Gavazzi I, Boyle K S, Cowen T
Department of Anatomy and Developmental Biology, Royal Free Hospital School of Medicine, London, UK.
Brain Res. 1996 Sep 23;734(1-2):167-74.
We have investigated the contribution of the acellular component (i.e., the extracellular matrix, or ECM) in determining the innervation density of peripheral target tissue, and the possible involvement of ECM molecules in age-related axonal atrophy. We addressed this issue using cerebral blood vessels where both the overall density and the density of sympathetic innervation decrease by 50% in aged rats. In order to study the capacity of the ECM to influence pattern and density of innervation, cerebral blood vessels from young (6 weeks) and old (24 months) rats were repeatedly freeze-thawed to kill the cellular component of the vessel wall before transplantation in oculo into young host rats. After 4 weeks, the nature and degree of reinnervation of transplants by host nerves was studied by quantitative immunohistochemistry using PGP9.5 (a general neuronal marker) or CGRP (calcitonin gene-related peptide, a sensory marker), or catecholamine histochemistry using the glyoxylic acid technique to visualise noradrenergic sympathetic nerves. The density of reinnervation was measured by computerized image analysis. The PGP-immunoreactive reinnervation on old transplanted cerebral blood vessels was significantly less dense compared to young ones. However, nerve density on both young and old transplants was lower than on control, ex vivo blood vessels. CGRP-positive nerves on both young and old transplants were sparse, but similar to control tissues, whereas catecholamine-containing nerves were very sparse on all transplants, and significantly less than on control blood vessels. These results suggest that alterations occur in the aged ECM, that make it less receptive to innervation. However, they also indicate that, along with the ECM, factors produced by the cellular components of the blood vessel wall are essential, at least for the maintenance of the sympathetic innervation.
我们研究了无细胞成分（即细胞外基质，或ECM）在决定外周靶组织神经支配密度方面的作用，以及ECM分子在与年龄相关的轴突萎缩中可能的参与情况。我们利用脑血 vessels 来解决这个问题，在老年大鼠中，脑血 vessels 的总体密度和交感神经支配密度均下降了50%。为了研究ECM影响神经支配模式和密度的能力，将年轻（6周）和老年（24个月）大鼠的脑血 vessels 反复冻融以杀死血管壁的细胞成分，然后在眼内移植到年轻的宿主大鼠中。4周后，通过使用PGP9.5（一种通用的神经元标记物）或CGRP（降钙素基因相关肽，一种感觉标记物）的定量免疫组织化学，或使用乙醛酸技术进行儿茶酚胺组织化学以可视化去甲肾上腺素能交感神经，研究宿主神经对移植组织的再支配性质和程度。通过计算机图像分析测量再支配密度。与年轻的移植脑血 vessels 相比，老年移植脑血 vessels 上的PGP免疫反应性再支配密度明显较低。然而，年轻和老年移植组织上的神经密度均低于对照的离体血管。年轻和老年移植组织上的CGRP阳性神经都很稀疏，但与对照组织相似，而所有移植组织上含儿茶酚胺的神经都非常稀疏，且明显少于对照血管。这些结果表明，老年ECM发生了改变，使其对神经支配的接受性降低。然而，它们也表明，与ECM一起，血管壁细胞成分产生的因子至少对于交感神经支配的维持是必不可少的。
