Trimethyltin-induced neuropathy in the rat: interaction with thermoregulation
Gordon, C.J.; O'Callaghan, J.P.
Neurotoxicology 16(2): 319-326
1995
ISSN/ISBN: 0161-813X PMID: 7566691 Document Number: 448934
The enhanced production of glial fibrillary acidic protein (GFAP) by astroglia appears to be a general response of the CNS to many types of toxic insult. The organometallic neurotoxicant, trimethyltin (TMT), is one such agent known to increase the production of GFAP as a consequence of widespread neuronal destruction. TMT also leads to transient reductions in body temperature (T-b), a response which may alter the neurotoxic effects of this compound. To study the role of T-b in the neurotoxic effects of TMT, rats were injected (i.v.) with saline or 8.0 mg/kg TMT and maintained at ambient temperatures (T-a) of 16, 22, or 30 degree C for 72 hr while T-b (core) was measured periodically. Animals were then housed at a T-a of 22 degree C for 35 days after which time their brains were removed and dissected into hippocampus, cerebral cortex, striatum, midbrain and cerebellum for subsequent analysis of GFAP. TMT led to a significant decrease in T-b of rats housed at 22 degree C measured 3 hr after treatment. T-b of rats maintained at T-a's of 16 and 30 degree C was unaffected by TMT initially (i.e., no hypothermia); however, by 72 hr after TMT, rats maintained at 22 and 30 degree C had a significantly elevated T-b. TMT led to marked elevations in GFAP was significantly greater in rats housed at 16 and 30 degree C. A similar pattern was seen in the midbrain. It appears that the neuropathic consequences of TMT exposure, as expressed in terms of GFAP production, are affected by the transient changes in T-b brought on by exposure to this compound. The reduction in T-b by TMT appears to attenuate the rise in GFAP in certain brain areas, suggesting that TMT-induced hypothermia provides protection to the CNS during the toxic insult.