Perry V L, Young R S, Aquila W J, During M J
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06510.
Pediatr Res. 1993 Aug;34(2):187-91. doi: 10.1203/00006450-199308000-00017.
Excessive extracellular fluid concentrations of the amino acids glutamate and aspartate play an important role in the pathogenesis of neuronal cell damage during hypoxia, hypoglycemia, and seizure. The purpose of these investigations was to test the hypothesis that bacterial meningitis causes progressive increase in excessive extracellular fluid concentrations of excitatory and inhibitory neurotransmitters. To test this hypothesis, Escherichia coli was injected intracisternally in juvenile rabbits after which neurotransmitter concentrations were measured with in vivo microdialysis. The data showed significant elevation of the excitatory amino acids aspartate and glutamate, as well as of the inhibitory neurotransmitters gamma-amino butyric acid and taurine in the excessive extracellular fluid of animals injected with E. coli compared with control animals injected with saline. However, concentrations of these excitatory and inhibitory amino acids rose late in the course of meningitis, at a time when the animals were hypotensive (mean blood pressure < or = 40 mm Hg). These data show that the major increase in excitatory neurotransmitters during experimental meningitis occurs in association with the cerebral ischemia produced by septic shock rather than being produced by the meningitis itself.
细胞外液中谷氨酸和天冬氨酸的浓度过高，在缺氧、低血糖和癫痫发作时神经元细胞损伤的发病机制中起重要作用。这些研究的目的是检验细菌性脑膜炎会导致细胞外液中兴奋性和抑制性神经递质浓度逐渐升高这一假说。为了验证这一假说，将大肠杆菌注入幼年兔的脑池中，然后用体内微透析法测量神经递质浓度。数据显示，与注射生理盐水的对照动物相比，注射大肠杆菌的动物细胞外液中兴奋性氨基酸天冬氨酸和谷氨酸以及抑制性神经递质γ-氨基丁酸和牛磺酸的浓度显著升高。然而，这些兴奋性和抑制性氨基酸的浓度在脑膜炎病程后期升高，此时动物处于低血压状态（平均血压≤40mmHg）。这些数据表明，实验性脑膜炎期间兴奋性神经递质的主要增加与感染性休克引起的脑缺血有关，而非脑膜炎本身所致。
