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

Using a silver impregnation (argyrophil III) and immunohistochemistry, acute cytopathic features after cerebral ischemia were investigated. Additionally, functional recovery and interconnection between the host and graft was also explored after neural graft. Animals were embolized in unilateral middle cerebral artery for 1 h. Argyrophil III method demonstrated "collapsed" dark neurons in the striatum, cortex, reticular thalamus, amygdala, and hypothalamus on ischemic side. These neurons exhibited characteristic shrunken somata with corkscrew-like dendrites, suggesting changes in cytoskeletal protein. In the above mentioned areas, the loss of immunoreactivity for mu-calpain proenzyme and microtubule-associated protein 2 was also detected. Neural graft into the ischemic striatum was made 2 weeks after the ischemia paradign. The grafted striatal cells were prepared from E15 fetuses to make cell suspension marked by rhodamine-labeled latex microspheres. Methamphetamine-evoked rotations were detected after ischemia. These motor alterations were reduced gradually but significantly at 8 weeks after the graft. Interconnecton between the host and grafted cells was then studied in a brain slice preparation after loading fura-2 AM. About 10% of grafted cells tested from rats that showed motor amelioration exhibited [Ca2+]i increase to the electrical stimulation applied to the neighboring host tissue. Data indicate that, in the very early stage after ischemia, cytoskeletal damages, especially on microtubules, started and this would lead to later infarct. The graft survived in the ischemic striatum having connections with the host, and this might be partly involved in the amelioration of motor function.
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PMID:Early cytopathic features in rat ischemia model and reconstruction by neural graft. 863 48

Cardiac tissue undergoes changes during ischemia-reperfusion (I-R) that compromise its normal function. Cell death is one of the consequences of such damage, as well as diminution in nitric oxide (NO) content. This signaling molecule regulates the function of the cardiovascular system through dependent and independent effects of cyclic guanosine monophosphate (cGMP). The independent cGMP pathway involves post-translational modification of proteins by S-nitrosylation. Studies in vitro have shown that NO inhibits the activity of caspases and calpains through S-nitrosylation of a cysteine located in their catalytic site, so we propose to elucidate if the regulatory mechanisms of NO are related with changes in S-nitrosylation of cell death proteins in the ischemic-reperfused myocardium. We used two compounds that increase the levels of NO by different mechanisms: Prolame, an amino-estrogenic compound with antiplatelet and anticoagulant effects that induces the increase of NO levels in vivo by activating the endothelial nitric oxide synthase (eNOS) and that has not been tested as a potential inhibitor of apoptosis. On the other hand, S-Nitroso-N-acetylpenicillamine (SNAP), a synthetic NO donor that has been shown to decrease cell death after inducing hypoxia-reoxygenation in cell cultures. Main experimental groups were Control, I-R, I-R+Prolame and I-R+SNAP. Additional groups were used to evaluate the NO action pathways. Contractile function represented as heart rate and ventricular pressure was evaluated in a Langendorff system. Infarct size was measured with 2,3,5-triphenyltetrazolium chloride stain. NO content was determined indirectly by measuring nitrite levels with the Griess reaction and cGMP content was measured by Enzyme-Linked ImmunoSorbent Assay. DNA integrity was evaluated by DNA laddering visualized on an agarose gel and by Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling assay. Activities of caspase-3, caspase-8, caspase-9 and calpain-1 were evaluated spectrophotometrically and the content of caspase-3 and calpain-1 by western blot. S-nitrosylation of caspase-3 and calpain-1 was evaluated by labeling S-nitrosylated cysteines. Our results show that both Prolame and SNAP increased NO content and improved functional recovery in post-ischemic hearts. cGMP-dependent and S-nitrosylation pathways were activated in both groups, but the cGMP-independent pathway was preferentially activated by SNAP, which induced higher levels of NO than Prolame. Although SNAP effectively diminished the activity of all the proteases, a correlative link between the activity of these proteases and S-nitrosylation was not fully established.
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PMID:Cardioprotective effects of Prolame and SNAP are related with nitric oxide production and with diminution of caspases and calpain-1 activities in reperfused rat hearts. 3139 96