Temporal Expression of Cytokines and Signal Transducer and Activator of Transcription Factor 3 Activation after Neonatal Hypoxia/Ischemia in Mice

2013 ◽  
Vol 35 (2-3) ◽  
pp. 212-225 ◽  
Author(s):  
K. Shrivastava ◽  
G. Llovera ◽  
M. Recasens ◽  
M. Chertoff ◽  
L. Giménez-Llort ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Signal Transducer ◽  
Temporal Expression ◽  
Neonatal Hypoxia ◽  
Hypoxia Ischemia ◽  
Transcription Factor 3

Inhibition of Signal Transducer and Activator Transcription Factor 3 in Rats with Acute Hepatic Failure

2000 ◽  
Vol 273 (1) ◽  
pp. 129-135 ◽  
Author(s):  
Yukio Kamohara ◽  
Nozomu Sugiyama ◽  
Toru Mizuguchi ◽  
Daniel Inderbitzin ◽  
Helene Lilja ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Hepatic Failure ◽  
Acute Hepatic Failure ◽  
Signal Transducer ◽  
Transcription Factor 3

scholarly journals The roles of signal transducer and activator of transcription factor 3 in tumor angiogenesis

Oncotarget ◽  
2017 ◽  
Vol 8 (40) ◽  
pp. 69139-69161 ◽  
Author(s):  
Peng Gao ◽  
Na Niu ◽  
Tianshu Wei ◽  
Hideto Tozawa ◽  
Xiaocui Chen ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Tumor Angiogenesis ◽  
Signal Transducer ◽  
Transcription Factor 3

scholarly journals Melatonin and/or erythropoietin combined with hypothermia in a piglet model of perinatal asphyxia

2020 ◽  
Author(s):  
Raymand Pang ◽  
Adnan Avdic-Belltheus ◽  
Christopher Meehan ◽  
Kathryn Martinello ◽  
Tatenda Mutshiya ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Triple Therapy ◽  
Sensorimotor Cortex ◽  
Perinatal Asphyxia ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Resonance Spectroscopy ◽  
Periventricular White Matter ◽  
Deoxyuridine Triphosphate ◽  
Hypoxia Ischemia ◽  
Effective Adjunct

Abstract As therapeutic hypothermia is only partially protective for neonatal encephalopathy, safe and effective adjunct therapies are urgently needed. Melatonin and erythropoietin show promise as safe and effective neuroprotective therapies. We hypothesized that melatonin and erythropoietin individually augment 12-hour hypothermia (double therapies) and hypothermia + melatonin + erythropoietin (triple therapy) leads to optimal brain protection. Following carotid artery occlusion and hypoxia, 49 male piglets (<48 hours old) were randomized to: (i) hypothermia + vehicle (n = 12), (ii) hypothermia + melatonin (20 mg/kg over 2 hours) (n = 12), (iii) hypothermia + erythropoietin (3000 U/kg bolus) (n = 13) or (iv) triple therapy (n = 12). Melatonin, erythropoietin or vehicle were given at 1, 24 and 48 hours after hypoxia-ischemia. Hypoxia-ischemia severity was similar across groups. Therapeutic levels were achieved 3 hours after hypoxia-ischemia for melatonin (15-30mg/L) and within 30 minutes of erythropoietin administration (maximum concentration 10,000 mU/mL). Compared to hypothermia + vehicle, we observed faster amplitude integrated EEG recovery from 25-30 hours with hypothermia + melatonin (p = 0.02) and hypothermia + erythropoietin (p = 0.033) and from 55-60 hours with triple therapy (p = 0.042). Magnetic Resonance Spectroscopy Lactate/N-acetyl aspartate peak ratio was lower at 66 hours in hypothermia + melatonin (p = 0.012) and triple therapy (p = 0.032). With hypothermia + melatonin, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelled-positive cells were reduced in sensorimotor cortex (p = 0.017) and oligodendrocyte transcription factor 2 labelled-positive counts increased in hippocampus (p = 0.014) and periventricular white matter (p = 0.039). There was no reduction in terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelled-positive cells with hypothermia + erythropoietin, but increased oligodendrocyte transcription factor 2 labelled-positive cells in 5 of 8 brain regions (p < 0.05). Overall, melatonin and erythropoietin were safe and effective adjunct therapies to hypothermia. Hypothermia + melatonin double therapy led to faster amplitude integrated EEG recovery, amelioration of Lactate/N-acetyl aspartate rise and reduction in terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelled-positive cells in the sensorimotor cortex. Hypothermia + erythropoietin double therapy was association with EEG recovery and was most effective in promoting oligodendrocyte survival. Triple therapy provided no added benefit over the double therapies in this 72-hour study. Melatonin and erythropoietin influenced cell death and oligodendrocyte survival differently, reflecting distinct neuroprotective mechanisms which may become more visible with longer term studies. Staggering the administration of therapies with early melatonin and later erythropoietin (after hypothermia) may provide better protection; each therapy has complementary actions which may be time critical during the neurotoxic cascade after hypoxia-ischemia.

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