Our own study as well as others have previously reported that hypoxia activates 15-lipoxygenase (15-LO) in the brain, causing a series of chain reactions, which exacerbates ischemic stroke. 15-hydroxyeicosatetraenoic acid (15-HETE) and 15-oxoeicosatetraenoic acid (15-oxo-ETE/15-KETE) are 15-LO-specific metabolites of arachidonic acid (AA). 15-HETE was found to be rapidly converted into 15-oxo-ETE by 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in some circumstances. We have demonstrated that 15-HETE promotes cerebral vasoconstriction during hypoxia. However, the effect of 15-oxo-ETE upon the contraction of cerebral vasculature remains unclear. To investigate this effect and to clarify the underlying mechanism, we performed immunohistochemistry and Western blot to test the expression of 15-PGDH in rat cerebral tissue, examined internal carotid artery (ICA) tension in isolated rat ICA rings. Western blot and reverse transcription polymerase chain reaction (RT-PCR) were used to analyze the expression of voltage-gated potassium (Kv) channels (Kv2.1, Kv1.5, and Kv1.1) in cultured cerebral arterial smooth muscle cells (CASMCs). The results showed that the levels of 15-PGDH expression were drastically elevated in the cerebral of rats with hypoxia, and 15-oxo-ETE enhanced ICA contraction in a dose-dependent manner. This effect was more significant in the hypoxic rats than in the normoxic rats. We also found that 15-oxo-ETE significantly attenuated the expression of Kv2.1 and Kv1.5, but not Kv1.1. In conclusion, these results suggest that 15-oxo-ETE leads to the contraction of the ICA, especially under hypoxic conditions and that specific Kv channels may play an important role in 15-oxo- ETE-induced ICA constriction., Di Wang, Yu Liu, Ping Lu, Daling Zhu, Yulan Zhu., and Obsahuje bibliografii
Neonatal hypoxic-ischemic encephalopathy is a disorder with heterogeneous manifestation due to asphyxia during perinatal period. It affects approximately 3-12 children per 1000 live births and cause death of 1 million neonates worldwide per year. Besides, motor disabilities, seizures, impaired muscle tone and epilepsy are few of the consequences of hypoxic-ischemic encephalopathy. Despite an extensive research effort regarding various treatment strategies, therapeutic hypothermia with intensive care unit supportive treatment remains the only approved method for neonates who have suffered from moderate to severe hypoxicischemic encephalopathy. However, these protocols are only partially effective given that many infants still suffer from severe brain damage. Thus, further research to systematically test promising neuroprotective treatments in combination with hypothermia is essential. In this review, we discussed the pathophysiology of hypoxic-ischemic encephalopathy and delved into different promising treatment modalities, such as melatonin and erythropoietin. However, preclinical studies and clinical trials are still needed to further elucidate the mechanisms of action of these modalities.
This study aimed to evaluate the changes in the erythropoietin
level and hematological variables in wrestlers after intermittent
hypoxic exposure (IHE). Twelve wrestlers were assigned into two
groups: hypoxia (sports training combined with IHE, n=6) and
control (sports training, n=6). An IHE was performed for
10 days, with one day off after 6 days, once a day for about
an hour. The concentrations of hydrogen peroxide (H2O2),
nitric oxide (NO), vascular endothelial growth factor (VEGF)
and erythropoietin (EPO), as well as total creatine kinase
activity (CK) were measured. Also, the hematological markers
(Hb -hemoglobin, Ht - hematocrit, RBC - red blood cell, WBC -
white blood cell, Ret - reticulocytes) were analyzed. The 6-day
IHE caused an increase in the levels of H2O2, NO and VEGF.
Similarly, the EPO level and WBC count reached the highest value
after 6 days of IHE. The total Ret number increase constantly
during 10 days of IHE. The hypoxia group showed a higher CK
activity compared to the control. In conclusion, 10-day IHE in
combination with wrestling training elevates levels of H2O2, NO
and VEGF, and improves the oxygen transport capacity by the
release of EPO and Ret in circulation.