Lorenzi M, Healy D P, Hawkins R, Printz J M, Printz M P
Diabetologia. 1986 Jan;29(1):58-62. doi: 10.1007/BF02427282.
Whether the increased capillary permeability characteristic of diabetes extends to the blood-brain barrier is presently unclear. We have examined in streptozotocin-diabetic rats the permeability of the blood-brain barrier at the level of 12 discrete brain regions employing 3 intravenous tracers of different molecular weight: sucrose, insulin and horseradish peroxidase. In animals killed 5 min after tracer injection both the sucrose and the inulin spaces were similar to controls. In order to assess whether more prolonged circulation of tracers would uncover leakage, we studied brain spaces at longer intervals after tracer injections. When inulin was allowed to circulate for 15 min prior to killing, animals with 4 weeks of diabetes (but not 2 weeks) exhibited larger inulin spaces at the level of the medio-basal hypothalamus (p less than 0.01), medio-dorsal hypothalamus (p less than 0.05) and periaqueductal gray (p less than 0.01). Horseradish peroxidase, even after 75 min of perfusion, remained confined in both diabetic and control animals to central nervous system areas devoid of blood-brain barrier. Thus, after a relatively short duration of diabetes the blood-brain barrier manifests an increased permeability. It is subtle, limited to some brain regions and selective for low molecular weight tracers.
目前尚不清楚糖尿病所特有的毛细血管通透性增加是否会扩展至血脑屏障。我们使用三种不同分子量的静脉示踪剂：蔗糖、胰岛素和辣根过氧化物酶，在链脲佐菌素诱导的糖尿病大鼠中，检测了12个离散脑区水平的血脑屏障通透性。在注射示踪剂后5分钟处死的动物中，蔗糖和菊粉间隙与对照组相似。为了评估示踪剂更长时间的循环是否会发现渗漏，我们在注射示踪剂后的更长时间间隔研究了脑间隙。当在处死前让菊粉循环15分钟时，患有4周糖尿病（而非2周）的动物在中基底下丘脑（p<0.01）、中背下丘脑（p<0.05）和导水管周围灰质（p<0.01）水平表现出更大的菊粉间隙。即使灌注75分钟后，辣根过氧化物酶在糖尿病动物和对照动物中仍局限于没有血脑屏障的中枢神经系统区域。因此，在糖尿病持续时间相对较短后，血脑屏障表现出通透性增加。这种增加很细微，仅限于某些脑区，并且对低分子量示踪剂具有选择性。
