Lyden P, Lonzo L, Nunez S
Department of Neurosciences, UCSD School of Medicine, Veterans Administration Medical Center, California, USA.
J Neurotrauma. 1995 Apr;12(2):223-30. doi: 10.1089/neu.1995.12.223.
We sought to extend the therapeutic window for acute stroke therapy using the combination of a glutamate antagonist and a GABA agonist, which in prior studies was effective if given 5 min after stroke. We used a quantal bioassay to measure neuroprotective potency after injection of several thousand microspheres into the cerebral circulation of rats. The GABA-A agonist muscimol, but not MK-801, was effective if given 30, 45, or 60 min after embolization (potency ratio compared with saline of 3.0, 2.3, 1.8, respectively). If muscimol was combined with MK-801 at lower doses of each drug, the combination was neuroprotective (potency ratio of 4.2). Agonists of GABA-A, but not GABA-B, receptors blocked the toxic vacuolization seen in the cingulate and retrosplenial cortex after MK-801 treatment. Combination chemotherapy appears to extend the time window for acute stroke therapy in rats to 1 h and to result in fewer side effects.
我们试图通过联合使用谷氨酸拮抗剂和γ-氨基丁酸（GABA）激动剂来延长急性中风治疗的治疗窗口，在先前的研究中，如果在中风后5分钟给药，这种联合用药是有效的。我们使用定量生物测定法，在向大鼠脑循环中注射数千个微球后测量神经保护效力。栓塞后30、45或60分钟给予GABA-A激动剂蝇蕈醇有效，但给予MK-801无效（与生理盐水相比，效力比分别为3.0、2.3、1.8）。如果蝇蕈醇与较低剂量的MK-801联合使用，该联合用药具有神经保护作用（效力比为4.2）。GABA-A受体激动剂而非GABA-B受体激动剂可阻断MK-801治疗后扣带回和压后皮质出现的毒性空泡化。联合化疗似乎可将大鼠急性中风治疗的时间窗口延长至1小时，并减少副作用。
