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The present study investigated the effects of hypothyroidism on cyclooxygenase‑2 (COX‑2) and pro‑inflammatory cytokines in the dentate gyrus to elucidate the roles of COX‑2 in the hypothyroid hippocampus. Hypothyroidism was induced in rats by treating with 0.03% 2‑mercapto‑1‑methyl‑imidazole dissolved in drinking water for 5 weeks. The animals were sacrificed at 12 weeks of age. Hypothyroidism rats exhibited decreased triiodothyronine and thyroxine levels in the serum, while the levels of thyroid‑stimulating hormone and the weight of thyroid glands were significantly higher in the hypothyroid rats compared with those in the vehicle‑treated group. COX‑2 immunoreactivity was significantly increased in the hippocampal CA2/3 region and the dentate gyrus compared with the vehicle‑treated group. Levels of pro‑inflammatory cytokines including interleukin (IL)‑1β, IL‑6 and tumor necrosis factor‑α were significantly higher in the hippocampal homogenates of hypothyroid rats. Cell proliferation and neuroblast differentiation based on Ki67 and doublecortin immunohistochemistry were decreased in the dentate gyrus of hypothyroid rats compared with those in the vehicle‑treated group. These results suggested that hypothyroidism‑mediated COX‑2 expression affected hippocampal plasticity by upregulating the levels of pro‑inflammatory cytokines in the hippocampus. Therefore, COX‑2 may be suggested as a candidate molecule for preventing hypothyroidism‑induced neurological side effects. [ABSTRACT FROM AUTHOR]

Neurotrophin 4 (NT-4) belongs to the family of neurotrophic factors, and it interacts with the tyrosine kinase B (trkB) receptor. NT-4 has neuroprotective effects following cerebral ischemia. Its role might be similar to brain-derived neurotrophic factor (BDNF), because both interact with trkB. Exercise also improves neural function by increasing neurotrophic factors. However, expression profiles of NT-4 in the brain during exercise are unknown. Here, we assessed the expressions of NT-4 and its receptor, trkB, following cerebral ischemia and hypothesized that exercise changes the expressions of NT-4 and trkB. Results showed that in a permanent middle cerebral artery occlusion rat model, ischemia decreased NT-4 and trkB expression. Immunohistochemistry showed their immunoreactivities around the region of the ischemic area. Treadmill exercise changed the expression of NT-4, which increased in the contralateral hemisphere in rats with ischemic injury. TrkB also showed similar patterns to its neurotophins. The change in NT-4 suggested that exercise might have primed NT4 production so that further injury causes slightly greater increases in NT4 compared with non-exercise controls. [ABSTRACT FROM AUTHOR]

Abstract: Moderate hypothermia (25–31°C) may have a significant influence on vascular tone. We investigated the cellular mechanisms by which moderate hypothermia alters α-adrenoceptor-mediated contraction in rat thoracic aortae. Cyclooxygenase inhibition by indomethacin; nitric oxide (NO) synthase inhibition by l-NAME; potassium channel and endothelium-derived hyperpolarizing factor (EDHF) inhibition by glibenclamide and TEA; G protein inhibition by pertussis toxin; α2-adrenergic inhibition by yohimbine; and β-adrenergic inhibition by propranolol were assessed for their effect on the contractile response to the α1-adrenoceptor agonist phenylephrine (Phe) in combination with moderate hypothermia (25°C). Moderate hypothermia produced a shift to the right for the Phe concentration–response curves in endothelium-intact (E+) and endothelium-denuded (E−) aortic rings. The maximal response to Phe in E+ rings was significantly decreased (P <0.05) at 25°C compared to 38°C, whereas there was no significant difference in E− rings. Hypothermia-induced vasorelaxation in E+ rings was attenuated (P <0.05) following combined pretreatment with l-NAME (10−4 M) and indomethacin (10−5 M), whereas other inhibitors had no significant effect. Importantly, the addition of TEA to rings that were pretreated with l-NAME and indomethacin exhibited no further attenuation (P >0.05) of hypothermia-induced vasorelaxation. The concentrations of cGMP and cAMP, as measured by radioimmunoassay, were significantly increased (P <0.05) in E+ rings at 25°C compared to those at 38°C, whereas there were no significant differences (P >0.05) in E− rings. The present study demonstrated that rat aortic endothelium is stimulated during moderate hypothermia and that the NO–cGMP and prostacyclin (PGI2)–cAMP pathways represent endothelium-dependent mechanisms of hypothermia-induced vasorelaxation. In contrast, EDHF may not be associated with hypothermia-induced vasorelaxation. [Copyright &y& Elsevier]

Abstract: Activation of the trkA pathway has been widely accepted as a crucial factor for neuronal survival during cerebral ischemia. Findings from earlier studies have suggested that exercise changed neurotrophic factors and trk family in an ischemic rat model. In this study, we investigated the question of whether or not treadmill exercise improves motor function in an ischemic rat model, and whether or not the result is associated with trkA, responding to NGF. Adult male Sprague–Dawley rats underwent surgery for permanent ischemia, followed by either 12days of treadmill exercise or non-exercise. We found that exercise increased the level of trkA and NGF proteins in the contralateral hemisphere and improved the motor behavior index. Our data indicate that treadmill exercise ameliorates motor performance via the elevation of trkA and NGF proteins in the contralateral hemisphere after permanent brain ischemia. [Copyright &y& Elsevier]