Dynamic Alteration Of Gene Expression Of The Platelet-derived Growth Factor On SAH With Late Proliferation Of Cerebral Wall In Rabbit

PrefaceCerebral vasospasm after subarachnoid hemorrhage often can cause severe brain tissue ischemia or delayed ischemic brain damage. CVS was biphasic, one for early-onset, more common in SAH, after 0.5 h～3 d, also known as acute CVS, the other is the delayed cerebral vasospasm (DCVS), after bleeding in 4～15 days happened, to the peak after 7～10 days. DCVS is the most common cause of delayed cerebral ischemia,because of the Vascular is poorly response to vasodilator,and difficult to reverse. Studies have suggested that DCVS after SAH is due to pathological changes in blood vessels rather than functional spasm. Autopsy studies after SAH and cerebral vascular spasm Experimental studies have confirmed that the morphological changes of artery wall were very important at the cause of the latest CVS. Some scholars found that platelet-derived growth factor (PDGF) can cause changes in cerebral blood wall proliferation in vivo and in vitro experiments. We detect PDGF in cerebral artery wall changes after SAH in gene transcription by RT-PCR, to explore the pathological mechanisms of PDGF after SAH and gene therapy.Materials and MethodsThe rabbits were randomly divided into control group, SAH 3 days group, SAH 7 days group. The model of SAH was induced by injecting blood into cistern. The control group (8): SAH 3 days group (9): executed after the second injection of blood drawn 1h; SAH 7 days group (9): executed after the second injection of blood drawn six days. The score of diet, activity and neurological function of each SAH group was recorded.Three rabbits in each group were used to make electron microscopic morphology and light microscopy. The remaining basilar arterys in each group were used to detected the expression of PDGF-mRNA by RT-PCR . Data analysis of variance test was used and the difference was significant(P <0.05). ResultsClinical symptoms of the rabbits increased at the threeth day after SAH and to the peak at the sevened day. Clot was foud in subarachnoid of every rabbit in SAH 3 days group and SAH 7days group, but not in the control group. The frame of basilar artery in the control group is normal by optical observation. The image of vascular wall thickening, luminal stenosis, smooth muscle cell proliferation significantly with disorder was observated optically in SAH 3 days group and SAH 7days group. Endothelial cells and smooth muscle cells of irregular shape were observated under electron microscopy and many cell surface processes mean transformed phenotype. PDGF mRNA expression in the basilar artery wall in control group is lower. PDGF mRNA transcription level of basilar artery wall in SAH 3 days group raised significantly,compared with the normal control (P <0.01). However there was no significant difference between control group and SAH 7 days group.ConclusionThe model of SAH induced by injecting twice-blood into cistern is stable and reliable and a good simulation of human SAH after CVS. DCVS after SAH is due to pathological changes in blood vessels rather than functional spasm, which is caused by a cerebral vascular proliferative disease. The high PDGF-mRNA expression may be related to the proliferation of blood vessels after SAH, and be one cause of delayed neurological deficit. Early application of antagonism of PDGF gene therapy may be a new idea.