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


CONCLUSIONS
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.
D000284:Administration, Oral; D000367:Age Factors; D000818:Animals; D001835:Body Weight; D002470:Cell Survival / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000032:analysis; D004048:Diethylamines / Q000737:chemistry / Q000494:pharmacology*; D020220:Facial Nerve Injuries / Q000188:drug therapy* / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007150:Immunohistochemistry; D037102:Lectins / Q000032:analysis; D008297:Male; D016472:Motor Neuron Disease / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D009046:Motor Neurons / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology*
D004048:Diethylamines; D005904:Glial Fibrillary Acidic Protein; D037102:Lectins; D018696:Neuroprotective Agents; D013876:Thiophenes; C082372:T 588; D002795:Choline O-Acetyltransferase