dinoprost and Hypoxia-Ischemia--Brain

Hypoxic-ischemic encephalopathy (HIE) has deleterious neurological consequences. To identify patients at risk of neuronal damage deserving implementation of neuroprotective strategies clinicians have relied on prenatal sentinel events, postnatal clinical assessment (Apgar score), and blood gas analysis. This feasibility study aimed to assess if lipid peroxidation byproducts associated with neuronal damage correlated with cord blood metabolic acidemia in patients with HIE.. This is a case/control study in which cases were newborn infants with severe acidemia (pH<7.00; base excess ≥12mmol/L) while control babies exhibited normal gases (pH=7.20-7.40; base excess=-4 to +4mmol/L) in the first cord blood analysis performed immediately after birth. Concomitantly, lipid peroxidation byproducts were determined using ultra performance liquid chromatography coupled to mass spectrometry in the same cord blood sample.. A total of 19 controls and 20 cases were recruited. No differences in gestational characteristics were present. However, cases exhibited profound metabolic alterations as compared to controls (Cases vs.. pH=6.90±0.1 vs. 7.33±0.03; base excess=-15±3 vs. -1±2mmol/L), 85% were admitted to the NICU, and 50% developed symptoms of HIE. 8-iso-15(R)-PGF2α (P=0.01) and total isoprostanes (P=0.045) presented statistically significant differences between cases and control groups and correlated with level of HIE.. The 8-iso-15(R)-PGF2α and isoprostanes reflecting oxidative damage are significantly increased in severe postnatal acidemia. Follow up studies with adequate power are necessary to confirm if these biomarkers measured in cord blood serum could be predictive of neonatal encephalopathy.

Topics: Adult; Area Under Curve; Asphyxia Neonatorum; Biomarkers; Case-Control Studies; Dinoprost; Female; Fetal Blood; Humans; Hypoxia-Ischemia, Brain; Isoprostanes; Limit of Detection; Lipid Peroxidation; Male; ROC Curve

Hypoxic ischemic encephalopathy is a serious condition due to inadequate oxygen supply to the brain. Regeneration of neural cells is a critical process for repairing the damaged brain. Nogo has been identified as an inhibitor of neurite outgrowth that is specific to the brain. In the present study, the Nogo-A receptor (NgR) antagonist NEP1-40 was used to study the effects of inhibition of NgR on the regeneration of neural cells and the related Wnt signaling pathway in newborn rats. The investigation focused on the transcription factors regulated in the Wnt signaling pathway during the repair process, together with the proliferation of neural cells. The results indicated that c-Jun and c-Myc were the main transcription factors involved in the Wnt signaling pathway, while neural cell proliferation in the subventricular zone was increased during this process.

Topics: Animals; Animals, Newborn; Cell Proliferation; Dinoprost; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Hypoxia-Ischemia, Brain; JNK Mitogen-Activated Protein Kinases; Ki-67 Antigen; Male; Myelin Proteins; Nerve Regeneration; Neurons; Nogo Proteins; Peptide Fragments; Proto-Oncogene Proteins c-myc; Rats; Rats, Wistar; Up-Regulation; Wnt Signaling Pathway

We have reported that pretreatment with grape seed extract (GSE), a potent antioxidant, is neuroprotective. This study examined whether treatment after injury with GSE is protective. Seven-day-old rat pups had the right carotid artery ligated, and then 2.5 h of 8% oxygen. GSE (50 mg/kg) or vehicle was administered by i.p. initial injection at 5 min to 5 h after reoxygenation, with an additional three doses within 26 h after injury. Brain damage was evaluated by weight deficit of the right hemisphere at 22 d after hypoxia. Treatment at 3 h after reoxygenation reduced brain weight loss from 21.0 +/- 3.3% in vehicle-treated pups (n = 31) to 11.4 +/- 2.8% in treated pups (n = 31, p < 0.05). GSE lowered body temperature, but reduced brain injury even when body temperature was controlled. GSE reduced neurofunctional abnormalities caused by the hypoxia-ischemia (HI). GSE reduced a HI induced increase in 8-isoprostaglandin F2alpha (8-isoPGF2alpha) and reduced an HI-induced increase in the proapoptotic protein c-jun in the brain cortex. GSE up to 3 h after reoxygenation reduces brain injury in rat pups, probably by suppressing lipid peroxidation and the proapoptotic protein c-jun.

Topics: Animals; Animals, Newborn; Antioxidants; Dinoprost; Female; Grape Seed Extract; Hypoxia-Ischemia, Brain; Lipid Peroxidation; Male; Phytotherapy; Plant Extracts; Proanthocyanidins; Proto-Oncogene Proteins c-jun; Rats; Rats, Sprague-Dawley; Seeds; Time Factors; Vitis

Nicotinamide reduces ischemic brain injury in adult rats. Can similar brain protection be seen in newborn animals? Seven-day-old rat pups had the right carotid artery permanently ligated followed by 2.5 h of 8% oxygen. Nicotinamide 250 or 500 mg/kg was administered i.p. 5 min after reoxygenation, with a second dose given at 6 h after the first. Brain damage was evaluated by weight deficit of the right hemisphere at 22 days following hypoxia. Nicotinamide 500 mg/kg reduced brain weight loss from 24.6 +/- 3.6% in vehicle pups (n = 28) to 11.9 +/- 2.6% in the treated pups (n = 29, P < 0.01), but treatment with 250 mg/kg did not affect brain weight. Nicotinamide 500 mg/kg also improved behavior in rotarod performance. Levels of 8-isoprostaglandin F2alpha measured in the cortex by enzyme immune assay 16 h after reoxygenation was 115 +/- 7 pg/g in the shams (n = 6), 175 +/- 17 pg/g in the 500 mg/kg nicotinamide treated (n = 7), and 320 +/- 79 pg/g in the vehicle treated pups (n = 7, P < 0.05 versus sham, P < 0.05 versus nicotinamide). Nicotinamide reduced the increase in caspase-3 activity caused by hypoxic ischemia (P < 0.01). Nicotinamide reduces brain injury in the neonatal rat, possibly by reducing oxidative stress and caspase-3 activity.

Topics: Animals; Animals, Newborn; Apoptosis; Atrophy; Body Temperature; Brain; Brain Infarction; Carotid Stenosis; Caspase 3; Caspases; Dinoprost; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Hypoxia-Ischemia, Brain; Male; Motor Activity; Niacinamide; Organ Size; Oxidative Stress; Rats; Rats, Sprague-Dawley; Treatment Outcome; Vitamin B Complex

Topics: Acidosis; Asphyxia Neonatorum; Dinoprost; Female; Fetal Blood; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Isoprostanes; Lipid Peroxides; Pregnancy; Pregnancy Outcome; Prognosis

Oxygen radicals play a crucial role in brain injury. Grape seed extract is a potent anti-oxidant. Does grape seed extract reduce brain injury in the rat pup? Seven-day-old rat pups had the right carotid arteries permanently ligated followed by 2.5 h of hypoxia (8% oxygen). Grape seed extract, 50 mg/kg, or vehicle was administered by i.p. 5 min prior to hypoxia and 4 h after reoxygenation and twice daily for 1 day. Brain damage was evaluated by weight deficit of the right hemisphere at 22 days following hypoxia and by histopathology. Grape seed extract reduced brain weight loss from 20.0+/-4.4% S.E.M. in vehicle pups (n=21) to 3.1+/-1.6% in treated pups (n=20, P<0.01). Grape seed extract improved the histopathologic brain score in cortex, hippocampus and thalamus (P<0.05 versus vehicle). Concentrations of brain 8-isoprostaglandin F2alpha and thiobarbituric acid reacting substances significantly increased due to hypoxic ischemia. Grape seed extract reduced this increase. Treatment with grape seed extract suppresses lipid peroxidation and reduces hypoxic ischemic brain injury in neonatal rat.

Topics: Animals; Animals, Newborn; Body Temperature; Cerebral Infarction; Dinoprost; Dose-Response Relationship, Drug; Functional Laterality; Hypoxia-Ischemia, Brain; Lipid Peroxidation; Plant Extracts; Rats; Rats, Sprague-Dawley; Seeds; Statistics, Nonparametric; Thiobarbituric Acid Reactive Substances; Time Factors; Vitis

Topics: Asphyxia Neonatorum; Biomarkers; Dinoprost; Disease Progression; Female; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Male; Predictive Value of Tests; Severity of Illness Index; Time Factors