During stroke, interruption of blood flow and nutrients to brain cells causes them to die because they no longer receive oxygen and nutrients. By examining the milieu around neurons that have become hypoxic (short of oxygen), Michio Tamatani and colleagues at Osaka University, Japan, discovered a new polypeptide that could be exploited to become a treatment for stroke (Nature Medicine, Vol. 7, No.3, 01 Mar 2001).
They isolated a 150 kD oxygen-regulated protein (ORP150) and showed that in the brains of people that had died of stroke, this molecule was expressed at low levels in neurons, but at high levels in brain cells called astrocytes. Similarly, in vitro ORP150 appears to protect astrocytes from damage, whereas neurons that do not express large quantities of this peptide suffer greater damage. Transgenic mice that overexpress ORP150 suffered less neuronal damage in a model of stroke than controls.
The scientists write, "upregulation of ORP150 under [hypoxic] conditions may represent a novel therapeutic target to enhance cell survival."
In a separate paper, researchers at Lund University in Sweden have isolated another protein that may protect against stroke and possibly against damage to tissue during heart attack.
Reinhard Fässler and colleagues examined the properties of a protein called fibronectin that is present both inside cells and in the plasma. Plasma fibronectin interacts with clotting agents to heal wounds to the skin and is also found in the area of ischemic brain damage. Much to their surprise, the scientists found that when they created transgenic mice lacking plasma fibronectin, would healing was not affected, but the animals suffered greater brain damage in a model of stroke than did normal mice, suggesting that fibronectin is protective in stroke.
In an accompanying News & Views article, Deane Mosher from the University of Wisconsin, writes that the study opens up new avenues of investigation such as the role of fibronectin in heart attack and ischemic damage to other organs.
Dr. Reinhard Fässler
Department of Experimental Pathology
Tel: 46 46 173400
Fax: 46 46 158202
Dr. Michio Tamatani
Department of Anatomy and Neuroscience
Graduate School of Medicine
Osaka University, Osaka
Dr Deane Mosher
Department of Medicine
University of Wisconsin
Tel: +1 608 262 1576
Fax: +1 608 263 4969
(C) Nature Medicine press release.
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