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

Abstract

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.

Prognostic value of thyroid hormones in acute ischemic stroke – a meta analysis

“…Another study found a reduced neurological deficit, smaller infarct size, and fewer apoptotic neurons in hypothyroid ischemic rats 41 . Meanwhile two studies indicated that hyperthyroidism accelerated post-stroke injury in a rat model 42 , 43 . After reviewing the studies above, we must point out that in animal experiments 32 – 39 , the subjects were given exogenous T3 or T4 within hours of the induction of brain ischemia to explore the influence of thyroid hormone variation during the acute ischemic period, but in other studies 40 – 43 hypothyroidism/hyperthyroidism was induced weeks before the establishment of the ischemic model, which thus involved the previous cumulative effect on the nervous system of abnormal thyroid function.…”

“…Meanwhile two studies indicated that hyperthyroidism accelerated post-stroke injury in a rat model 42 , 43 . After reviewing the studies above, we must point out that in animal experiments 32 – 39 , the subjects were given exogenous T3 or T4 within hours of the induction of brain ischemia to explore the influence of thyroid hormone variation during the acute ischemic period, but in other studies 40 – 43 hypothyroidism/hyperthyroidism was induced weeks before the establishment of the ischemic model, which thus involved the previous cumulative effect on the nervous system of abnormal thyroid function. Disappointingly, we only found one study that conducted a clinical trial on human patients, the results of which suggested that the use of thyroliberin (TRH) can inhibit “low T3 syndrome” and alleviate neurological deficit in the acute stage of ischemic stroke 44 .…”

Molecular Basis for Certain Neuroprotective Effects of Thyroid Hormone

“…Subsequently, it was shown that experimental hyperthyroidism that is established before focal ischemia may increase neuronal insult in the rat (Rastogi et al, 2008). Thus, any neuronal rescue that may occur with thyroid hormone administration must avoid induction of hypermetabolism.…”

Influence of thyroid states on the local effects induced by Bothrops envenoming

“…Experimental hyperthyroidism was induced in animals for 7 days by daily subcutaneous injections (300 mg/kg) of L-thyroxine (T4; Sigma Chemical Company, St. Louis, MO, USA), resulting in a thyrotoxic state (Basset et al, 2000;Rastogi et al, 2008;Ribeiro et al, 2012). The control animals received daily subcutaneous injections of saline for 7 days.…”