Intervention Of Pentoxifylline To Leptomeningeal Fibrosis In Rabbits With Subarachnoid Hemorrhage

Objective Subarachnoid hemorrhage （SAH） is commonly a serious disease inthe field of neurology and neurosurgery, which has a high mortality and morbidity.Chronic hydrocephalus is one of the major complications of SAH, which seriouslyimpacts patients in quality of life and prognosis. Some studies have show that theformation of chronic hydrocephalus is associated with leptomeningeal fibrosis afterSAH. Pentoxifylline（PTX） is a non-specific phosphodiesterase inhibitor, which hassignificant anti-fibrotic effect. The objectives of this study are to investigate of theeffect of PTX on leptomeningeal fibrosis of rabbits with SAH and the relationshipbetween leptomeningeal fibrosis and transforming growth factor beta1（TGF-β₁） ofcerebrospinal fluid （CSF）.Methods Fifty clean-class New Zealand white rabbits were randomly dividedinto normal control group, sham operation group, SAH model group （SAH group）,PTX intervention group（PTX group）and PTX control group, the model of SAH wasestablished by injecting auto-blood into the cisterna magna. PTX was injected intocisterna magna of PTX group and PTX control group once a day for14days. At day3、day7、day11、day16and day21, the levels of TGF-β₁in CSF were measured. Onthe21stday, all rabbits were killed. The brain sample was taken for MASSON staining.Measure the thickness of leptomeninges and with CMIAS4.0/4.1image softwareprocessed image, use “100×thickness/gray value” index of the collagen fibercontent, observed the lepomeningeal fibrotic degree.Results The rabbits became anorectic and depressed after injecting blood intocisterma magna, eating were to reduce. After the rabbits were killed, observe the brain,There was blood clot in the subarachnoid space, especially in ventral aspect of brain,including brain basal cistern, circumvolution pavimentum cerebri main blood vessel.The levels of TGF-β₁in CSF have two peaks in model group and PTX group（P<0.05）, but the level of PTX group is significantly lower（P<0.05）. Normal control group, sham operation group and PTX control group were not obviouslychange. MASSON staining showed that the grayscale value of leptomeninges in modelgroup and PTX group was obviously lower than others, and thickness was obviouslyhigher. The gray scale of leptomeninges in PTX group was obviously higher than thatin model group, and thickness was obviously lower（P<0.05）. The gray scale andthickness of leptomeninges in normal control group, sham operation group and PTXcontrol group were not obviously change.Conclusion1. The levels of TGF-β₁in CSF were increasing by double phaseafter SAH.2. There was leptomeningeal fibrosis after SAH at the21stday.3. Following subarachnoid hemorrhage, PTX can decrease the levels of TGF-β₁inCSF, especially the second phase, and reduce leptomeningeal fibrosis.