Department of Neurological Sciences, Christian Medical College, Vellore 632 004, India.
J Clin Neurosci. 2013 Apr;20(4):593-6. doi: 10.1016/j.jocn.2012.06.009. Epub 2013 Feb 26.
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 24hours 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 1.5mg/kg body weight 45minutes 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 24hours post-injury, after which the animals were sacrificed and their brains removed, weighed, dehydrated for 48hours 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.
脑水肿是神经外科学实践中发病率的一个重要原因。据我们所知，目前尚无预防或治疗脑水肿的理想药物。基于对脑水肿发病机制的现有认识，酪氨酸激酶抑制剂在减轻脑水肿方面可能具有作用，但需要进行临床前研究来评估其疗效。我们评估了在小鼠大脑皮质冷冻损伤前预处理 4-氨基-5-(4-甲基苯基)-7-(叔丁基)吡唑并[3,4-d]嘧啶（PP1）的作用，PP1 是一种Src 酪氨酸激酶抑制剂，以减少脑水肿并保留 24 小时后神经功能的作用。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）在损伤前 45 分钟接受腹腔注射溶解在二甲基亚砜（DMSO）中的 PP1，剂量为 1.5mg/kg 体重。对照组（n=8）接受腹腔注射 DMSO 单独。另外 8 只小鼠进行假损伤。在损伤后 24 小时，使用神经严重程度评分（NSS）评估动物，之后处死动物并取出其大脑，称重，脱水 48 小时后再次称重。脑水含量的百分比计算为：{[(湿重-干重)/湿重]×100}。实验组的平均（标准差，SD）NSS 为 11.7（1.8），对照组为 10.5（1.3）（p=0.15）。实验组脑水含量的平均（SD）为 78.6%（1.3%），对照组为 77.2%（1.1%）（p=0.03）。实验组和对照组的脑水含量百分比均明显高于假损伤组。在这种皮质冷冻损伤模型中，与对照组相比，PP1 的即刻损伤前给药既不能减轻脑水肿（水含量%），也不能保存神经功能（NSS）。
