Role of endothelin-1 in astrocyte responses after acute brain damage

Abstract

We examined the possibility of the involvement of endothelin (ET)‐1, a potent vasoactive peptide, in the process of astrocyte proliferation after brain injury. Acute brain damage in rats was induced by cold‐injury. Astrocytes changed from a differentiated state to an immature, RC‐1‐positive state immediately after the injury. In the injured site, the level of ET‐1‐like immunoreactivity in the tissue was significantly increased on the first postoperative day and was sustained at a high level for 5 days. ETB receptor mRNA was markedly but transiently down‐regulated only on the first day after the injury. Brain extracts (BE) were prepared from the injured tissues, and their effects on the proliferative characteristics of astrocytes were examined in primary culture of astrocytes. The flat morphology, which was observed in association with cell proliferation, and DNA synthesis of astrocytes were enhanced by treatment with each of the BE from 1 (D1‐BE), 3 and 5 days after the injury. A monoclonal antibody that recognizes the C‐terminus of rat ET‐1 and ET‐3 inhibited the DNA synthesis of astrocytes induced by D1‐BE. These results provide experimental evidence that ET‐1 may participate in the initiation of gliosis in the acute phase of brain damage. J. Neurosci. Res. 47:590–602, 1997. © 1997 Wiley‐Liss, Inc.

CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure

“…Degeneration of severed axon tracts appears to lead to gliosis, even in regions remote from the site of trauma in the brain or spinal cord (Barrett et al, 1981;Fitch and Silver, 1997a;Massey, et al, 2006;Murray et al, 1990;Steward and Trimmer, 1997). Cytokines or other molecules that may trigger gliosis include TNF-alpha (Rostworowski et al, 1997), endothelin-1 (Hama et al, 1997), IL-1 (Giulian and Lachman, 1985), IL-6 (Chiang et al, 1994), thrombin (Nishino et al, 1993), and CNTF (Kahn et al, 1995). Some of these may originate as soluble serum factors, or they can be directly produced by astrocytes, activated microglia, or peripheral macrophages.…”

Genomic Expression Systems on Hierarchy and Network Leading to Hypertension: Long on History, Short on Facts.

“…In order to examine the role of angiotensinogen in astrocytes, we investigated a possible functional contribution of angiotensinogen or one of its angiotensin metabolites to blood-brain barrier reconstitution (54). For this purpose, we applied the cold injury model, which is a suitable experimental brain injury for evaluating the function of astrocytes (55,56). In this experiment, the interaction between astrocytes and endothelial cells is transiently disrupted by the cold injury, resulting in the leakage of small molecular weight substances, for example Evans blue dye, into the brain.…”

Connexin43 is involved in the effect of endothelin‐1 on astrocyte proliferation and glucose uptake

“…Subsequently, the ET peptides were found to have multiple and very different biological activities in both vascular and nonvascular tissues, including the central nervous system (CNS) (Masaki et al, 1992). Thus, ET-1 is present in brain endothelial cells (Yoshimoto et al, 1990), neurons (Fuxe et al, 1991), and astrocytes (MacCumber et al, 1990), and its secretion increases in several pathologies, such as cerebral ischemia (Yamashita et al, 2000), Alzheimer disease (Zhang et al, 1994), HIV infection (Chauhan et al, 2007;Didier et al, 2002), reactive gliosis (Hama et al, 1997;MacCumber et al, 1990;Nie and Olsson, 1996), and astrocytic tumors (Stiles et al, 1997). Astrocytes express all components of the ET system, including G-protein-coupled ET receptors (Ehrenreich et al, 1999) and ET-1 therefore behaves as a growth factor, exerting important biological effects, such as the induction of proliferation (Gadea et al, 2008;Supattapone et al, 1989;Tabernero et al, 2001;Teixeira et al, 2000), the increase in the rate of glucose uptake (Tabernero et al, 1996a;Tabernero et al, 2001), or changes in protein content and morphology (Hasselblatt et al, 2003).…”