Impaired limb reaction to displacement of center of gravity in rats with unilateral striatal ischemic injury.

Clinical stroke often results in impaired balance and increased vulnerability to severe injuries due to falling. To evaluate potential preclinical treatments that might target these deficits, it will be important to include tests capable of assessing these impairments chronically in animal models. Previously, we developed a postural instability test (PIT) that revealed chronic, unilateral impairments in postural stability in rat models of hemi-Parkinson's disease (PD) and of unilateral cervical spinal cord injury. Here, we investigated whether this test was also capable of revealing long-term stroke-induced impairments in postural support in rats. Additionally, we examined the ability of more common tests of sensorimotor function to detect chronic impairments. We found that the PIT detected chronic deficits in postural stability/balance enduring for up to 6 weeks post-stroke, outlasting impairments detected in other tests of forelimb sensorimotor function, including asymmetries in upright postural support (cylinder test) and vibrissae-evoked forelimb placing.

Dose-dependent effects of androgens on outcome after focal cerebral ischemia in adult male mice.

Males exhibit greater histologic and behavioral impairment after stroke than do age-matched females. However, the contribution of androgens to stroke outcome remains unclear. We compared outcomes from middle cerebral artery occlusion (MCAO) in castrated mice with those in testosterone- or dihydrotestosterone (DHT)-replaced castrated mice. Castrates treated with 1.5 mg testosterone or 0.5 mg DHT before MCAO showed smaller infarct volumes (hemisphere: 27 or 26%) at 24 h after 90 mins MCAO than did untreated castrates (37%), whereas 5 mg testosterone or 1.5 mg DHT exacerbated infarcts (53 or 51%). These outcomes were blocked by the androgen receptor antagonist, flutamide, suggesting that androgen receptors mediate these responses to ischemia. We further evaluated long-term outcomes with a milder 60-min MCAO in castrates treated with the protective 1.5 mg testosterone dose. Consistent with data obtained at 24 h reperfusion, the infarct volume was decreased at 9 days reperfusion. Neurobehavioral analysis showed that motor functional recovery was improved during the first 3 days of reperfusion, but not improved at 7 days. We conclude that testosterone exhibits dose-dependent and time-sensitive effects after ischemia and that testosterone is likely to be an important factor in sex-linked differences in cerebrovascular disease.