Lyden P D, Jackson-Friedman C, Lonzo-Doktor L
Neurology and Research Services of the San Diego Veterans Administration Medical Center, USA.
Stroke. 1997 Feb;28(2):387-91. doi: 10.1161/01.str.28.2.387.
No therapy has been rigorously proven effective for intracerebral hematoma, although surgery is frequently used for some types of lobar hemorrhages. Since intracerebral mass causes significant ischemia in surrounding brain, we reasoned that anti-ischemia therapy might improve outcome after experimental hematoma.
We stereotaxically injected varying doses of bacterial collagenase into the caudate nucleus of rats. Four hours later we administered intravenously 2 mg/kg muscimol, a potent agonist of the gamma-aminobutyric acid-A receptor (n = 20); 1 mg/kg MK-801, an antagonist of the N-methyl-D-aspartate receptor (n = 17); or saline (n = 28). Forty-eight hours after collagenase injection we rated each animal using a standard rodent neurological examination. The ratings were compared with the amounts of injected collagenase by the quantal bioassay procedure. Brains were then prepared for histomorphometry and brain volumes estimated.
We found that the ED50 for collagenase (amount of enzyme that renders 50% of the subjects abnormal) was 0.77 +/- 0.09 U in saline-treated subjects. Treatment with muscimol significantly increased the ED50 to 1.2 +/- 0.21 U, for a potency ratio of 1.55 +/- 0.34 (t = 1.7, P < .05). MK-801 did not affect outcome. Volume of hematoma was significantly correlated with amount of injected collagenase (n = 33, r = .64, P < .001). Volumes of basal ganglia and white matter were significantly reduced by hemorrhage, and muscimol partially ameliorated this.
We conclude that muscimol significantly improves neurological outcome after intracerebral hematoma.
尽管手术常用于某些类型的脑叶出血，但尚无疗法被严格证明对脑内血肿有效。由于脑内肿块会导致周围脑组织显著缺血，我们推测抗缺血治疗可能会改善实验性血肿后的预后。
我们通过立体定向向大鼠尾状核注射不同剂量的细菌胶原酶。4小时后，静脉注射2mg/kg的蝇蕈醇（一种γ-氨基丁酸-A受体的强效激动剂，n = 20）；1mg/kg的MK-801（一种N-甲基-D-天冬氨酸受体拮抗剂，n = 17）；或生理盐水（n = 28）。胶原酶注射48小时后，使用标准的啮齿动物神经学检查对每只动物进行评分。通过定量生物测定程序将评分与注射的胶原酶量进行比较。然后制备脑组织进行组织形态计量学分析并估计脑体积。
我们发现，生理盐水处理组中胶原酶的半数有效剂量（使50%的受试对象出现异常的酶量）为0.77±0.09U。蝇蕈醇治疗使半数有效剂量显著增加至1.2±0.21U，效价比为1.55±0.34（t = 1.7，P <.05）。MK-801对预后无影响。血肿体积与注射的胶原酶量显著相关（n = 33，r =.64，P <.001）。出血使基底神经节和白质体积显著减小，蝇蕈醇可部分改善这一情况。
我们得出结论，蝇蕈醇可显著改善脑内血肿后的神经功能预后。
