http://jap.physiology.org/content/92/1/195.short
Abstract
Increasing evidence has demonstrated
striking sex differences in the outcome of neurological injury. Whereas
estrogens contribute
to these differences by attenuating neurotoxicity
and ischemia-reperfusion injury, the effects of testosterone are
unclear.
The present study was undertaken to determine the
effects of testosterone on neuronal injury in both a cell-culture model
and a rodent ischemia-reperfusion model.
Glutamate-induced HT-22 cell-death model was used to evaluate the
effects of testosterone
on cell survival. Testosterone was shown to
significantly increase the toxicity of glutamate at a 10 μM
concentration, whereas
17β-estradiol significantly attenuated the toxicity
at the same concentration. In a rodent stroke model,
ischemia-reperfusion
injury was induced by temporal middle cerebral
artery occlusion (MCAO) for 1 h and reperfusion for 24 h. To avoid the
stress-related
testosterone reduction, male rats were castrated
and testosterone was replaced by testosterone pellet implantation.
Testosterone
pellets were removed at 1, 2, 4, or 6 h before MCAO
to determine the duration of acute testosterone depletion effects on
infarct
volume. Ischemic lesion volume was significantly
decreased from 239.6 ± 25.9 mm3 in control to 122.5 ± 28.6 mm3
when testosterone pellets were removed at 6 h before MCAO. Reduction of
lesion volume was associated with amelioration of
the hyperemia during reperfusion. Our in vitro and
in vivo studies suggest that sex differences in response to brain injury
are partly due to the consequence of damaging
effects of testosterone.
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