Lyeth B G, Gong Q Z, Dhillon H S, Prasad M R
Division of Neurosurgery, Department of Surgery, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0693, USA.
Brain Res. 1996 Dec 2;742(1-2):63-70. doi: 10.1016/s0006-8993(96)01002-5.
Hippocampal levels of fatty acids extracted from phosphatidylinositol 4,5-bisphosphate (PIP2), free fatty acids (FFA), and lactate were measured after central fluid percussion traumatic brain injury (TBI) in rats. At 5 min after injury, there was a decrease in fatty acids extracted from PIP2 suggesting a decrease in PIP2. At the same time point, total FFA increased in saline-treated TBI rats. Levels of arachidonic acid were significantly decreased in PIP2, while at the same time arachidonic and stearic acids increased in FFA in saline-treated TBI rats. No significant alterations in PIP2-derived fatty acids or FFA were observed at 20 min after TBI. Hippocampal concentrations of lactate were significantly elevated at 5 and 20 min after injury in saline-treated rats. In general, these alterations were blunted by preinjury administration of the muscarinic antagonist, scopolamine. These results suggest that the PIP2 signal transduction pathway is activated in the hippocampus at the onset of central fluid percussion TBI and that the enhanced phospholipase C-catalyzed phosphodiestric breakdown of PIP2 is a major mechanism of liberation of FFA in these sites immediately after such injury. The blunting of PIP2 and FFA alterations in animals treated with scopolamine suggests that activation of muscarinic receptors significantly contributes to the phospholipase C (PLC) signal transduction pathophysiology in TBI. The attenuation of lactate accumulation in scopolamine-treated rats suggests that TBI-induced muscarinic receptor activation also contributes to increased glycolytic metabolism and/or ionic imbalances.
在大鼠中枢流体冲击性创伤性脑损伤（TBI）后，测量了从磷脂酰肌醇4,5-二磷酸（PIP2）中提取的脂肪酸、游离脂肪酸（FFA）和乳酸在海马中的水平。损伤后5分钟，从PIP2中提取的脂肪酸减少，提示PIP2减少。在同一时间点，生理盐水处理的TBI大鼠中总FFA增加。PIP2中花生四烯酸水平显著降低，而在生理盐水处理的TBI大鼠中，FFA中的花生四烯酸和硬脂酸同时增加。TBI后20分钟，未观察到PIP2衍生脂肪酸或FFA有显著变化。生理盐水处理的大鼠在损伤后5分钟和20分钟时，海马中的乳酸浓度显著升高。一般来说，这些变化在损伤前给予毒蕈碱拮抗剂东莨菪碱后会减弱。这些结果表明，在中枢流体冲击性TBI发作时，海马中的PIP2信号转导通路被激活，并且PIP2经磷脂酶C催化的磷酸二酯分解增强是此类损伤后这些部位FFA释放的主要机制。东莨菪碱处理的动物中PIP2和FFA变化的减弱表明，毒蕈碱受体的激活显著促成了TBI中的磷脂酶C（PLC）信号转导病理生理学。东莨菪碱处理的大鼠中乳酸积累的减弱表明，TBI诱导的毒蕈碱受体激活也促成了糖酵解代谢增加和/或离子失衡。
