Experimental therapy of a platelet-activating factor antagonist (ginkgolide B) on photochemically induced thrombotic cerebral ischaemia in tree shrews.
1. The aim of the present study was to investigate the effects of a platelet-activating factor (PAF) antagonist (ginkgolide B; GB) on brain oedema, ion homeostasis, monoamine neurotransmitter disturbances in ischaemic penumbra and the neuroprotective mechanisms of the PAF antagonist. 2. Photochemically induced thrombotic cerebral ischaemia in tree shrews was used as the experimental model and changes in histopathology and the content of monoamine neurotransmitters (measured by a spectrofluorometer), water content (measured by a specific gravimetric method), sodium and calcium (measured by an atomic absorption spectrophotometer) in the penumbra were observed. 3. Results show that content of noradrenaline (NA), dopamine (DA) and 5-hydroxytryptamine (5-HT) decreased in the penumbra, while 5-HT metabolite 5-hydroxyindole-3-acetic acid, sodium, calcium and water contents increased markedly (P < 0.01) after photochemical reaction. 4. In tree shrews treated with GB (5 mg/kg, i.v.) 6 h after photochemical reaction, cortical NA, DA and 5-HT contents recovered to control levels and water and calcium contents decreased significantly (P < 0.01). 5. The results suggest that PAF may play an important role in inducing calcium overload, brain oedema and secondary brain damage in penumbra and that GB produces its neuroprotective effects by inhibiting the pathological manifestation of PAF.
Li
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Department of Pathophysiology, Kunming Medical College, China. faokmc@public.km.yn.cn
Meng
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Q
Zhang
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D000818:Animals; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004195:Disease Models, Animal; D004224:Diterpenes; D005260:Female; D046934:Ginkgolides; D020767:Intracranial Thrombosis / Q000150:complications / Q000209:etiology / Q000378:metabolism; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D014418:Tupaiidae
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D018696:Neuroprotective Agents; D010972:Platelet Activating Factor; C045856:ginkgolide B