Urban L, Neill K H, Crain B J, Nadler J V, Somjen G G
Department of Cell Biology, Duke Medical Center, Durham, NC 27710.
Adv Exp Med Biol. 1990;268:491-500. doi: 10.1007/978-1-4684-5769-8_54.
Selective delayed post-ischemic degeneration of CA1b neurons takes place in tissue slices in vitro as it does in brain in situ. Therefore neither selectivity nor the delay of the process can be explained by vascular factors. Changes of orthodromic evoked potentials precede morphologic signs of degeneration, but antidromic activation of neurons fails pari passu with histopathologic degeneration. The marked, transient, enhancement of excitatory synaptic potentials is compatible with the idea that increased release of excitatory amino acids contributes to neuron damage. The fact that degeneration proceeds in the absence of spontaneous activity or overt electrographic seizures indicates, however, that increased excitation cannot be the sole cause of the damage. Postsynaptic excitability of neurons decreases even while synaptic potentials are enhanced. The mechanism of decreased excitability is not clear, but its development could be interpreted as a compensatory change, counteracting enhanced excitatory transmission. We confirmed that it is possible to save neurons by drug treatment administered after the ischemic insult, and demonstrated that such protection is not due to an effect on blood vessels. These findings are relevant to the proposed clinical use of NMDA receptor antagonists to prevent ischemic brain damage (Meldrum, 1985; Rothman and Olney, 1986; Choi, 1988).
CA1b神经元选择性延迟性缺血后变性在体外组织切片中发生的情况与在原位脑内一样。因此，该过程的选择性和延迟都不能用血管因素来解释。顺向诱发电位的变化先于变性的形态学迹象，但神经元的逆向激活与组织病理学变性同步消失。兴奋性突触电位的显著、短暂增强与兴奋性氨基酸释放增加导致神经元损伤的观点相符。然而，变性在无自发活动或明显脑电图癫痫发作的情况下仍会发生，这表明兴奋性增加并非损伤的唯一原因。即使突触电位增强，神经元的突触后兴奋性仍会降低。兴奋性降低的机制尚不清楚，但其发展可被解释为一种代偿性变化，以抵消增强的兴奋性传递。我们证实，在缺血性损伤后给予药物治疗有可能挽救神经元，并证明这种保护作用并非源于对血管的影响。这些发现与NMDA受体拮抗剂用于预防缺血性脑损伤的临床应用提议相关（梅尔德伦，1985；罗斯曼和奥尔尼，1986；崔，1988）。
