Lundgren J, Smith M L, Mans A M, Siesjö B K
Department of Neurobiology, University of Lund, Sweden.
Stroke. 1992 May;23(5):719-24. doi: 10.1161/01.str.23.5.719.
Treatment with the ketone body precursor 1,3-butanediol has been suggested to ameliorate hypoxic/ischemic brain damage. Butanediol could provide an alternative energy substrate for the brain, thereby decreasing the amount of glycolytically produced lactate. Hyperglycemia aggravates brain damage after brain ischemia and causes fatal postischemic seizures, probably by increasing the production of lactate and decreasing the pH. We studied whether butanediol treatment altered the adverse consequences following ischemia complicated by hyperglycemia.
Hyperglycemic adult male rats were given 25 or 50 mmol.kg-1 body wt butanediol intravenously 30 minutes before 10 minutes of transient forebrain ischemia. Morphological evaluation was performed following perfusion-fixation after 15 hours of recovery. Blood concentrations of beta-hydroxybutyrate, acetoacetate, glucose, and lactate and brain tissue concentrations of energy metabolites were measured before and after ischemia.
Blood levels of ketone bodies increased in the butanediol-treated rats. Ischemia decreased the blood levels of acetoacetate but increased the levels of beta-hydroxybutyrate by a similar amount, resulting in unchanged high levels of total ketone bodies in the animals that received butanediol. Brain tissue levels of glucose, energy metabolites, and lactate showed no difference between butanediol- and saline-treated rats. Furthermore, compared with saline-treated animals butanediol-treated rats showed no decrease in brain damage and no attenuation in the development of postischemic seizures.
The ketone body precursor 1,3-butanediol offers no protective effect in transient forebrain ischemia complicated by hyperglycemia.
有人提出用酮体前体1,3 - 丁二醇进行治疗可改善缺氧/缺血性脑损伤。丁二醇可为大脑提供替代能量底物，从而减少糖酵解产生的乳酸量。高血糖会加重脑缺血后的脑损伤，并引发致命的缺血后癫痫发作，可能是通过增加乳酸生成和降低pH值来实现的。我们研究了丁二醇治疗是否能改变缺血合并高血糖后的不良后果。
在成年雄性高血糖大鼠短暂性前脑缺血10分钟前30分钟，静脉给予25或50 mmol·kg-1体重的丁二醇。恢复15小时后进行灌注固定，然后进行形态学评估。在缺血前后分别测量血液中β-羟基丁酸、乙酰乙酸、葡萄糖和乳酸的浓度以及脑组织中能量代谢物的浓度。
丁二醇治疗组大鼠血液中酮体水平升高。缺血使乙酰乙酸的血液水平降低，但β-羟基丁酸水平升高了类似的量，导致接受丁二醇治疗的动物体内总酮体水平保持不变。丁二醇治疗组和生理盐水治疗组大鼠的脑组织葡萄糖、能量代谢物和乳酸水平没有差异。此外，与生理盐水治疗组动物相比，丁二醇治疗组大鼠的脑损伤没有减轻，缺血后癫痫发作的发展也没有得到缓解。
酮体前体1,3 - 丁二醇对合并高血糖的短暂性前脑缺血没有保护作用。
