The mechanisms leading to delayed neuronal death after asphyxial cardiac arrest (ACA) in the developing brain are unknown. This study aimed at investigating the possible role of microglial activation in neuronal death in developing brain after ACA. Postnatal day-17 rats were subjected to 9 mins of ACA followed by resuscitation. Rats were randomized to treatment with minocycline, (90 mg/kg, intraperitoneally (i.p.)) or vehicle (saline, i.p.) at 1 h after return of spontaneous circulation. Thereafter, minocycline (22.5 mg/kg, i.p.) was administrated every 12 h until sacrifice. Microglial activation (evaluated by immunohistochemistry using ionized calcium-binding adapter molecule-1 (Iba1) antibody) coincided with DNA fragmentation and neurodegeneration in CA1 hippocampus and cortex (assessed by deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL), Fluoro-Jade-B and Nissl stain). Minocycline significantly decreased both the microglial response and neuronal degeneration compared with the vehicle. Asphyxial CA significantly enhanced proinflammatory cytokine and chemokine levels in hippocampus versus control (assessed by multiplex bead array assay), specifically tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-1α (MIP-1α), regulated upon activation, normal T-cell expressed and secreted (RANTES), and growth-related oncogene (GRO-KC) (P<0.05). Minocycline attenuated ACA-induced increases in MIP-1α and RANTES (P<0.05). These data show that microglial activation and cytokine production are increased in immature brain after ACA. The beneficial effect of minocycline suggests an important role for microglia in selective neuronal death after pediatric ACA, and a possible therapeutic target. 相似文献
Cerebral palsy (CP) is a group of movement and posture disorders attributed to insults in the developing brain. In rats, CP-like motor deficits can be induced by early hind-limb sensorimotor restriction (SR; from postnatal days P2 to P28), associated or otherwise with perinatal anoxia (PA; on P0 and P1). In this study, we address the question of whether PA, early SR or a combination of both produces alterations to sensorimotor development. Developmental milestones (surface righting, cliff aversion, stability on an inclined surface, proprioceptive placing, auditory startle, eye opening) were assessed daily from P3 to P14. Motor skills (horizontal ladder and beam walking) were evaluated weekly (from P31 to P52). In addition, on P52, the thickness of the somatosensory (S1) and cerebellar cortices, and corpus callosum were measured, and the neuronal and glial cell numbers in S1 were counted. SR (with or without PA) significantly delayed the stability on an inclined surface and hastened the appearance of the placing reflex and impaired motor skills. No significant differences were found in the thickness measurements between the groups. Quantitative histology of S1 showed that PA, either alone or associated with SR, increased the number of glial cells, while SR alone reduced neuronal cell numbers. Finally, the combination of PA and SR increased the size of neuronal somata. We conclude that SR impairs the achievement of developmental milestones and motor skills. Moreover, both SR and PA induce histological alterations in the S1 cortex, which may contribute to sensorimotor deficits. 相似文献
Abstract. The effect of induction of labour on the foetus and the newborn was investigated in a prospective randomized study. 41 neonates were studied after induction at full term by amniotomy and intravenous oxytocin infusion. The infusion rate was regulated by the intraamniotic pressure using the Cardiff infusion pump system. 39 neonates served as controls where the labour started spontaneously followed by amniotomy. In both groups foetal heart rate monitoring and intraamniotic pressure recordings were performed. There were no differences in Apgar score and pH in cord blood between the groups. The newborns were evaluated the first and the fifth day of life with the Brazelton Neonatal Behavioral Assessment Scale and with a modified Prechtl neurological examination. There were no differences in behaviour and neurological state between the two groups. However, within the groups there were significant differences between the first and the fifth day concerning both neonatal behaviour and neurological state. 相似文献
Perinatal asphyxia is a concern for public health and may promote subtle neuropsychiatric disorders. Anoxic insults to neonatal rats cause long-lasting neurobehavioral deficits. In the present study, we focussed on changes in emotional behaviors as a consequence of neonatal asphyxia in Wistar rats. Newborn pups (24 h after birth) underwent a single 30-min exposure to a 100% N2 atmosphere (or air). The offspring was tested for a) locomotor and exploratory activity with or without a d-amphetamine challenge (0, 1, or 2 mg/kg) on postnatal day (pnd) 15; b) social interactions and novelty seeking during adolescence; c) levels of the brain-derived neurotrophic factor (BDNF). In the open-field test (pnd 15), N2-exposed pups injected with the high (2 mg/kg) amphetamine dose exhibited reduced levels of locomotor hyperactivity, and a more marked involvement in stereotyped behaviors. Individual differences emerged in the locomotor response to the novelty-seeking test: two subgroups of rats (separated on the basis of the median value) showed either arousal/attraction or avoidance/inhibition in response to free-choice novelty. The N2-exposed group showed a more marked novelty-induced avoidance and inhibition. Time devoted to allogrooming and play-soliciting behaviors was reduced, whereas object exploration was increased. Levels of BDNF were reduced in the striatum of N2-exposed rats, suggesting poorer synaptic performance of dopamine pathways. In conclusion, these findings suggest an increased risk of developing social withdrawal, neophobia and behavioral stereotypies (common symptoms found in schizophrenia and autism) as a consequence of neonatal asphyxia in preterm humans. 相似文献
Measurement of the end-tidal partial pressure of carbon dioxide (PETCO2) during cardiac arrest has been shown to reflect the blood flow being generated by external means and to prognosticate outcome. In the present issue of Critical Care, Grmec and colleagues compared the initial and subsequent PETCO2 in patients who had cardiac arrest precipitated by either asphyxia or ventricular arrhythmia. A much higher PETCO2 was found immediately after intubation in instances of asphyxial arrest. Yet, after 1 min of closed-chest resuscitation, both groups had essentially the same PETCO2, with higher levels in patients who eventually regained spontaneous circulation. The Grmec and colleagues' study serves to remind us that capnography can be used during cardiac resuscitation to assess the mechanism of arrest and to help optimize the forward blood flow generated by external means. 相似文献
Basal ganglia abnormalities on magnetic resonance imaging predict neurodevelopmental impairment in newborns with perinatal depression. We determined the value of a clinical encephalopathy score as a predictor of abnormal magnetic resonance imaging results in newborns with perinatal depression.
We assigned a neonatal encephalopathy score to 101 newborns. The encephalopathy score, based on alertness, feeding, tone, respiratory status, reflexes, and seizure activity, was assigned once daily. The maximum score from the first 3 days of life was compared with abnormal magnetic resonance imaging results present globally or solely in the basal ganglia.
Eighty-one percent of patients manifested abnormalities on any magnetic resonance imaging sequence, and 37% manifested abnormalities in the basal ganglia alone. The encephalopathy score correlated well with magnetic resonance imaging abnormalities in the basal ganglia (Spearman Rho = 0.335, P < 0.0001). Newborns with mild and severe encephalopathy had likelihood ratios of 0.41 and 7.4, respectively, for abnormal basal ganglia magnetic resonance imaging results. Newborns with moderate encephalopathy (composing 47% of the cohort) manifested basal ganglia abnormalities with a likelihood ratio of 0.785.
Severe clinical encephalopathy correlates with abnormal basal ganglia magnetic resonance imaging results, and mild encephalopathy correlates with a normal magnetic resonance imaging result. However, standard clinical criteria do not alter the prior risk of abnormal basal ganglia magnetic resonance imaging results for newborns with moderate encephalopathy. 相似文献
A new field of clinical and scientific interest has recently developed based on the discovery that the hematopoietic cytokine erythropoietin (Epo) has important non-hematopoietic functions in the brain and other organs, particularly during development. The biological effects of Epo in the central nervous system (CNS) involve activation of its specific receptor and corresponding signal transduction pathways. Epo receptor expression is abundant in the developing mammalian brain, and decreases as term approaches. Epo has been identified as a neurotrophic and neuroprotective agent in a wide variety of experimental paradigms, from neuronal cell culture to in vivo models of brain injury. Several mechanisms by which Epo produces neuroprotection are recognized. Epo (i) decreases glutamate toxicity, (ii) induces the generation of neuronal anti-apoptotic factors, (iii) reduces inflammation, (iv) decreases nitric oxide-mediated injury, and (v) has direct antioxidant effects. Conclusion : Collectively, the evidence suggests that Epo may provide a new approach to the treatment of a variety of CNS disorders in adults and children, especially as a possible therapy for perinatal asphyxia. This review summarizes the current knowledge on the neurotrophic and neuroprotective functions of Epo in the developing and injured brain. 相似文献
A study concerning the relationship between neonatal neurological abnormality and 3 parameters of pre- and perinatal condition in a birth cohort of 1507 infants was replicated in a second cohort of 1655 infants. The 3 parameters chosen were preterm birth, intrauterine growth retardation and neonatal acidemia. The neurological examination in the second cohort was carried out by other examiners than in the first cohort. The incidence of neurological abnormality was again found to be raised in all 3 categories and again least in the acidemic subgroup. Also the finding could be confirmed that only in about half of the neurologically abnormal infants could the 3 parameters have exerted any effect at all, which implies the necessity of further analysis.This replication study shows that neurological examination in the newborn period is a reliable tool for the evaluation of the condition of infants with respect to their pre- and perinatal history. 相似文献