Lee M, Sakatani K, Young W
Department of Neurosurgery, New York University Medical Center, NY 10016.
Brain Res. 1993 Jan 22;601(1-2):14-9. doi: 10.1016/0006-8993(93)91690-t.
GABA (gamma-aminobutyric acid) depresses axonal conduction in neonatal dorsal columns. GABA released by injured spinal neurons may diffuse to white matter and contribute to secondary axonal damage. We studied the effects of hypoxia and GABAA receptor blockade on dorsal column conduction in vitro. The experiments compared the effects of hypoxia on longitudinally hemisected spinal cords and isolated neonatal dorsal columns. Before hypoxia, electrical stimulation elicited robust conducted compound action potentials in both isolated dorsal columns and hemicords. The tissues were superfused for 120 min with a hypoxic Ringer's solution saturated with 95% N2 and 5% CO2, followed by oxygenated Ringer's solution for 90 min. Isolated dorsal columns were remarkably insensitive to hypoxia. Response amplitudes fell by only 11 +/- 7% (n = 5) during hypoxia. In hemicords, however, hypoxia reduced response amplitudes by 56 +/- 16% (n = 5, mean +/- S.E.M.) and re-oxygenation did not restore response amplitude. We applied bicucullin (10(-5) M) to block GABAA receptors in the hemicords during hypoxia. Response amplitudes in bicucullin-treated hemicords fell by only 3 +/- 9% (n = 5) during hypoxia but declined 31 +/- 5% during re-oxygenation. These results suggest that endogenous GABA released from gray matter contributes to hypoxia-induced dorsal-column conduction failure.
γ-氨基丁酸(GABA)可抑制新生动物背柱的轴突传导。受损脊髓神经元释放的GABA可能扩散至白质并导致继发性轴突损伤。我们在体外研究了缺氧和GABAA受体阻断对背柱传导的影响。实验比较了缺氧对纵向半切脊髓和分离的新生动物背柱的影响。在缺氧前,电刺激在分离的背柱和半切脊髓中均引发了强劲的复合动作电位传导。用含95% N2和5% CO2的缺氧林格氏液对组织进行120分钟的灌流,随后用充氧林格氏液灌流90分钟。分离的背柱对缺氧明显不敏感。缺氧期间反应幅度仅下降11±7%(n = 5)。然而,在半切脊髓中,缺氧使反应幅度降低了56±16%(n = 5,平均值±标准误),而复氧并未恢复反应幅度。在缺氧期间,我们应用荷包牡丹碱(10⁻⁵ M)阻断半切脊髓中的GABAA受体。在缺氧期间,经荷包牡丹碱处理的半切脊髓的反应幅度仅下降3±9%(n = 5),但在复氧期间下降了31±5%。这些结果表明,从灰质释放的内源性GABA导致了缺氧诱导的背柱传导障碍。