dinoprost and Cerebral-Hemorrhage

MicroRNAs (miRNAs) have important contributions to multiple pathophysiological processes for cellular response to stress and are considered as promising therapeutic targets with respect to drug development due to their small size, relative ease of delivery, and sequence specificity. Thus, in the current report, we examined the effects of inhibiting miRNA-155 (miR-155) on the levels of pro-inflammatory cytokines (PICs), oxidative stress products as well as vascular endothelial growth factor (VEGF) in the parietal cortex and hippocampus of rats following intracerebral haemorrhage (ICH). Real time PCR was used to examine the levels of miR-155 in the parietal cortex and hippocampus of rats; and ELISA to measure IL-1β, IL-6 and TNF-α, oxidative 8-iso PGF2α and 8-OHdG, and VEGF. Additionally, modified neurological Severity Score (mNSS) was examined to indicate neurological function in animals. In results, with induction of ICH, the levels of miR-155 were amplified in the parietal cortex and hippocampus and this was accompanied with increases of IL-1β, IL-6 and TNF-α; and 8-iso PGF2α and 8-OHdG. Intracerebroventricular infusion of miR-155 inhibitor attenuated the elevation of PICs and amplification of oxidative stress products. Interestingly, miR-155 inhibitor promoted VEGF levels. Furthermore, inhibition of miR-155 led to improvement of neurological deficits in ICH rats. In conclusion, miR-155 signal in the parietal cortex and hippocampus is engaged in the processes of neural injury during ICH and blocking central miR-155 pathway plays a beneficial role in regulating neurological function via reduction in PICs and products of oxidative stress; and enhancement of VEGF. This has implications to target miR-155 and its downstream signal pathway for neuronal dysfunction and vulnerability related to ICH.

Topics: Animals; Cerebral Hemorrhage; Cytokines; Dinoprost; Interleukin-6; MicroRNAs; Neuroinflammatory Diseases; Oxidative Stress; Rats; Rats, Sprague-Dawley; Signal Transduction; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

Iron plays a key role in secondary neuronal injury after intracerebral hemorrhage (ICH), and hepcidin is able to reduce brain iron in iron-overloaded rats by down-regulating iron transport proteins including ferroportin 1 and transferrin receptor 1. These led us to hypothesize that hepcidin might reduce iron-mediated neurotoxicity by inhibiting iron accumulation in ICH brain. Here, we examined effects of Ad-hepcidin (hepcidin expression adenovirus) on the nonheme iron contents, expression of hepcidin, ferritin and iron transport proteins, neuronal cell survival, water contents in the brain and/or cerebrospinal fluid (CSF), and ICH-induced apoptosis, neurological deficit by RT-PCR, Western blot analysis, NeuN Immunofluorescence, TUNEL, Fluoro-Jade B staining, behavioral performance and Morris water-maze tests in 510 rats. We demonstrated that hepcidin could significantly suppress the ICH-induced increase in iron and ferritin in brain tissues and CSF by inhibiting expression of iron transport proteins, increase neuronal survival by attenuating ICH-induced apoptosis, reactive oxygen species, neurodegeneration and brain edema, as well as effectively improve ICH-induced behavioral and cognitive deficit in rats. The findings collectively showed that hepcidin could effectively attenuate iron-mediated secondary neuronal injury after ICH in rats. This naturally existing protein can potentially be developed into a therapeutic drug for the treatment of ICH patients.

Topics: Adenoviridae; Animals; Apoptosis; Behavior, Animal; Brain Edema; Cation Transport Proteins; Cell Survival; Cerebral Hemorrhage; Corpus Striatum; Dinoprost; Gene Expression; Hepcidins; Iron; Male; Neurons; Rats, Sprague-Dawley; Receptors, Transferrin; Recombinant Proteins

Higher plasma 8-iso-Prostaglandin F2α concentrations have been associated with poor outcome of severe traumatic brain injury. We further investigated the relationships between plasma 8-iso-Prostaglandin F2α concentrations and clinical outcomes in patients with acute intracerebral hemorrhage.. Plasma 8-iso-Prostaglandin F2α concentrations of 128 consecutive patients and 128 sex- and gender-matched healthy subjects were measured by enzyme-linked immunosorbent assay. We assessed their relationships with disease severity and clinical outcomes including 1-week mortality, 6-month mortality and unfavorable outcome (modified Rankin Scale score>2).. Plasma 8-iso-Prostaglandin F2α concentrations were substantially higher in patients than in healthy controls. Plasma 8-iso-Prostaglandin F2α concentrations were positively associated with National Institutes of Health Stroke Scale (NIHSS) scores and hematoma volume using a multivariate linear regression. It emerged as an independent predictor for clinical outcomes of patients using a forward stepwise logistic regression. ROC curves identified the predictive values of plasma 8-iso-Prostaglandin F2α concentrations, and found its predictive value was similar to NIHSS scores and hematoma volumes. However, it just numerically added the predictive values of NIHSS score and hematoma volume.. Increased plasma 8-iso-Prostaglandin F2α concentrations are associated with disease severity and clinical outcome after acute intracerebral hemorrhage.

Topics: Acute Disease; Aged; Biomarkers; Cerebral Hemorrhage; Dinoprost; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mortality; Stroke; Treatment Outcome

To evaluate whether uterotrophic agents increase the risk of fatal hemorrhagic brain stroke.. Between 1991 and 1992, there were 230 maternal deaths among 2,420,000 pregnant women in Japan and the causes of these deaths was investigated in 1994. Using information provided in this report, we identified 35 women who died from or were assumed to die from hemorrhagic brain stroke. We assumed that 93% of women would have tried vaginal delivery. The risk of fatal hemorrhagic brain stroke after uterotrophic agent use was calculated according to the assumption that 5.0-40% of women received uterotrophic agents.. Use of uterotrophic agents for induction/augmentation of labor was confirmed in five (14.3%) of the 35 women who died from hemorrhagic brain stroke. The incidence of fatal brain stroke after the use of uterotrophic agents was only significantly higher than that for spontaneous hemorrhagic brain stroke if these agents were administered in ≤ 6.0% of women.. Because more than 6.0% of women received uterotrophic agents, these agents are unlikely to increase the risk of fatal hemorrhagic brain stroke.

Topics: Cerebral Hemorrhage; Dinoprost; Dinoprostone; Female; Humans; Japan; Oxytocics; Oxytocin; Pregnancy; Risk Assessment; Stroke

The goal of this study was to determine the alterations in contractile and dilatory responses and ultrastructure of the feline middle cerebral artery after hemorrhagic hypotension.. In the sodium pentobarbital anesthetized cats, a steady 50 mm Hg level of hypotension was reached by bleeding into a reservoir and maintained at this level by further bleeding or autotransfusion for 2 hours. Rings of the arteries, from control animals and from animals after hypotension, were suspended for isometric tension recording in organ chambers filled with modified Krebs-Henseleit solution, aerated with 95% O2-5% CO2 at 37 degrees C, and their reactions to contractile and relaxant agents were tested. Vascular ultrastructure was studied by electron microscope.. Endothelium-dependent relaxations induced by 10(-8) M acetylcholine were enhanced, whereas there was a marked inhibition of the relaxation at 10(-6) M. Relaxations induced by adenosine triphosphate and adenosine showed an impairment. Contractions induced by norepinephrine and prostaglandin F2 alpha remained unchanged, whereas 5-hydroxytryptamine caused a more pronounced contraction after hypotension. No alterations in the morphology of endothelium or smooth muscle were found after hemorrhage. There was, however, a marked decrease in the number of transmitter vesicles in the perivascular nerve terminals.. The present results show marked alterations in cerebrovascular reactivity and ultrastructure of the adventitia after hypotension. These alterations might play an important role in the development of cerebral vasoconstriction during and after this hemorrhagic state.

Topics: Acetylcholine; Adenosine; Adenosine Triphosphate; Animals; Cats; Cerebral Arteries; Cerebral Hemorrhage; Dinoprost; Female; Hypotension; Male; Norepinephrine; Serotonin; Vasoconstriction; Vasodilation

The cerebrospinal fluid (CSF) of 11 premature infants suffering from posthemorrhagic hydrocephalus was examined by radioimmunoassay for prostaglandin (PG) E2, PGF2 alpha, PGD2, 6-keto PGF1 alpha, thromboxane B2 (TxB2) and peptidoleukotrienes (LTC4/LTD4). The LTs were detected in the CSF of more of these patients (70%) than any of the other eicosanoids, and usually in the highest concentration. Among the 11 posthemorrhagic patients CSF eicosanoid levels were highest when determined soon after injury. Moreover, the variety of eicosanoids present, as well as concentrations, in these infants decreased with time. The types of eicosanoids most evident in the CSF of patients who required shunting were TxB2 and LTs, being present together in 5 of 6 (83%) of these infants. In contrast, 1 of 5 (20%) of the patients who did not require this neurosurgical intervention contained both TxB2 and LTs, the remaining having only one or neither eicosanoid. The highest average concentration for each eicosanoid studied was (pg/ml): PGE2, 628; PGF2 alpha, 985; PGD2, 1410; 6-keto PGF1 alpha, 544; TxB2, 486 and LTs, 1229. This study is the first to demonstrate that the CSF of preterm infants may contain a wide variety of eicosanoids and indicates that these lipids are a manifestation of neurological assault.

Topics: 6-Ketoprostaglandin F1 alpha; Cerebral Hemorrhage; Dinoprost; Dinoprostone; Eicosanoids; Humans; Hydrocephalus; Infant, Newborn; Infant, Premature, Diseases; Leukotrienes; Prostaglandin D2; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Cerebral Hemorrhage; Dinoprost; Humans; Hypoxia, Brain; Infant, Newborn

A neuropathological examination was carried out on the brains of 58 foals. Forty-two were pony foals induced at various periods of gestation from 200 days onwards. Two were pre-viable pony foals delivered by caesarean section and 14 were Thoroughbred foals (one set of twins, two stillborn, five premature, two dysmature, two convulsive and one induced). The only significant pathological change involved intracranial haemorrhage. Subarachnoid haemorrhage occurred in all of 10 pony foals induced before 301 days of gestation and in two pony foals born by caesarean section at 270 and 280 days gestation. Subarachnoid haemorrhage was also present in some pony and Thoroughbred foals born after 301 days gestation; the incidence usually appeared greater in those pony foals which survived for the shortest periods. Haemorrhage also occurred elsewhere in the brains, including the cerebral white matter, the molecular layer of the cerebellum and the medulla, but the intensity could not be related to either length of gestation or duration of survival. No other neuropathological changes were found that could account for the functional state of the animals, whether they were pre-viable, premature, dysmature or convulsive.

Topics: Animals; Animals, Newborn; Brain; Cerebral Hemorrhage; Dinoprost; Female; Fetal Death; Horse Diseases; Horses; Labor, Induced; Luteolytic Agents; Pregnancy; Prostaglandins F; Prostaglandins F, Synthetic