Oral administration of metal chelator ameliorates motor dysfunction after a small hemorrhage near the internal capsule in rat

Tadashi Masuda; Hideki Hida; Yoshie Kanda; Noritaka Aihara; Kengo Ohta; Kazuo Yamada; Hitoo NISHINO

doi:10.1002/jnr.21089

journal article Oct 23, 2006

Oral administration of metal chelator ameliorates motor dysfunction after a small hemorrhage near the internal capsule in rat

Tadashi Masuda Hideki Hida Yoshie Kanda Noritaka Aihara Kengo Ohta Kazuo Yamada Hitoo NISHINO

Journal of Neuroscience Research Vol. 85 No. 1 pp. 213-222 · Wiley

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Abstract

AbstractCerebral hemorrhage leads to local production of free iron, radicals, cytokines, etc. To investigate whether a decrease of iron‐mediated radical production influences functional recovery after intracerebral hemorrhage (ICH), a modified ICH rat model with a small hemorrhage near the internal capsule (IC) accompanied with relatively severe motor dysfunction was first developed. Then clioquinol (CQ), an iron chelator that reduces hydroxyl radical production, was orally administrated. Injection of different doses of Type IV collagenase (1.4 μl 1–200 U/ml) into the left striatum near the IC in Wistar rats showed that injection of 7.5 U/ml collagenase resulted in a small hemorrhoidal lesion near the IC with relatively severe motor dysfunction (IC model). Retrograde labeling of neurons in the sensory‐motor cortex and axons in the corticospinal tract using Fluoro‐gold (FG) injection into the spinal cord (C3–C4) showed that few labeled neurons in the sensory‐motor cortex were detected in the IC model, FG‐labeled axons disappeared, and FG‐including ED‐1‐positive cells appeared within 24 hr in the IC. Assessments of behavior and histologic analysis after oral administration of CQ in the IC model indicated that oral administration of CQ prevented a decrease of FG‐labeled neurons, and resulted in better motor‐function recovery. CQ inhibited hydrogen peroxide‐induced cell toxicity in oligodendrocytes in vitro, but not in neurons. Our data suggests that CQ ameliorated motor dysfunction after a small hemorrhage near the IC by a mechanism that is related to reduction of chain‐reactive hydroxyl radical production in oligodendrocytes. © 2006 Wiley‐Liss, Inc.

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Published: Oct 23, 2006
Vol/Issue: 85(1)
Pages: 213-222
License: View

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Cite This Article

Tadashi Masuda, Hideki Hida, Yoshie Kanda, et al. (2006). Oral administration of metal chelator ameliorates motor dysfunction after a small hemorrhage near the internal capsule in rat. Journal of Neuroscience Research, 85(1), 213-222. https://doi.org/10.1002/jnr.21089

Oral administration of metal chelator ameliorates motor dysfunction after a small hemorrhage near the internal capsule in rat

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