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首页> 外文期刊>Journal of clinical neuroscience: official journal of the Neurosurgical Society of Australasia >Effect of pretreatment with a tyrosine kinase inhibitor (PP1) on brain oedema and neurological function in an automated cortical cryoinjury model in mice
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Effect of pretreatment with a tyrosine kinase inhibitor (PP1) on brain oedema and neurological function in an automated cortical cryoinjury model in mice

机译：酪氨酸激酶抑制剂（PP1）预处理对小鼠自动皮层冷冻损伤模型中脑水肿和神经功能的影响

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摘要

Cerebral oedema is a significant cause of morbidity in neurosurgical practice. To our knowledge, there is no ideal drug for prevention or treatment of brain oedema. Based on the current understanding of the pathogenesis of brain oedema, tyrosine kinase inhibitors could have a role in reducing brain oedema but preclinical studies are needed to assess their effectiveness. We evaluated the role of pretreatment with 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo(3, 4-d)pyrimidine (PP1), an Src tyrosine kinase inhibitor, in reducing cerebral oedema and preserving neurological function measured 24 hours after an automated cortical cryoinjury in mice. Sixteen adult male Swiss albino mice were subjected to an automated cortical cryoinjury using a dry ice-acetone mixture. The experimental group (n = 8) received an intraperitoneal injection of PP1 dissolved in dimethyl sulfoxide (DMSO) at a dose of 1.5 mg/kg body weight 45 minutes prior to the injury. The control group (n = 8) received an intraperitoneal injection of DMSO alone. A further eight mice underwent sham injury. The animals were evaluated using the neurological severity score (NSS) at 24 hours post-injury, after which the animals were sacrificed and their brains removed, weighed, dehydrated for 48 hours and weighed again. The percentage of brain water content was calculated as: {[(wet weight-dry weight)/wet weight] × 100}. The mean (standard deviation, SD) NSS was 11.7 (1.8) in the experimental group and 10.5 (1.3) in the control group (p = 0.15). The mean (SD) percentage water content of the brain was 78.6% (1.3%) in the experimental group and 77.2% (1.1%) in the control group (p = 0.03). The percentage water content in the experimental and control groups were both significantly higher than in the sham injury group. The immediate pre-injury administration of PP1 neither reduced cerebral oedema (water content %) nor preserved neurological function (NSS) when compared to a control group in this model of cortical cryoinjury.
机译：在神经外科实践中，脑水肿是发病的重要原因。据我们所知，目前尚无用于预防或治疗脑水肿的理想药物。基于目前对脑水肿发病机理的了解，酪氨酸激酶抑制剂可能在减轻脑水肿中起作用，但是需要临床前研究来评估其有效性。我们评估了Src酪氨酸激酶抑制剂4-氨基-5-（4-甲基苯基）-7-（叔丁基）吡唑并（3，4-d）嘧啶（PP1）的预处理在减轻脑水肿中的作用在小鼠自动皮质冰冻损伤后24小时测量保持神经功能。使用干冰-丙酮混合物对16只成年雄性瑞士白化病小鼠进行自动皮质冷冻损伤。实验组（n = 8）在受伤前45分钟接受腹膜内注射溶解于二甲亚砜（DMSO）中的PP1，剂量为1.5 mg / kg体重。对照组（n = 8）仅接受腹膜内注射DMSO。另外八只小鼠遭受了假伤。在损伤后24小时，使用神经系统严重程度评分（NSS）对动物进行评估，然后将动物处死并取出其大脑，称重，脱水48小时，然后再次称重。脑含水量的百分比计算为：{[（（干重-干重）/湿重]×100}。实验组的NSS平均值（标准差，SD）为11.7（1.8），对照组为10.5（1.3）（p = 0.15）。实验组的大脑平均含水量（SD）为78.6％（1.3％），对照组为77.2％（1.1％）（p = 0.03）。实验组和对照组的水含量百分比均显着高于假伤组。在此皮质冷冻损伤模型中，与对照组相比，PP1损伤前即刻给药既不减少脑水肿（水含量％），也不保留神经功能（NSS）。

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