| At present the incidence rate of ischemic cerebrovascular diseaseis increasing gradually. Precaution and treat has attracted more andmore attention of the medicine field because of high inability rate. Thepathologic change of ischemic cerebrovascular disease includes that:blood is high coagulation high adhesion and high assembly, cerebralblood flow decreases, ischemia hypoxygeon, abnormal energemetabolism and oxidant radical produces,inflammartary factor and cellsparticipates in and so on, at last leading to neurons death.These providepathologic basis for finding out efficient medication for treating ischemiccerebrovascular disease. Following gradual deep study about the whitematter, we found that neural function covery after cerebral ischemia liesin not only the gray matter protection, but also the white matter, not onlyneuron are cared , but aso glial. Traditional conception of onlyprotecting neuron was changed, from simple neuron protection to globleprotection. Neural function covery after cerebral ischemia lies in not onlypreserving neuronal perikarya,but also depending on nerve fiber.But atpresent the study on medicine for the white matter protection is less.Some attraction from the traditional Chinese medicine such asflavonoids saponins of panax natoginseng and coumarin can improvecirculation for increasing cerebral blood flow and anti-assembly ofplatelet anti-coagulation anti-inflammation cleaning out oxidant andadjusting serum lipids. These functions have non-substitutive action intreating ischemic cerebrovascular disease. Daphnetin, the derivative ofcoumarin , is used for treating ischemic heart disease thromboangitisobliterans and precauting atherosclerosis because it can expand bloodvessel strengthen cardiac muscle anti-coagulation(anti-vimentinK)anti-assembly of platelet bearing hypoxia decreasing total cholesterolincreasing high dencity lipoprotein cholesterol, that it is little toxicity andside effect, it is metabolized and drained quickly. Daphnetin is centralrestrain ,simultaneously it can get across blood brain barrier so wehypothesize it has same function in central nercous system,namelycerebral protection. But we didn't find clinical and experimental reportabout daphnetin for treating ischemic cerebrovascular disease. Astrocyte, macroglial in brain, has important function in neuron'sdevelopment, growth ,directional movement, resuming function afterinsult. At present,people have transferred attention from neuron to glialcell. The change and effect of astrocyte are adventage anddisadventage character after cerebral ischemia: one its activation andhyperplasia is usefull in balance of white and electrolyte, metabolism ofneurotransmitter, metabolism of energy removing necrotic matter,secreting neuron growth factor; on the other hand it may be unfavorablein neuron recover because it occupies some room to physical barrier,block axon extension, secret neural growth inhibitor factor for excesshyperplasia and activation(reactivate glial), so modulating astrocyte'sfunction is very important in different course. Glial fibrilliary acidicprotein (GFAP) is component of astrocyte's cytoskeleton (intermediatefilament),as characteristic remark of mature and reactiveastrocyte,GFAP is studied astrocyte's change , its limited expression isastrocyte effect basis. Astrocyte in white matter is primary fibrousastrocyte, how its change and special function are after cerebralischemia , what kind of effect on axon regeneration when astrocytefunction is intervented, we have known little until now. In this experiment, we made model of forebrain ischemia byrepeated occluding rat's both common carotid arteries imitatinghuman cerebral ischemia, irrigated rats daphnetin after surgery,removed brain in different time for GFAP immunohistochemistry study,observed GFAP of astrocyte in white matter regions. We found GFAPexpression in corpus callosum and internal capsule in treating groupusing daphnetin was higher than control group and sham group on 2thand 4th week (P <0.05), decreased on 6th week and approximatelynatrurally(P >0.05). GFAP expression in region around ventricleincreased in comparison to control group and sham group on 2th week(P <0.05), lowered on 4th week,but there is not difference incomparison to sham group(P >0.05); it is lower than sham group on6th remarkably(P<0.05). In different time, GFAP expression in treatinggroup using daphnetin is gradually decreasing in all region, difference isremarkably(P<0.05). We can find from experiment: treating using daphnetin aftercerebral ischemia , GFAP expression in white matter region wasincreased in early stage and gradually decreased following time fortreating, difference is remarkably(P<0.05).That indicates daphnetin hasdifferent effect on GFAP expression in different cerebral region,this maybe relevant to astrocyte differene and reactivation in region. Definition isGFAP expression in all region increased on 2th week, it affirmsdaphnetin increases GFAP expression on 2th week, this is key time toneural function recoverer. Astrocyte activation and hyperplasia is usefull.The form of glial scar after cerebral ischemia is complex,it is relevant toischemic degree ,duration, area,intervention measures and so on. Itsthought defnetin time is from about 2 week after local cerebral ischemia,it is remarkabe in 4 week. Some neural inhibitor factor expression inextracellular matrix begins to increase after 1 week. In the present study,following time extent for treating after cerebral ischemia,GFAPexpression decreased gradually, astrocyte proliferation alleviated andactivator decreased, reactive glial alleviated,it could reduce secret ofaxon inhibitor,and inhibit glial scar, all these are available to axonregeneration and neural function recovery . The mechanism thatdaphnetin affects GFAP expression could be daphnetin can expandblood vessel, anti-coagulation ,inhibit thrombus form, increase cerebralflow, alleviate ischemic insult of brain or directly activates astrocyte inearly stage after cerebral ischemia, in later stage it may be relevant todaphnetin inhibitor on protein kinases and also it may be programmecell death of astrocyte after excess activation during cerebral ischemia .The mechanism that daphnetin affects astrocyte need to be studieddeeply .Because pathologic change after cerebral ischemia is verycomplex, the time that treating using daphnetin results in GFAP changein white matter regions is close related to neural function recovery in theexperiment.I think the time of treating using daphnetin is about 4 week,it can be determined depending on clinical neural function recovery. Difference between time and space in GFAP expression in whitematter regions after cerebral ischemia reflects astrocyte function,astrocyte morphology, size and number is relevant to ischemic time,position and intervention measure. Reactive astrocyte is responsible toischemic insult and neural function recovery, it prompts axonregeneration by substance exchange,secreting neuron growth factor,cytokine identifiction factor and helps recover neural system normalfunction, so in a certain stage, increase of GFAP expression issignificant to neural protection and function recovery after cerebralischemia. But at the same time excess GFAP expression will leads toformation of glial scar, this will block axon regeneration. In the presentstudy, daphnetin accelerates GFAP expression in white matter regionsin early stage after cereral ischemia and exhibits distinct inhibitor in laterstage, this is identical to neural function restory in different stage aftercerebral ischemia. All these provides experimental basis for daphnetinon clinic application after cerebral ischemia. So interventing glial cellfunction and trying to improve bad regenerative environment of centralneural system are not only basic and clinical scientists only way incapturing disease in central neural system,but also provide rightdirection to explore and study new medication for prompting centralneural regeneration. |
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