Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular diseases like thrombosis, myocardial infarction, cerebral ischemia or chronic venous insufficiency affect a high proportion of the population. They are all associated with more or less pronounced ischemic conditions. We have previously shown that some venotropic drugs display an anti-ischemic activity, i.e. they prevent the hypoxia-induced decrease in ATP content in cultured cells. The effect is due to the fact that these molecules maintain mitochondrial respiratory activity during hypoxia. Among them is bilobalide. Starting from the 3D structure of bilobalide, we designed new molecules presenting the same chemical features. They were synthesized and tested for their biological activity. As the parent compound, two of them, malonic acid dicyclopent-2-enyl ester (MRC2P119) and 2-oxo-3-oxa-bicyclo[3.1.0]hexane-1-carboxylic acid allyl ester (MRC2P57), were able to markedly increase the respiratory control ratio of isolated mitochondria. They are able to prevent the inhibition of complex I by amytal and of complex III by myxothiazol, but not the uncoupling of the respiration by carbonylcyanide m-chlorophenyl hydrazone (m-CCP). Moreover, MRC2P119 and MRCP2P57 inhibit, in a dose-dependent way, the hypoxia-induced decrease in ATP content in endothelial cells as well as the subsequent activation of these cells as evidenced by an inhibition of the increase in neutrophil adherence to the endothelial cells induced by hypoxia. Finally, MRC2P119 prevent the hypoxia- and the hypoxia-reoxygenation-induced decrease in viability of SH-SY5Y neuroblastoma cells. In conclusion, we identified two new molecules, which display anti-ischemic properties when tested in vitro on endothelial and neuronal cell types. This anti-ischemic activity is probably due to a protection of complexes I and III of the mitochondrial respiratory chain.
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PMID:Mitochondrial respiratory chain as a new target for anti-ischemic molecules. 1200 18

Pressure in the central nervous system (CNS) depends upon the volume of tissue that it contains. This includes blood, cerebrospinal fluid (CSF), nerves and any space occupying lesions. The dependency of pressure on volume arises because the CNS is confined by bone. Venous and CSF pressure is linked to overall pressure. Arterial pressure can increase in response to overall pressure to maintain arterial supply. Continuous arterial supply can be maintained because venous blood flows out of the CNS. Reduced volumes of arterial blood will enter the system if venous outflow is interrupted. Increase in CNS volume, as occurs with space occupying lesions, causes compression of veins. This may result in increased venous pressure and reduction in flow of blood out of the CNS. Cerebrospinal fluid (CSF) is extracellular fluid; its absorption back into the circulation is influenced by venous pressure. Any increased in CNS tissue volumes can therefore lead to CSF accumulation. This may then exacerbate the hydrocephalus by further increasing overall CNS volume. Free flow of CSF around the CNS facilitates venous drainage. Blockages to CSF flow can act like space occupying lesions. Chiari malformations, where the cerebellar tonsils obstruct the foramen magnum lead to reductions in CSF flow that can occur intermittently. This leads to impairment of venous drainage which may result in accumulation of CSF. The head or the spine can be affected together or separately. The manifestation of excess fluid accumulation is hydrocephalus and syringomyelia. The speed and origin of venous insufficiency influences the morphology of individual cases particularly with regard to lateral ventricle size. When pressure increases rapidly there may be little time for CSF accumulation. Oedema, compression of intracranial CSF spaces and cerebral ischaemia follows. When venous pressure is only slightly elevated CSF will accumulate and the manifestations of ischaemia may be less apparent, although ischaemia will be a feature of all instances of pathologically raised CNS pressure.
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PMID:The venous hypothesis of hydrocephalus. 1791 32