Oral administration of a neuroprotective compound T-588 prevents motoneuron degeneration after facial nerve avulsion in adult rats.

Abstract

OBJECTIVE:

R(-)-1-(benzo[b]thiophen-5-yl)-2-[2-(N,N-diethylamino) ethoxylethanol hydrochloride (T-588), a synthetic compound, has been shown to have neuroprotective potentials for neuronal cells. We investigated whether orally administered T-588 can rescue injured motoneurons after facial nerve avulsion in adult rats.

METHODS:

The right facial nerves of adult Fischer 344 male rats were avulsed and the animals were freely administered solution of 0.05% (w/v) T-588 or received T-588 (3-30 mg/kg/day) through an oral tube for 1-4 weeks. Facial motoneurons on both sides of the facial nuclei were counted in Nissl-stained sections, and choline acetyltransferase (ChAT) immunoreactivity in injured motoneurons and ChAT enzyme activities in the ventral brain stem tissue containing the facial nuclei were examined.

RESULTS:

Both free oral administration of 0.05% T-588 solution and oral tube administration of T-588 (30mg/kg/day) improved the survival of facial motoneurons at 3 or 4 weeks after avulsion. These treatments ameliorated ChAT immunoreactivity in injured motoneurons and the tissue ChAT enzyme activities at 1-week postoperation examined.

CONCLUSION:

These results indicate that oral administration of T-588 ameliorates the survival of injured motoneurons and supports their neuronal function after facial nerve avulsion in adult rats. T-588 may have therapeutic potential in motoneuron injury or motor neuron diseases in humans.

• Authors: Ken Ikeda, Tsuyoshi Sakamoto, Shigeki Marubuchi, Yoko Kawazoe, Nobuo Terashima, Yasuo Iwasaki, Masao Kinoshita, Satoshi Ono, Masaya Nakagawa, Kazuhiko Watabe
• Journal: Amyotrophic lateral sclerosis and other motor neuron disorders : official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases (Amyotroph Lateral Scler Other Motor Neuron Disord) Vol. 4 Issue 2 Pg. 74-80 (Jun 2003) ISSN: 1466-0822 [Print] England
• PMID: 14506937 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Diethylamines
• Glial Fibrillary Acidic Protein
• Lectins
• Neuroprotective Agents
• Thiophenes
• T 588
• Choline O-Acetyltransferase

Topics

• Administration, Oral
• Age Factors
• Animals
• Body Weight
• Cell Survival (drug effects)
• Choline O-Acetyltransferase (analysis)
• Diethylamines (chemistry, pharmacology)
• Facial Nerve Injuries (drug therapy, pathology)
• Glial Fibrillary Acidic Protein (analysis)
• Immunohistochemistry
• Lectins (analysis)
• Male
• Motor Neuron Disease (drug therapy, pathology, prevention & control)
• Motor Neurons (chemistry, enzymology, pathology)
• Neuroprotective Agents (chemistry, pharmacology)
• Rats
• Rats, Inbred F344
• Thiophenes (chemistry, pharmacology)