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.
Rastogi
Leena
L
Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014, India.
Gupta
Sushil
S
Godbole
Madan M
MM
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002545:Brain Ischemia / Q000150:complications* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology*; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009460:Neurologic Examination; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D012307:Risk Factors; D013194:Staining and Labeling; D013971:Thyrotoxicosis / Q000139:chemically induced / Q000150:complications*; D013974:Thyroxine / Q000008:administration & dosage / Q000097:blood; D013997:Time Factors
D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D013974:Thyroxine