABC promoted recovery of forelimb function. Anterograde and retrograde tracing showed that chondroitinase ABC also induced sprouting of the contralesional corticospinal tract in the aged treated hemicord. Chondroitinase ABC did not neuroprotect the peri-infarct region. We show for the first time delayed chondroitinase ABC treatment promotes neuroanatomical and functional recovery after focal ischaemic stroke in an elderly nervous system.
 ...
PMID:Delayed treatment with chondroitinase ABC promotes sensorimotor recovery and plasticity after stroke in aged rats. 2239 94

Physical and chemical constraints imposed by the periinfarct glial scar may contribute to the limited clinical improvement often observed after ischemic brain injury. To investigate the role of some of these mediators in outcome from cerebral ischemia, we treated rats with the growth-inhibitory chondroitin sulfate proteoglycan neurocan, the growth-stimulating heparan sulfate proteoglycan glypican, or the chondroitin sulfate proteoglycan-degrading enzyme chondroitinase ABC. Neurocan, glypican, or chondroitinase ABC was infused directly into the infarct cavity for 7 d, beginning 7 d after middle cerebral artery occlusion. Glypican and chondroitinase ABC reduced glial fibrillary acidic protein immunoreactivity and increased microtubule-associated protein-2 immunoreactivity in the periinfarct region, and glypican- and chondroitinase ABC-treated rats showed behavioral improvement compared with neurocan- or saline-treated rats. Glypican and chondroitinase ABC also increased neurite extension in cortical neuron cultures. Glypican increased fibroblast growth factor-2 expression and chondroitinase ABC increased brain-derived neurotrophic factor expression in these cultures, whereas no such effects were seen following neurocan treatment. Thus, treatment with glypican or enzymatic disruption of neurocan with chondroitinase ABC improves gross anatomical, histological, and functional outcome in the chronic phase of experimental stroke in rats. Changes in growth factor expression and neuritogenesis may help to mediate these effects.
 ...
PMID:Intracerebral chondroitinase ABC and heparan sulfate proteoglycan glypican improve outcome from chronic stroke in rats. 2261 73

Chondroitin sulphate proteoglycans (CSPGs) are extracellular matrix molecules whose inhibitory activity is attenuated by the enzyme chondroitinase ABC (ChABC). Here we assess whether CSPG degradation can promote compensatory sprouting of the intact corticospinal tract (CST) following unilateral injury and restore function to the denervated forelimb. Adult C57BL/6 mice underwent unilateral pyramidotomy and treatment with either ChABC or a vehicle control. Significant impairments in forepaw symmetry were observed following pyramidotomy, with injured mice preferentially using their intact paw during spontaneous vertical exploration of a cylinder. No recovery on this task was observed in vehicle-treated mice. However, ChABC-treated mice showed a marked recovery of function, with forelimb symmetry fully restored by 5 weeks post-injury. Functional recovery was associated with robust sprouting of the uninjured CST, with numerous axons observed crossing the midline in the brainstem and spinal cord and terminating in denervated grey matter. CST fibres in the denervated side of the spinal cord following ChABC treatment were closely associated with the synaptic marker vGlut1. Immunohistochemical assessment of chondroitin-4-sulphate revealed that CSPGs were heavily digested around lamina X, alongside midline crossing axons and in grey matter regions where sprouting axons and reduced peri-neuronal net staining was observed. Thus, we demonstrate that CSPG degradation promotes midline crossing and reinnervation of denervated target regions by intact CST axons and leads to restored function in the denervated forepaw. Enhancing compensatory sprouting using ChABC provides a route to restore function that could be applied to disorders such as spinal cord injury and stroke.
 ...
PMID:Chondroitinase ABC promotes compensatory sprouting of the intact corticospinal tract and recovery of forelimb function following unilateral pyramidotomy in adult mice. 2306 34

Ischemic stroke insults may lead to chronic functional limitations that adversely affect patient movements. Partial motor recovery is thought to be sustained by neuronal plasticity, particularly in areas close to the lesion site. It is still unknown if treatments acting exclusively on cortical plasticity of perilesional areas could result in behavioral amelioration. We tested whether enhancing plasticity in the ipsilesional cortex using local injections of chondroitinase ABC (ChABC) could promote recovery of skilled motor function in a focal cortical ischemia of forelimb motor cortex in rats. Using the skilled reaching test, we found that acute and delayed ChABC treatment induced recovery of impaired motor skills in treated rats. vGLUT1, vGLUT2, and vGAT staining indicated that functional recovery after acute ChABC treatment was associated with local plastic modification of the excitatory cortical circuitry positive for VGLUT2. ChABC effects on vGLUT2 staining were present only in rats undergoing behavioral training. Thus, the combination of treatments targeting the CSPG component of the extracellular matrix in perilesional areas and rehabilitation could be sufficient to enhance functional recovery from a focal stroke.
...
PMID:Perilesional treatment with chondroitinase ABC and motor training promote functional recovery after stroke in rats. 2396 Feb 8

Focal cerebral infarction causes secondary damage in the ipsilateral ventroposterior thalamic nucleus (VPN). Chondroitin sulfate proteoglycans (CSPGs) are a family of putative inhibitory components, and its degradation by chondroitinase ABC (ChABC) promotes post-injury neurogenesis. This study investigated the role of ChABC in the primary and secondary injury post stroke in hypertension. Renovascular hypertensive Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO), and were subjected to continuous intra-infarct infusion of ChABC (0.12 U/d for 7 days) 24 h later. Neurological function was evaluated by a modified neurologic severity score. Neurons were counted in the peri-infarct region and the ipsilateral VPN 8 and 14 days after MCAO by Nissl staining and NeuN labeling. The expressions of CSPGs, growth-associated protein-43 (GAP-43) and synaptophysin (SYN) were detected with immunofluorescence or Western blotting. The intra-infarct infusion of ChABC, by degrading accumulated CSPGs, rescued neuronal loss and increased the levels of GAP-43 and SYN in both the ipsilateral cortex and VPN, indicating enhancd neuron survival as well as augmented axonal growth and synaptic plasticity, eventually improving overall neurological function. The study demonstrated that intra-infarct ChABC infusion could salvage the brain from both primary and secondary injury by the intervention on the neuroinhibitory environment post focal cerebral infarction.
 ...
PMID:Neuroprotective effect of chondroitinase ABC on primary and secondary brain injury after stroke in hypertensive rats. 2432 94

Neuroanatomically connected regions distal to a cortical stroke can exhibit both degenerative and adaptive changes during recovery. As the locus for afferent somatosensory fibres and efferent motor fibres, the spinal cord is ideally situated to play a critical role in functional recovery. In contrast to the wealth of research into cortical plasticity after stroke, much less focus has previously been placed on the role of subcortical or spinal cord plasticity in recovery of function after cortical stroke. Little is known about the extent and spatiotemporal profile of spinal rewiring, its regulation by neurotrophins or inflammatory cytokines, or its potential as a therapeutic target to improve stroke recovery. This commentary examines the recent findings by Sist et al. (2014) that there is a distinct critical period of heightened structural plasticity, growth factor expression, and inflammatory cytokine production in the spinal cord. They suggest that neuroplasticity is highest during the first two weeks after stroke and tapers off dramatically by the fourth week. Spinal cord plasticity correlates with the severity of cortical injury and temporally matches periods of accelerated spontaneous recovery of skilled reaching function. The potential of treatments that extend or re-open this window of spinal cord plasticity, such as anti-Nogo-A antibodies or chondroitinase ABC, to dramatically improve recovery from cortical stroke in clinical populations is discussed.
...
PMID:Thinking outside the brain: structural plasticity in the spinal cord promotes recovery from cortical stroke. 2429 Dec 54


1 2 Next >>