It has since long been demonstrated that perinatal asphyxia in pigs can result in perinatal mortality, decreased viability/vitality at birth and reduced survival rates until 10 days of age. In human perinatology much interest is presently focussed on strategies to prevent adverse outcome arising from birth asphyxia. Given the rather high perinatal and postnatal losses in the pig industry, it is very interesting to explore rescue strategies to reduce adverse effects of postischemic organ damage caused by perinatal asphyxia also in newborn piglets.
The aim of this study was to determine the effects of postnatal treatment of piglets with 2-IminoBiotin (2-IB), a selective inhibitor of neuronal and inducible NitricOxideSynthase (nNOS and iNOS), under farm conditions on postnatal growth rates, morbidity and mortality.
In total 81 piglets from 15 litters were used. Immediately after birth, blood was collected from the umbilical artery and piglets were alternately assigned to either a control (saline) or drug (2-IB; 0.18 mg/kg bodyweight every 4 h during 24 h) group. Administration of control or drug started with an intravenous injection in the umbilical vein immediately after birth, followed by 6 intraperitoneal injections at 4 h intervals, starting 4 h after the intravenous injection. Piglets were checked for growth, morbidity and mortality until the experiment was finished (average age: 44 days).
Postnatal treatment with 2-IB resulted in significantly increased growth rates at 10 days of age (P = 0.02) (165 g/day compared to 140 g/day in controls), independently of health status and birth weight. At weaning 2-IB treated piglets tended to show higher growth rates (P = 0.06). Growth rates at the end of the experiment, morbidity and mortality were not affected by treatment.
It is hypothesized that 2-IB reduces the rather limited, nearly ‘physiological’ harmful effects occurring in the gastrointestinal tract, resulting from a short period of hypoxia-ischemia experienced during birth. This might explain the significantly increased growth rates at 10 days of life in 2-IB treated piglets. Selective inhibition of nNOS and iNOS might also result in increased availability of l-arginine for protein synthesis in newborns resulting in higher postnatal growth rates. However these issues need further investigations.
In conclusion, this study showed a positive effect of immediate postpartum administration of 2-IB during the first day after birth on growth rates up to 10 days of age. Furthermore, no negative effects of 2-IB treatment on piglet health and survival were found. 相似文献
Apoptosis is one of the most important causes, which results in the central neuronal system complication in hypoxic-ischemic brain damage (HIBD). Apoptosis occurs in the developing brain more than in the developed brain. Apoptosis can last several weeks and may be inverted its pathology by appropriate therapy. Caspase inhibitor, neurotrophic factors, anti-apoptosis gene Bcl-2, mild hypothermia,and early intervention play important roles in promoting neuronal cell survival and preventing from apoptosis through different mechanisms. It may be a new way for rehabilitation of HIBD. 相似文献
AIM： To study the expression of p-p38 MAPK in partial cerebral tissues after hypoxic-ischemic brain damage (HIBD) in the neonatal adenosine A2A receptor knockout (A2AR-/-) mice. METHODS：Base on the modified Rice method, the model of HIBD was established. The total 64 C57/BL6 neonatal mice (7 days old) of A2AR-/-(KO) and corresponding wild type (A2AR+/+, WT) were randomized into sham-operated group and model group. The mice in model group were divided into 3 subgroups： 1 d after HIBD, 3 d after HIBD and 7 d after HIBD (n=8 for each group). The cortex and hippocampal CA1 region were used as the study areas. The neuronal apoptosis was detected using TUNEL assay combined with Nissl staining. The expression of p-p38 MAPK and activated caspase-3 was determined by the method of immunohistochemistry. The KO mice and WT mice were also taken from sham-operated group (SKO and SWT, n=10) and model group (MKO and MWT, n=30) 1 d after HIBD to assess the early neurological behavior. RESULTS：The apoptotic neurons, activated caspase-3 and p-p38 MAPK increased after HIBD and peaked at 1 d after HIBD in the cortex and the hippocampal CA1 region. The apoptotic neurons and the expression of activated caspase-3 in KO mice were significantly higher than those in WT mice at the same time point after HIBD. The expression level of p-p38 MAPK in KO mice were significantly higher than that in WT mice at 1 d and 3 d after HIBD. The expression of activated caspase-3 was positively correlated with the expression of p-p38 MAPK in neonatal mice after HIBD (in the cortex：r=0.957, P<0.01; in the hippocampal CA1 region： r=0.939, P<0.01). CONCLUSION：p-p38 MAPK might be involved in the aggravated neuron apoptosis and brain damage induced by A2AR knockout after neonatal HIBO. 相似文献
AIM: To establish intrauterine hypoxic-ischemic brain damage (HIBD) model in near term fetal rabbits at 29 d gestation age for the investigation of the pathogenesis and treatment of newborn HIBD. METHODS: Twenty-four pregnant New Zealand white rabbits at 29th gestational day were chosen for this project. Under combined general anesthesia and spinal anesthesia, a 4F Fogarty arterial embolectomy catheter was introduced into the left femoral artery. The blood supply of uterus in experiment group was blocked by inflating the catheter balloon with 0.3 mL saline for 20 min, 25 min, 28 min, 30 min and 40 min (n=4 for each experimental time group). The catheter balloon was not inflated in control group (n=4). All pregnant rabbits were subject to cesarean section 24 h after the experimental procedure to induce hypoxia-ischemia to the fetus. The general conditions of the newborn rabbits were recorded, and the neurobehavioral damage and histology of the brain tissue were assessed. RESULTS: During the entire procedure, the pregnant rabbits had stable vital signs, no hypoxia happened,and had a good tolerance to the anesthesia program. When the balloon was inflated, the pulses of right femoral artery disappeared and the right leg blood pressure became non-detectable in experimental groups. In contrast, no fluctuation of the right leg blood pressure in control group (P>0.05) was observed. Intrauterine hypoxia-ischemia caused neonatal and fetal rabbit death, neurobehavioral damage and brain cell death. When the balloon was inflated for 20 min, all fetal rabbits were alive and had no obvious neurologic damage. For 25~28 min, the stillbirth rates were 12.9% and 40.6%, respectively, while the live neonatal rabbits manifested neurobehavioral damage, edema neural cells, activated microglia cells and apoptotic brain cells. When blocking time beyond 30 min, above 80% fetal rabbits died. CONCLUSION: Continuous blockage of uterine blood supply in pregnant rabbits causes neonatal rabbit death, neurobehavioral damage and brain cell death. Different blocking time arouses different levels of brain damage. Continuous blockage of uterine blood supply for 25-28 min can establish fetal generalize hypoxic-ischemic brain damage rabbit model, which is a good animal model for the investigation of newborn HIBD. 相似文献
AIM: To study the effect of moderate hypothermia on immature rats with hypoxic-ischimic brain damage (HIBD). METHODS: The rats with HIBD were divided into normothermic recovered group (IN) and moderate-hypothermic recovered group (IH). Sham-operated rat pups were normothermic control group (NC) and moderate-hypothermic control group (HC). 0, 2, 6, 24, 48, 72 h after the end of hypoxic-ischemic (HI) insult, the brain was homogenized for measuring glucose and ATP, brain mitochondria was extracted for SDH activity, complex II activity and the capacity of ATP synthesization. RESULTS: In IN group, the brain glucose was significantly lower at 0 h, and recovered as normal at 2 h. The brain ATP and brain-mitochondrial SDH activities were firstly decreased at 2 h, 6 h and then recovered gradually, it was at it's peak value at 72 h. Brain-mitochondrial complex II activity and the capacity of ATP synthesis were recovered at 2 h, but they decreased again at 6 h and came to normal level at 72 h. In moderate-hypothermic group, all the indexes were significantly higher at all the time point than that in IN groups. CONCLUSION: Moderate hypothermia inhibits the decrease in the mitochondrial SDH activity, mitochondrial complex II activity and the capacity of ATP synthesis, increases the brain ATP concentration, improves the energy metabolism, and then protects the brain tissue. 相似文献
AIM: To investigate the effects of diazoxide, an ATP-sensitive K+ channel opener on the μ-calpain activation, c-Fos and c-Jun expression in neonatal hypoxic-ischemic rat brain. METHODS: The animal model of hypoxic-ischemic brain injury (HIBI) was made in the 7-day-old SD rats. Diazoxide was injected into the left lateral ventricle prior or post hypoxic-ischemia (HI) insults. Western blot was applied to detect the integrated density (ID) of the nuclear c-Fos and c-Jun at 4h, and the cleavage of cytosolic μ-calpain at 24 h after HI insults. RESULTS: Low c-Fos and c-Jun expressions from cortical and hippocampal samples were observed in the two diazoxide groups, and significant differences in their expressions were found by comparison with the HI controls (P<0.05 respectively). Furthermore, the administration of diazoxide prior or post HI insults inhibited the cleavage of μ-calpain. CONCLUSION: Diazoxide down-regulated the expression of c-Fos and c-Jun, and inhibited the activation of μ-calpain may contribute to the neuroprotection from as well as therapeutical effects on HIBI. 相似文献
