Gender differences in isoflurane preconditioning and experimental stroke

Introduction

In male rats ¹ and mice ² , pretreatment with isoflurane 24 hours before experimental stroke was shown to be neuroprotective. However, it is unknown if males and females respond differently to anesthetic preconditioning (AP) in the context of cerebral ischemia. There are some reported gender differences in terms of clinical and experimental responses to specific anesthetics but sex differences in anesthetic applications have been understudied. The choice of anesthetic in clinical patients would be important in cases where CNS damage is anticipated peri-operatively, such as in neurosurgery or cardiac bypass surgery. AP may therefore prevent or even delay neurological complications, thereby increasing the therapeutic window for other prospective neuroprotective agents. In this study, we determined if there is a gender difference in isoflurane preconditioning (IPC) of the brain before transient focal cerebral ischemia.

Methods

Mice were preconditioned for 4 hours with 1% isoflurane (IPC) or no anesthetic (sham PC) in an air tight, temperature-controlled chamber. Animals were then recovered for 24 hours. Each animal subsequently underwent 120 minutes of MCAO by the intraluminal filament technique ³ followed by 22 hours reperfusion. Cortical (CTX), caudate-putamen (CP), and total hemispheric (TTL) infarct volumes were determined by digital image analysis of sequential 2 mm thick coronal slices of brain stained with 2,3,5-triphenyltetrazolium chloride. Laser-Doppler flowmetery (LDF) was used to estimate ischemic reduction of cortical perfusion at initiation of occlusion and restoration of blood flow during reperfusion.

Results

Rectal temperatures were maintained within normal physiological range and were equivalent among groups. Results of CTX infarct volumes are shown in figure 1. CP and TTL infarct volumes showed a similar pattern of results between treatment groups. LDF at induction of MCAO and at initiation of reperfusion were equivalent among treatment groups. All data are mean ± SEM. *p<0.05.

Figure 1

Conclusions

Isoflurane preconditioning is protective in ischemic male mouse brain but worsened infarct outcome in females. Ovariectomized female mice had comparable neuroprotection from isoflurane preconditioning as the males, suggesting that female sex steroids may alter ischemic outcome in response to isoflurane preconditioning.