Abstract |
Neurolathyrism (NL) is a motor neuron disease characterized by spastic paraparesis in the hind legs. β-N-oxalyl-l-α,β-diaminopropionic acid (l-β- ODAP), a component amino acid of the grass pea (Lathyrus sativus L.), has been proposed as the cause of this disease. In our NL rat model, we previously reported that transient intra-parenchymal hemorrhage occurred in the lower spinal cord during the early treatment period. We show here a possible pathological role of the hemorrhage in motor neuron damage and paraparesis pathology. In the lumbo-sacral spinal cord, blood vessel integrity was lost with numerous TdT-mediated dUTP nick end-labeling-positive blood vessel-like structures occurring simultaneously with the hemorrhage. We observed a coincident >10-fold increase in heme oxygenase-1 (HO-1) only in the lower spinal cord. The early period of paraparesis in the lower leg was greatly suppressed by pretreatment with zinc protoporphyrin IX, a HO-1 inhibitor. In vitro, l-β- ODAP was toxic to human umbilical vein endothelial cells compared to l-glutamate. The present data shed light on the role and the mechanism of vascular insult in causing dysfunction and moribund motor neurons in experimental NL.
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Authors | Kimino Kawaguchi, Fernand Lambein, Kuniko Kusama-Eguchi |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 428
Issue 1
Pg. 160-6
(Nov 09 2012)
ISSN: 1090-2104 [Electronic] United States |
PMID | 23068093
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Elsevier Inc. All rights reserved. |
Chemical References |
- 3-N-oxalyl-L -2,3-diaminopropanoic acid
- beta-Alanine
- Heme Oxygenase-1
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Topics |
- Animals
- Blood Vessels
(enzymology, injuries)
- Disease Models, Animal
- Heme Oxygenase-1
(biosynthesis)
- Hemorrhage
(chemically induced, complications, enzymology)
- Human Umbilical Vein Endothelial Cells
(drug effects)
- Humans
- Lathyrism
(etiology, pathology, physiopathology)
- Lumbosacral Region
- Motor Neurons
(enzymology, pathology)
- Paraparesis
(etiology, pathology, physiopathology)
- Rats
- Rats, Wistar
- Spinal Cord
(blood supply, enzymology, pathology)
- beta-Alanine
(analogs & derivatives, toxicity)
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