Extracellular matrix molecules influence innervation density in rat cerebral blood vessels

Abstract

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.

Increased Fibronectin Expression in Sturge-Weber Syndrome Fibroblasts and Brain Tissue

“…Furthermore, fibronectin has been shown to have potent effects on sympathetic nerve outgrowth and vessel innervation (26,27). Cunha e Sa et al (28) demonstrated that malformed cortical vessels in SWS are innervated only by noradrenergic sympathetic nerve fibers.…”

Reduced sympathetic neurite outgrowth on uterine tissue sections from rats treated with estrogen

“…These results mimic the inhibitory effects elicited by estrogen both in immature and in adult uterine sympathetic nerves in vivo and suggest that substrate-associated signals contribute to the selective denervation elicited by estrogen in the myometrium. Similarly, anterior eye chamber transplantation studies involving tissues submitted to freeze-thaw cycles before transplantation have shown that poorly innervated cerebral blood vessels from aged rats attract fewer reinnervating nerve fibers from the iris than the normally innervated tissues from young animals (Gavazzi et al 1996). A reduced neuritic growth occurring on sections of estrogenized myometrium is observed, in spite of the fact that the sympathetic neurons used in this study do not normally innervate the uterus (Vera et al 1997;Houdeau et al 1998).…”

Effect of Aging on Recovery of Cutaneous Nociception After End-to-Side Nerve Repair in the Rat

“…However, age-dependent reduction in laminin content impaired the sensory innervation of rat cerebral vessels. 43,44 Furthermore, the lack of age-related difference in sprouting of the unmyelinated fibers found in this study is pointing to the existence of relevant biologic differences between unmyelinated and myelinated SC populations. 45 Namely, it is possible that aging negatively affects SCs of myelinated fibers and not the SCs of unmyelinated fibers.…”