BLOOD-BRAIN BARRIER OPENING TO HORSERADISH PEROXIDASE AT ONSET OF BICUCULLINE

荷包牡丹碱起效时血脑屏障对辣根过氧化物酶开放

• 批准号: 4696991
• 负责人: C NATSCH
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4696991
• 关键词: active transport; arterioles; blood brain barrier; capillary; epilepsy; fluorescent dye /probe; macromolecule; neurotransmitters; peroxidases; synapses; vascular endothelium permeability

Rabbits which had received horseradish peroxidase (HRP) intravenously were subjected to bicuculline-induced generalized seizures of 15 min duration in order to elucidate the mechanism by which macromolecules traverse the blood- brain barrier (BBB) in specific neuroanatomically defined brain areas. As a rule, transendothelial pinocytosis at the level of arterioles was the main route of passage. In addition, tracer-filled pinocytotic vesicles were also observed in the capillaries of the hippocampus, thalamus, whereas in thalamus, hypothalamus and septum, they were present also in the endothelium of venules. Indication of an opening of the interendothelial tight junctions was found in the hypothalamus. The HRP, which had reached the neuropil due to the seizure-evoked BBB opening, accumulated in the interstitial spaces and penetrated the synaptic cleft region. Uptake of the tracer in vesicular form into presynaptic boutons, presumably excitatory ones, was observed in all brain regions; it was frequent in pallidum, hippocampus and medulla oblongata and very intense in the thalamus. Concomitant uptake in postsynaptic dendrites, was present mostly in the vicinity of boutons. Incorporation into glial processes was rare. It is concluded that blood-borne macromolecules traverse the BBB by regionally selective, transmitter-controlled pinocytotic transport and the the neuronal uptake of the foreign protein during the generalized seizures is at least partially dependent on the involvement of synapses of particular brain regions. These studies contribute to the understanding of mechanisms operative in epileptic seizures.

静脉注射辣根过氧化物酶（HRP）的家兔， 进行荷包牡丹碱诱导的全身性癫痫发作15分钟， 为了阐明大分子穿过血液的机制， 脑屏障（BBB）在特定的神经解剖学定义的脑区。 作为 一个规则，在小动脉水平的跨内皮细胞胞饮是 主要通道。 此外，充满示踪剂的胞饮小泡 在海马体、丘脑的毛细血管中也观察到， 在丘脑、下丘脑和隔区， 微静脉内皮 内皮间开口的指示 在下丘脑中发现紧密连接。 HRP在脑缺血诱发的血脑屏障中到达神经元， 开放，积累在间隙空间，并穿透突触 裂区 囊泡形式的示踪剂进入突触前 在所有的大脑区域都观察到了扣结，可能是兴奋性的，它 常见于苍白球、海马和延髓， 在丘脑中很强烈 突触后树突的伴随摄取， 主要存在于钮扣附近。 掺入胶质细胞 过程是罕见的。 得出结论，血液传播的大分子通过 区域选择性的，递质控制的胞饮转运， 在全身性癫痫发作期间神经元对外源蛋白的摄取 至少部分依赖于突触的参与， 特定的大脑区域。 这些研究有助于理解 癫痫发作的机制