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Isoflurane Preconditioning Neuroprotection In Experimental Focal Stroke Is Androgen-Dependent In Male Mice

Zhu, Wenbin and Wang, Lan and Palmateer, Julie M and Libal, Nicole L and Hurn, Patricia D and Herson, Paco S and Murphy, Stephanie J and Imark, Esther (2010) Isoflurane Preconditioning Neuroprotection In Experimental Focal Stroke Is Androgen-Dependent In Male Mice. Neuroscience, 169 (2). pp. 758-769. ISSN 0306-4522


Isoflurane preconditioning (IsoPC) neuroprotection in experimental stroke is male-specific. The role of androgens in the ischemic sensitivity of IsoPC male brain and whether androgen effects are androgen receptor (AR) dependent were assessed. Male mice were implanted with flutamide (AR antagonist), or castrated (CAST) and implanted with testosterone, dihydroxytestosterone (DHT), flutamide, letrozole (aromatase inhibitor), or vehicle 7-13 days before preconditioning. P450 estrogen aromatase wild-type and knockout mice were also evaluated. All mice were preconditioned for 4 hours with 0% (sham preconditioning) or 1% isoflurane and recovered for 24 hours. Mice then underwent 2 hours of middle cerebral artery occlusion (MCAO) and were evaluated 22 hours later for infarct volume. For neurobehavioral outcomes, preconditioned CAST + DHT groups underwent 1 hour of MCAO followed by 9 days of reperfusion. IsoPC neuroprotection relative to acute infarct volume outcomes were testosterone and DHT dose-specific and AR-dependent. Sensorimotor function improved in IsoPC mice regardless of androgen status while androgen replacement independently improved sensorimotor function. In contrast, IsoPC improved cognitive function in castrates lacking endogenous androgens, but this improvement was absent in androgen replaced mice. Further studies are needed in ischemic male brain to clarify whether androgens have a causal or independent role in IsoPC neuroprotection.

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Date Deposited: 13 Oct 2015 13:16
Last Modified: 13 Oct 2015 13:16


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