OBJECTIVEThis study examined the changes of regional cerebral oxygen saturation (rSO2) by noninvasive near infrared spectrophotometry in neonates with meconium aspiration syndrome (MAS).

METHODSSeventy-three full neonates with MAS were divided into three groups by respiratory symptoms: asymptomatic group (group 1, n=38), common group (group 2, n=28) and severe group (group 3, n=7). Near infrared spectrophotometry was used to measure the cerebral rSO2 on days 1, 3, 5 and 7 after birth. Thirty healthy full-term newborns served as the Control group.

RESULTSThe cerebral rSO2 of group 1 decreased significantly compared with that of the Control group between days 1 and 3 (P < 0.05). The cerebral rSO2 of group 2 or group 3 was significantly lower than that of group 1 and the Control group on days 1, 3 and 5 (P < 0.05). The MAS patients with mild hypoxic-ischemic encephalopathy (HIE) had significantly higher brain rSO2 levels than those with medium or severe HIE on days 2, 3 and 5 (P < 0.05).

CONCLUSIONSThe cerebral rSO2 decreased in neonates with MAS. The values for rSO2 correlated with the severity of HIE in MAS patients.

Brain ; metabolism ; Female ; Humans ; Hypoxia-Ischemia, Brain ; metabolism ; Infant, Newborn ; Male ; Meconium Aspiration Syndrome ; metabolism ; Oxygen ; metabolism ; Spectroscopy, Near-Infrared

OBJECTIVETo study the effect of rhIGF-1on the mRNA and protein expression of cytochrome C (Cyt-C) and caspase-3 in neonatal rats with hypoxic-ischemic brain damage (HIBD).

METHODSNinety neonatal Sprague-Dawley rats were randomly divided into three groups: normal control, HIBD, and HIBD+rhIGF-1 (rhIGF-1 was given intraperitoneally right after HI). Rat HIBD model was prepared according the Rice-Vannucci method. RT-PCR and Western blot methods were used to measure the mRNA and protein expression of Cyt-C and caspase-3 24, 48 and 72 hrs after HI (n=10 each time point).

RESULTSAt all time points, both Cyt-C mRNA and caspase-3 mRNA expression levels in the HIBD group increased compared with those in the normal control group, and those in the HIBD+rhIGF-1 group also increased compared with that in the normal control group but decreased compared with that in the HIBD group. There were statistical significances among the three groups (P<0.01). At all time points, the changes of both Cyt-C and caspase-3 protein expression in the three groups were similar to those of the mRNA expression: both Cyt-C and caspase-3 protein expression levels increased in the HIBD group compared with those in the normal control group, and those in the HIBD+rhIGF-1 group also increased compared with those in the normal control group but decreased compared with those in the HIBD group. There were statistical significances among the three groups (P<0.01).Pearson correlation analysis showed that mRNA and protein expression of Cyt-C were positively correlated to casapse-3 mRNA and protein expression in the HIBD and the HIBD+rhIGF-1 groups.

CONCLUSIONSrhIGF-1 may inhibit the Cyt-C release and caspase-3 expression, and thus provides neuroprotection against HIBD in neonatal rats.

Animals ; Animals, Newborn ; Brain ; metabolism ; Caspase 3 ; metabolism ; Cytochromes c ; Hypoxia-Ischemia, Brain ; metabolism ; Rats ; Rats, Sprague-Dawley

Brain injury secondary to hypoxia-ischemia (HI) is one of the major causes of neonatal death and severe, long-term neurologic deficits in children. Aside from hypothermia, no established therapies exist. Although the specific mechanisms of hypothermic neuroprotection remain unclear, in part hypothermia suppresses a broad range of injurious factors involved in the both early or primary and late or secondary phases of cell damage and death during the HI injury. In particular, latent (early recovery) phase-a brief period of normal cerebral energetics between resuscitation/reperfusion and the secondary phase of impaired energy metabolism and injury - represents the effective window of opportunity for initiation of therapeutic hypothermia, and ameliorate the later secondary energetic decline, neuronal death and the subsequent neurodevelopmental disability. Randomized controlled studies and systemic reviews have demonstrated that moderate hypothermia (33-35degrees C of core body temperature) using systemic or whole body cooling and selective head cooling, started within 6 hours after birth and protracted for 72 hours, significantly improves survival and reduces neurologic impairment in term and near-term infants with moderate and severe HI encephalopathy. Throughout the world, therapeutic hypothermia is increasingly recommended and we should have the protocols, equipment and training to treat the newborns with moderate and severe HI encephalopathy with therapeutic hypothermia.
Brain ; Brain Injuries ; Child ; Energy Metabolism ; Head ; Humans ; Hypothermia ; Hypoxia-Ischemia, Brain ; Infant ; Infant, Newborn ; Neurologic Manifestations ; Neurons ; Parturition

OBJECTIVETo observe the therapeutic angiogenesis effect of naotai recipe (NR) on local ischemia/reperfusion (I/R) injury of rats by observing signaling pathway of hypoxia-inducible factor-lα (HIF-1α) and vascular endothelial growth factor (VEGF).

METHODSTotally 120 Sprague-Dawley (SD) rats were randomly divided into 4 groups, namely, the normal control group (n =12), the sham-operation group (n =12), the I/R model group (n =48), and the NR group (n =48). Cerebral I/R injury models were established using thread suture method. Rats in the I/R model group and the NR group were sub-divided into 4 sub-groups according to the 1st, 3rd, 5th, and 7th I/R day (n =12). The phenomenon of neovasculization was observed by immunofluorescence staining. The protein and mRNA expression levels of HIF-la, VEGF-A, and VEGFR II receptor were detected by RT-PCR.

RESULTSThere were a large amount of labels for neovasculization in the ischemic area of the NR group. Double-immunofluorescence labeling [vWF (red) and BrdU (green)] was observed in the NR group. Compared with the model group, the HIF-1α protein expression was obviously enhanced on the 1 st day of I/R (P <0.01), and the VEGF protein expression started to enhance on the 3rd day in the NR group (P <0.01). The VEGFR protein expression level was the highest in the NR group on the 5th day of I/R (P <0.01). The protein expression of VEGF and HIF-1α started to decrease on the 7th day of I/R.

CONCLUSIONNR could strengthen angiogenesis after I/R by elevating the expression of HIF-lα and activating HIF-lα/VEGF signaling pathway.

Animals ; Brain Ischemia ; metabolism ; Cerebral Infarction ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Hypoxia-Ischemia, Brain ; metabolism ; Ischemia ; Neovascularization, Pathologic ; Rats, Sprague-Dawley ; Reperfusion Injury ; Signal Transduction ; Vascular Endothelial Growth Factor A ; biosynthesis

Animals ; Animals, Newborn ; Cerebral Cortex ; drug effects ; metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Hypoxia-Ischemia, Brain ; metabolism ; Progesterone ; pharmacology ; Rats ; Rats, Sprague-Dawley

OBJECTIVEHypoxic-ischemic encephalopathy (HIE) is an important cause of morbidity and mortality in the neonates. Early and accurate diagnosis is helpful not only for assessing prognosis but also for making treatment decisions. The aim of this study was to explore the value of early assessment of HIE by applying the diffusion-weighted imaging (DWI) in acute (within 72 hours), subacute or chronic stages of HIE in comparison to conventional magnetic resonance imaging (MRI) in clinical practice.

METHODSImages and clinical charts of fourteen term neonates with clinically diagnosed severe hypoxic-ischemic encephalopathy treated in the NICU from January 2006 to February 2007 were retrospectively reviewed. Inclusion criteria were: term infant (37 approximately 42 weeks) and high clinical suspicion of severe HIE (low Apgar scores, need for resuscitation, metabolic acidosis, acute encephalopathy (eg, hypotonia, coma, seizures). All examinations were performed on a 3.0-T MRI system (Philips Intera Acheva Magnetom Vision) with echo-planar imaging capability with the use of a standard protocol. The imaging protocol for all the patients contained diffuse weighted images (EPI-SE, TR = 2144 ms, TE = 56 ms), T1-weighted images (TR = 389 ms; TE = 15 ms; slice thickness = 4 mm) as well as T2-weighted images (TR = 3035 ms; TE = 100 ms; slice thickness = 4 mm). The studies were first performed within 72 hours of life in these 14 consecutive patients, including both standard T1, T2-weighted image and DWI; follow-up MR studies were performed for 4 patients at the ages of 7 days, for 4 at 14 days, for another 3 at ages of both 21 days and 8 months.

RESULTSFirst inspection (on an average of 48 hours after birth): routine T1, T2-weighted images showed normal images in all patients, while diffusion images showed symmetric high intensity signal in the lateral thalami and posterior limbs of internal capsules (PLIC). Following up: on day 7, routine MRI showed both symmetric T1 prolongation and T2 slightly shortening in lateral thalami, DWI showed abnormal high signal intensity in bilateral basal ganglion (mainly in the back site of lentiform nuclei, putamen) and the cortex around central sulcus, but the previous hyperintensity in lateral thalami and PLIC disappeared. On day 14, routine MRI showed symmetric T1 prolongation, T2 shortening in bilateral thalami, lentiform nuclei and cortex around central sulus. On day 21, routine MRI showed T1 prolongation, T2 shortening in bilateral thalami and basal ganglion while previously obvious PLIC disappeared, whereas DWI showed normal images. Eight months later, deeper cerebral sulus, dilation of ventricles and widening of extracerebral space were shown.

CONCLUSIONDiffusion-weighted imaging has proved more sensitive than conventional MR imaging sequences in detecting acute cerebral infarction in adult subjects. DWI is proposed as a method for early detection of hypoxic-ischemic brain injury. In this study, DWI showed the same focus (lateral thalami and PLIC) and similar extent of the injury in these severe HIE patients in the early stage after birth (in 72 hours). The sites which showed hyperintensive signals in DWI were consistent with the foci in subsequent follow-up by routine MRI. Thus, DWI is supposed to be a technique for early assessment of the extent of hypoxic-ischemic brain injury and the prognosis in clinic. Though DWI is superior to the other imaging modalities in detecting ischemia, diffusion restriction is not necessarily indicative of permanent damage. The abnormal image on DWI may not last long. However, in chronic stage, the follow-up conventional MRI may compensate the inadequacy of DWI.

Brain ; pathology ; Cerebral Cortex ; metabolism ; Cerebral Infarction ; metabolism ; Diffusion ; Humans ; Hypoxia-Ischemia, Brain ; metabolism ; Infant ; Infant, Newborn ; Magnetic Resonance Imaging ; methods ; Stroke ; metabolism

Acupuncture Therapy ; Animals ; Animals, Newborn ; Brain ; metabolism ; Hypoxia-Ischemia, Brain ; metabolism ; therapy ; Malondialdehyde ; metabolism ; Nitric Oxide ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the change in regulation of cerebral blood flow (CBF) and cerebral metabolism rate (CMR) during selective head cooling (SHC) in newborn piglets.

METHODSSixteen newborn piglets, aged 5 approximately 7 days, were randomly assigned to one of the following three groups: SHC in normal piglets (n = 4), SHC after hypoxia-ischemia HI (n = 6) and normal temperature after HI (n = 6). Nasopharyngeal temperature was respectively reduced to 35 degrees C and then 32 degrees C in SHC group. HI was induced by using temporary occlusion of the bilateral carotid arteries and mechanical ventilation with low concentration of oxygen (6%) for 30 minutes. CBF was measured with color microspheres method. Mixed venous blood and arterial sample were collected at the same time from superior sagittal sinus and forelimb artery respectively for blood gas analysis, blood glucose and lactate measurement. Cerebral oxygenation metabolism rate (CMRO(2)), cerebral glucose metabolism rate (CMR(Glu)) and cerebral lactate production (CLP) were calculated.

RESULTSIn normal piglets, CBF, CMRO(2) and CMR(Glu) were significantly decreased at 35 degrees C and 32 degrees C respectively, while CLP did not change. When nasopharyngeal temperature decreased to 35 degrees C, The ratios of CBF/CMRO(2), CBF/CMR(Glu) and CBF/CLP did not significantly change, coupling of CBF and CMR was maintained. While nasopharyngeal temperature decreased to 32 degrees C, the ratios of CBF/CMR(Glu) and CBF/CLP significantly decreased. Maintained newborn piglets normal temperature after HI, the CBF and CMRO(2) were significantly reduced, while CMR(Glu) and CLP were markedly increased. The ratio of CBF/CMRO(2) increased, CBF/CMR(Glu) and CBF/CLP decreased. Uncoupling of CBF and CMR was observed. During SHC after HI, the same decrease was observed in CBF and CMR(Glu) and CLP was markedly reduced. The ratio of CBF/CMRO(2), CBF/CMR(Glu) and CBF/CLP were restored at 35 degrees C and 32 degrees C as compared to the same time point in normal temperature, respectively.

CONCLUSIONCBF and CMR decreased in normal piglets during SHC and coupling of CBF and CMR was maintained. After HI, CBF was reduced and the disturbance of cerebral oxygenation metabolism occurred. CBF and CMR was uncoupled. SHC after HI can improve CMR and correct uncoupling of CBF and CMR.

Animals ; Animals, Newborn ; metabolism ; Blood Glucose ; Brain ; blood supply ; metabolism ; Cerebrovascular Circulation ; Cold Temperature ; Hypothermia, Induced ; Hypoxia-Ischemia, Brain ; metabolism ; Lactic Acid ; blood ; Oxygen Consumption ; Swine ; metabolism

We have previously shown that cycloheximide significantly inhibited apoptosis, and reduced ensuing cerebral infarction in a newborn rat model of cerebral hypoxiaischemia. This study was performed to determine the therapeutic window for cycloheximide therapy. Seven day-old newborn rat pups were subjected to 100 min of 8% oxygen following a unilateral carotid artery ligation, and cycloheximide was given at 0, 6, 12 and 24 hr after hypoxia-ischemia (HI). Apoptosis or necrosis was identified by performing flow cytometry with a combination of fluorescinated annexin V and propidium iodide, and the extent of cerebral infarction was evaluated with triphenyl tetrazolium chloride (TTC) at 48 hr and 72 hr after HI, respectively. With cycloheximide treatment at 0 hr after HI, both apoptotic and necrotic cells by flow cytometry were significantly reduced, only necrotic cells were significantly reduced at 6 and 12 hr, and no protective effect was seen if administration was delayed until 24 hr after HI compared to the HI control group. Infarct volume, measured by TTC, was significantly reduced by 92% and 61% when cycloheximide was given at 0 or 6 hr after HI respectively; however, there was an insignificant trend in infarct reduction if cycloheximide was administered 12 hr after HI, and no protective effect was observed when administration was delayed until 24 hr after HI. In summary, cycloheximide was neuroprotective when given within 6 hr after HI in the developing newborn rat brain.
Rats, Sprague-Dawley ; Rats ; Protein Synthesis Inhibitors/therapeutic use ; Oxygen/metabolism ; Neuroprotective Agents/*therapeutic use ; Necrosis ; Hypoxia-Ischemia, Brain/*drug therapy ; Hypoxia, Brain ; Humans ; Flow Cytometry ; Cycloheximide/*therapeutic use ; Brain Ischemia ; Apoptosis ; Animals, Newborn ; Animals

Hypoxic-ischemic encephalopathy (HIE) in neonates is the brain injury caused by perinatal asphyxia or hypoxia and is a major cause of death in neonates and nervous system dysfunction in infants and young children. Although to a certain degree, mild hypothermia therapy reduces the mortality of infants with moderate to severe HIE, it cannot achieve the expected improvements in nervous system dysfunction. Hence, it is of vital importance to search for effective therapeutic methods for HIE. The search for more therapies and better preventive measures based on the pathogenesis of HIE has resulted in much research. As an important link in the course of HIE, energy failure greatly affects the development and progression of HIE. This article reviews the research advances in the treatment and prevention of energy failure in the course of HIE.
Energy Metabolism ; Humans ; Hypothermia, Induced ; Hypoxia-Ischemia, Brain ; prevention & control ; therapy ; Infant, Newborn ; Infant, Newborn, Diseases ; prevention & control