Kano T, Katayama Y, Kawamata T, Hirota H, Tsubokawa T
Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan.
Brain Res. 1994 Mar 28;641(1):149-54. doi: 10.1016/0006-8993(94)91829-5.
Systemic administration of propentofylline (PPF), an adenosine uptake inhibitor, has been demonstrated to protect CA1 pyramidal cells from death following transient cerebral ischemia in gerbils. In order to examine the direct effects of this inhibitor, we tested whether or not PPF administered into the hippocampus in situ through a microdialysis probe could attenuate ischemia-induced excitatory amino acid (EAA) release and prevent subsequent death of CA1 pyramidal cells in the gerbil. The EAA release and death of CA1 pyramidal cells observed in the hippocampus were compared with those in the contralateral hippocampus of the same animal into which vehicle alone was administered. The results indicated that pre- as well as post-treatments with PPF inhibited the death of CA1 pyramidal cells after 5-min ischemia in a dose-dependent manner, but did not significantly alter the EAA release during ischemia and reperfusion in the same animals. While the neuroprotective effect of PPF against ischemic damage has commonly been ascribed to attenuation of EAA release during ischemia, other actions of adenosine such as those influencing the synaptic responses, neuronal excitation, and local cerebral circulation, or as yet unidentified actions may be involved in the observed neuroprotective effects of PPF.
已证明，腺苷摄取抑制剂丙戊茶碱（PPF）的全身给药可保护沙土鼠短暂性脑缺血后CA1锥体细胞免于死亡。为了研究这种抑制剂的直接作用，我们通过微透析探针原位向海马内注射PPF，测试其是否能减轻缺血诱导的兴奋性氨基酸（EAA）释放，并预防沙土鼠CA1锥体细胞随后的死亡。将海马中观察到的CA1锥体细胞的EAA释放和死亡情况与同一动物对侧海马（仅注射赋形剂）中的情况进行比较。结果表明，PPF预处理和后处理均以剂量依赖的方式抑制了5分钟缺血后CA1锥体细胞的死亡，但对同一动物缺血和再灌注期间的EAA释放没有显著影响。虽然PPF对缺血性损伤的神经保护作用通常归因于缺血期间EAA释放的减弱，但腺苷影响突触反应、神经元兴奋和局部脑循环等其他作用，或尚未明确的作用，可能参与了所观察到的PPF的神经保护作用。
