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去传入诱导的大鼠背角改变:II. 外周神经中枢突经链霉蛋白酶选择性中毒的影响

Deafferentation-induced alterations in the rat dorsal horn: II. Effects of selective poisoning by pronase of the central processes of a peripheral nerve.

作者信息

LaMotte C C, Kapadia S E

机构信息

Section of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06510.

出版信息

J Comp Neurol. 1987 Dec 8;266(2):198-208. doi: 10.1002/cne.902660206.

Abstract

Studies of deafferentation and regeneration, as well as studies requiring several tracing techniques, would benefit from availability of a substance that would selectively lesion the central components of a single peripheral nerve. Pronase, a combination of proteolytic enzymes, was tested for this purpose. Three weeks following microinjection of Pronase (5-25 mg) into the rat sciatic nerve, many ganglia cells in the L3-L5 ganglia were degenerated. Degeneration of primary afferents also was evident in the dorsal horn, as detected by silver Fink-Heimer methods. Patterns of terminal fields coincided with those mapped in normal rats for the sciatic nerve by using HRP transport. Ultrastructural changes were similar to those seen at 3 weeks following sciatic nerve section or rhizotomy, as described in our companion paper. However, degenerative changes following Pronase injection of the sciatic nerve were quantitatively greater than those following sciatic nerve section alone. Degenerating terminals were either electron lucent and swollen, electron dense, or filamentous with loss of vesicles. Postsynaptic dendrites, and occasionally somata, also showed signs of degeneration. Some became electron dense, others accumulated osmiophilic floccular material, but most became electron lucent and developed large membrane-bound cavities. Glial processes expanded around degenerating elements, wrapping around both terminals and dendrites. Glial sheets covered denervated dendritic and somatic spines, separating them from their terminals. Labyrinth formations of glial sheaths around debris were also found. Pronase appears to mimic the effects of mechanical destruction of primary afferents, but when compared to rhizotomy, is selective for the afferents of a single nerve, and, when compared to nerve section, produces a greater effect. Further, the substance is relatively safe for investigators compared to other toxins such as ricin.

摘要

去传入神经和再生的研究,以及需要多种示踪技术的研究,将受益于一种能够选择性损伤单一外周神经中枢成分的物质。为此,对一种蛋白水解酶组合——链霉蛋白酶进行了测试。在将链霉蛋白酶(5 - 25毫克)微量注射到大鼠坐骨神经三周后,L3 - L5神经节中的许多神经节细胞发生了退化。如通过银芬克 - 海默方法检测到的,初级传入神经在背角的退化也很明显。终末场的模式与通过使用辣根过氧化物酶运输在正常大鼠中绘制的坐骨神经模式一致。超微结构变化与我们的配套论文中描述的坐骨神经切断或神经根切断后3周时所见的变化相似。然而,注射链霉蛋白酶后坐骨神经的退化性变化在数量上比单独坐骨神经切断后的变化更大。退化的终末要么电子透明且肿胀,要么电子致密,要么呈丝状且囊泡丢失。突触后树突,偶尔还有胞体,也显示出退化的迹象。一些变得电子致密,另一些积累嗜锇性絮状物质,但大多数变得电子透明并形成大的膜结合腔。神经胶质突起在退化的成分周围扩张,包裹着终末和树突。神经胶质片覆盖去神经支配的树突和体细胞棘,将它们与其终末分开。还发现了围绕碎片的神经胶质鞘迷宫状结构。链霉蛋白酶似乎模拟了初级传入神经机械破坏的效果,但与神经根切断相比,它对单一神经的传入神经具有选择性,与神经切断相比,产生的效果更大。此外,与蓖麻毒素等其他毒素相比,该物质对研究人员相对安全。

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