Pathophysiological basis for thyrotoxicosis as an aggravating factor in post-ischemic brain injury in rats.

The cross-sectional epidemiological studies investigating hyperthyroidism as a risk factor for hypertension and stroke are not conclusive. Several case studies, however, indicate that persistent thyrotoxicosis aggravates neurological damage subsequent to a stroke. To test the hypothesis, we measured physiological and biochemical parameters in a model of transient focal ischemia in rats with prior induction of thyrotoxicosis to investigate its effects. Age- and weight-matched rats were made hyperthyroid prior to middle cerebral artery (MCA) occlusion and killed after 3 days of reperfusion. We then estimated neurological deficit scores, body temperature, circulating total and free thyroxine (fT(4)) levels, lipid peroxide and thiol levels, and lactate dehydrogenase activity. While the standard 2-h occlusion of MCA resulted in very high mortality in hyperthyroid animals, the 30-min MCA occlusion resulted in a significant increase in neurological deficits compared with sham-operated animals. We observed a twofold or more increase in circulating fT(4) levels in rats receiving thyroxine. The increase in infarct size directly correlated with the increased dose of thyroxine. A significant thyroxine dose-dependent increase in lipid peroxide (malondialdehyde levels, P<0.05), lactate dehydrogenase activity (P<0.01), and a significant decrease in protective thiol levels (P<0.05) were observed. The data support our hypothesis that thyrotoxicosis is an independent risk factor which contributes to the aggravation of post-stroke injury and death. The study results indicate a need to control thyrotoxicosis in elderly populations to reduce the risk.