Editors' ChoiceStroke

Protection from Hemoglobin's Dark Side

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Science Translational Medicine  16 Dec 2009:
Vol. 1, Issue 11, pp. 11ec39
DOI: 10.1126/scitranslmed.3000708

A cut on the finger or foot is unpleasant but not as dangerous as a bleeding stroke in the brain. Our body can effectively stop bleeding and heal cuts in the skin, but blood leaking into the brain can cause lasting damage. Why the difference? The culprit is hemoglobin, the red, iron-containing protein that carries oxygen to our tissues. Hemoglobin and its degradation products heme and iron are neurotoxins, and when hemoglobin leaks out of blood vessels it damages brain cells and their contents through oxidative stress and the activation of destructive enzymes. New work by Zhao et al. finds that glial cells make a protective protein called haptoglobin, which was previously thought to be absent from the brain. The safeguarding function of this protein could potentially be harnessed to help stop brain damage caused by bleeding strokes.

Haptoglobin is blood protein that binds hemoglobin that escapes from red blood cells during injury, rendering the hemoglobin harmless and allowing excretion. Haptoglobin is mainly made in the liver, and people with inflammatory conditions have high blood concentrations. The authors of the new study show that in rodents, a brain cell—the oligodendrocyte—also makes haptoglobin. Further, when the authors increased the amount of haptoglobin with a drug called sulforaphane, brain cells were protected against damage caused by lysed whole blood. Consistent with that result was the neuroprotection against damage caused by a simulated stroke that they saw in mice that overexpressed haptoglobin and the exacerbation of this kind of brain damage in mice in which haptoglobin was knocked out (deleted).

There are few ways to treat bleeding strokes, and translation of neuroprotective drug effects seen in animals to humans has been disappointing. If haptoglobin is found in human brains, augmenting the protein’s natural protection ability may prove more effective than traditional pharmacological approaches

X. Zhao et al., Neuroprotective role of haptoglobin after intracerebral hemorrhage. J. Neurosci. 29, 15819–15827 (2009). [Abstract]

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