Humans ; Hypoxia-Ischemia, Brain ; pathology ; Infant, Newborn ; Magnetic Resonance Imaging

Neuroinflammation is a key contributor to the pathogenic cascades induced by hypoxic-ischemic (HI) insult in the neonatal brain. AD-16 is a novel anti-inflammatory compound, recently found to exert potent inhibition of the lipopolysaccharide-induced production of pro-inflammatory and neurotoxic mediators. In this study, we evaluated the effect of AD-16 on primary astrocytes and neurons under oxygen-glucose deprivation (OGD) in vitro and in mice with neonatal HI brain injury in vivo. We demonstrated that AD-16 protected against OGD-induced astrocytic and neuronal cell injury. Single dose post-treatment with AD-16 (1 mg/kg) improved the neurobehavioral outcome and reduced the infarct volume with a therapeutic window of up to 6 h. Chronic administration reduced the mortality rate and preserved whole-brain morphology following neonatal HI. The in vitro and in vivo effects suggest that AD-16 offers promising therapeutic efficacy in attenuating the progression of HI brain injury and protecting against the associated mortality and morbidity.
Animals ; Animals, Newborn ; Astrocytes/pathology* ; Brain/pathology* ; Brain Injuries/pathology* ; Glucose ; Hypoxia ; Hypoxia-Ischemia, Brain/drug therapy* ; Mice ; Neuroinflammatory Diseases ; Neuroprotective Agents/therapeutic use* ; Oxygen/therapeutic use*

BACKGROUNDMild hypoxic-ischemic encephalopathy (HIE) injury is becoming the major type in neonatal brain diseases. The aim of this study was to assess brain maturation in mild HIE neonatal brains using total maturation score (TMS) based on conventional magnetic resonance imaging (MRI).

METHODSTotally, 45 neonates with clinically mild HIE and 45 matched control neonates were enrolled. Gestated age, birth weight, age after birth and postmenstrual age at magnetic resonance (MR) scan were homogenous in the two groups. According to MR findings, mild HIE neonates were divided into three subgroups: Pattern I, neonates with normal MR appearance; Pattern II, preterm neonates with abnormal MR appearance; Pattern III, full-term neonates with abnormal MR appearance. TMS and its parameters, progressive myelination (M), cortical infolding (C), involution of germinal matrix tissue (G), and glial cell migration bands (B), were employed to assess brain maturation and compare difference between HIE and control groups.

RESULTSThe mean of TMS was significantly lower in mild HIE group than it in the control group (mean ± standard deviation [SD] 11.62 ± 1.53 vs. 12.36 ± 1.26, P < 0.001). In four parameters of TMS scores, the M and C scores were significantly lower in mild HIE group. Of the three patterns of mild HIE, Pattern I (10 cases) showed no significant difference of TMS compared with control neonates, while Pattern II (22 cases), III (13 cases) all had significantly decreased TMS than control neonates (mean ± SD 10.56 ± 0.93 vs. 11.48 ± 0.55, P < 0.05; 12.59 ± 1.28 vs. 13.25 ± 1.29, P < 0.05). It was M, C, and GM scores that significantly decreased in Pattern II, while for Pattern III, only C score significantly decreased.

CONCLUSIONSThe TMS system, based on conventional MRI, is an effective method to detect delayed brain maturation in clinically mild HIE. The conventional MRI can reveal the different retardations in subtle structures and development processes among the different patterns of mild HIE.

Brain ; pathology ; Female ; Humans ; Hypoxia-Ischemia, Brain ; diagnosis ; Infant, Newborn ; Magnetic Resonance Imaging ; methods ; Male

OBJECTIVETo elucidate that diffusion weighted imaging (DWI) can be used to predict the injured regions of neonatal brain with hypoxic-ischemic encephalopathy (HIE) in the early phase of injury, and to measure the apparent diffusion coefficient (ADC) values in the multiple regions of the brain.

METHODThe participants in this study were twenty-six infants with HIE from neonatology ward hospitalized between July 2006 and July 2009. Nineteen patients had severe HIE, and seven had moderate HIE. DWI and conventional magnetic resonance imaging (MRI) were performed for each case within the first 72 hrs. The ADC values of eight regions of interest (ROIs) were measured in ten cases with severe HIE (ADC values group). ROIs included posterior limb of internal capsule (PLIC), ventrolateral thalami, basal ganglia, perirolandic cortex, occipital cortex, centrum semiovale, brainstem, and frontal white matter. Twelve neonates were enrolled as the control subjects.

RESULTSDuring the first 72 hrs, the conventional MRI of 26 patients showed subarachnoid hemorrhage in 5, subdural hemorrhage in 2, and mild high signal intensity in the cortex of only one patient. In the 19 cases with severe HIE, abnormal signal intensities were seen in ventrolateral thalami and perirolandic cortex of 17 patients (89%), and the remaining 2 infants showed abnormal cortex and subcortical white matter. In 7 cases with moderate HIE, 4 had abnormal signal intensity in the cortex and subcortical white matter, 2 had abnormal periventricular white matter, and only one showed abnormal signal intensity in the ventrolateral thalami and perirolandic cortex. In the ADC values group, the average ADC values of posterior limb of internal capsule (PLIC), ventrolateral thalami, basal ganglia, perirolandic cortex, occipital cortex, centrum semiovale, brainstem, and frontal white matter respectively were 0.68 (0.56 - 0.88), 0.73 ± 0.13, 0.67 ± 0.11, 0.78 ± 0.22, 0.90 ± 0.16, 0.87 ± 0.21, 0.73 ± 0.19, 1.32 ± 0.22 × 10(-3) mm(2)/S. In the control group, the average ADC values of posterior limb of internal capsule (PLIC), ventrolateral thalami, basal ganglia, perirolandic cortex, occipital cortex, centrum semiovale, brainstem, and frontal white matter respectively were 0.96 (0.95 - 1.02), 1.02 ± 0.90, 1.15 ± 0.99, 1.08 ± 0.07, 1.09 ± 0.08, 1.39 ± 0.20, 0.96 ± 0.05, 1.58 ± 0.18× 10(-3) mm(2)/S. There was statistically significant difference in the average ADC values between each of 8 ROIs of infants with HIE and healthy neonates (P < 0.01).

CONCLUSIONIn the first days after birth, the major injured regions of severe HIE were ventrolateral thalami and perirolandic cortex, the minor injured regions were cortex and subcortical white matter. Multiple regions of moderate HIE were injured, including cortex with subcortical white matter, periventricular white matter, and ventrolateral thalami with perirolandic cortex. The ADC values of the regions with abnormal signal intensity decreased, also some regions with the normal signal intensity.

Brain ; pathology ; Diffusion Magnetic Resonance Imaging ; methods ; Female ; Humans ; Hypoxia-Ischemia, Brain ; diagnosis ; Infant, Newborn ; Male

OBJECTIVETo understand the clinical characteristics of hypoxic-ischemic encephalopathy (HIE) in full-term infants and to explore the value of magnetic resonance imaging (MRI) for the early prediction of HIE prognosis.

METHODSThe medical data, including histories, clinical manifestations, MRI findings and follow-up outcomes, of 348 full-term infants with HIE between January 2001 and December 2005 were retrospectively reviewed.

RESULTSHIE patients (348 cases) accounted for 8.25% of in-patients (4220 cases) over the five years. The etiology of HIE mainly attributed to birth asphyxia (76.2%), consisting of mild asphyxia (59.2%) and severe asphyxia (40.8%). A poor outcome was confirmed in 10.1% of these patients, including 27.3% in severe HIE, 10.0% in moderate HIE and 1.5% in mild HIE cases. All of patients whose MRI showed diffusion intraparenchymal hemorrhages and cerebral infarctions had poor outcomes. Fourteen (87.5%) out of the 16 cases with basal ganglia and thalamic or internal capsule injury and 9 (81.8%) out of the 11 cases with cytotoxic brain edema diagnosed by diffusion weighted imaging had poor outcomes.

CONCLUSIONSHIE is one of common diseases in newborn infants. The etiology of neonatal HIE mainly attributed to birth asphyxia, mild asphyxia accounting for a greater proportion. MRI findings can be helpful for the early prediction of HIE prognosis.

Brain ; pathology ; Humans ; Hypoxia-Ischemia, Brain ; diagnosis ; etiology ; pathology ; Infant, Newborn ; Magnetic Resonance Imaging ; methods ; Prognosis ; Retrospective Studies

Brain ; pathology ; Cerebrovascular Circulation ; Humans ; Hypoxia-Ischemia, Brain ; diagnosis ; pathology ; prevention & control ; Infant, Newborn ; Infant, Premature ; Magnetic Resonance Imaging

OBJECTIVEThis study aimed to prepare a hypoxic brain damage model in the neonatal rat using a new approach, 0% oxygen exposure, and to explore the reliability and advantages of the new model.

METHODSSeven-day-old Wistar rats were randomly exposed to either 7 minutes of 0% oxygen, to the conventional Rice-Vannucci method (ischemia + 2 hrs hypoxia exposure), or to left common carotid artery ligation (ischemia). Rat pups which were not subjected to any hypoxia-ischemia treatment were used as the control group. Brain water content and neuronal apoptosis were measured. Neurofunctional assessment was performed. Brain pathological changes were observed using hematoxylin and eosin staining.

RESULTSThe water content (88.96+/-0.29%) and apoptosis of neurons (31.52+/-5.45%) of the left brain in the 0% oxygen group were significantly higher than those of the ischemic and the control groups (P<0.01), and similar to those in the Rice-Vannucci group. The water content (88.68+/-0.24%) and apoptosis of neurons (30.85+/-5.38%) of the right brain in the 0% oxygen group were significantly higher than those of the Rice-Vannucci, the ischemic and the control groups (P<0.01). Both side brains of the 0% oxygen group showed pathological injuries, but only left brain of the Rice-Vannucci group had pathological changes. No pathological abnormalities were seen in the ischemic and the control groups. Significant neurofunctional impairments were found in the 0% oxygen and the Rice-Vannucci groups.

CONCLUSIONSA hypoxic brain damage model of neonatal rat was successfully prepared using 7 minutes 0% oxygen exposure. The new approach appears to be simple and reliable.

Animals ; Animals, Newborn ; Apoptosis ; Brain ; pathology ; Disease Models, Animal ; Female ; Hypoxia, Brain ; pathology ; physiopathology ; Male ; Rats ; Rats, Wistar

OBJECTIVETo investigate the clinical and imaging characteristics of acute hypoxic-ischemic brain injury (HIBI) due to perinatal sentinel events in neonates.

METHODSForty-six neonates with acute HIBI who were admitted between January 2004 and May 2013, and who had a history of major cardiopulmonary resuscitation, were enrolled in the study. They were classified into full-term and preterm infants to analyze the clinical and imaging characteristics.

RESULTSAmong full-term infants, the incidence rates of white matter injury, cortical injury, basal ganglia /thalamic injury, and brain stem injury were 95%, 90%, 75%, and 65%, respectively; among preterm infants, the incidence rates of white matter injury, cortical injury, basal ganglia/thalamic injury, and brain stem injury were 73%, 23%, 19%, and 15%, respectively. Compared with full-term infants, preterm infants had a significantly lower incidence of gray matter injury in the cortex, basal ganglia/thalamus, and brain stem (P<0.05). About 46% of all subjects had multiple organ dysfunction. The 20 full-term infants with HIBI had typical clinical manifestations; 19 (95%) of them had moderate or severe neonatal encephalopathy, with mixed lesions on magnetic resonance imaging (MRI), and moderate or severe basal ganglia/thalamic injury was found in 68% of these patients. Multiple organ dysfunction, various abnormal neurological manifestations, and arterial blood pH less than 7.1 were closely related to moderate or severe brain injury.

CONCLUSIONSWhite matter injury is the most common type of HIBI. Gray matter injury can be found in preterm infants, but the incidence is lower than that in full-term infants. Moderate or severe neonatal encephalopathy is mainly manifested as basal ganglia/thalamic injury on MRI. Evaluation of multiple organ dysfunction and abnormal neurological manifestations and early blood gas analysis are very important for the diagnosis of neonatal HIBI.

Acute Disease ; Brain ; pathology ; Female ; Humans ; Hypoxia-Ischemia, Brain ; diagnosis ; etiology ; pathology ; Infant, Newborn ; Magnetic Resonance Imaging ; Male

In recent years, magnetic resonance imaging (MRI) has been widely used in evaluating neonatal brain development, diagnosing neonatal brain injury, and predicting neurodevelopmental prognosis. Based on current research evidence and clinical experience in China and overseas, the Neonatologist Society of Chinese Medical Doctor Association has developed a consensus on the indications and standardized clinical process of neonatal brain MRI. The consensus has the following main points. (1) Brain MRI should be performed for neonates suspected of hypoxic-ischemic encephalopathy, intracranial infection, stroke and unexplained convulsions; brain MRI is not considered a routine in the management of preterm infants, but it should be performed for further evaluation when cranial ultrasound finds evidence of brain injury; as for extremely preterm or extremely low birth weight infants without abnormal ultrasound findings, it is recommended that they should undergo MRI examination at term equivalent age once. (2) Neonates should undergo MRI examination in a non-sedated state if possible. (3) During MRI examination, vital signs should be closely monitored to ensure safety; the necessity of MRI examination should be strictly evaluated for critically ill neonates, and magnetic resonance compatible incubator and ventilator can be used. (4) At present, 1.5 T or 3.0 T equipment can be used for neonatal brain MRI examination, and the special coil for the neonatal head should be used to improve signal-to-noise ratio; routine neonatal brain MRI sequences should at least include axial T1 weighted image (T1WI), axial T2 weighted imaging (T2WI), diffusion-weighted imaging, and sagittal T1WI or T2WI. (5) It is recommended to use a structured and graded reporting system, and reports by at least two reviewers and multi-center collaboration are recommended to increase the reliability of the report.
Brain/pathology* ; Consensus ; Humans ; Hypoxia-Ischemia, Brain/pathology* ; Infant ; Infant, Newborn ; Infant, Premature ; Magnetic Resonance Imaging/methods* ; Reproducibility of Results

OBJECTIVE: To observe the effect of aminophylline on physiological and pathological changes in acute exposure to high altitude in rats. METHODS: A total of 21 male Wistar rats were randomly divided into a plain group (altitude 55 m), a high altitude hypoxia group (altitude 4 300 m), and a high altitude hypoxia plus aminophylline group. After 5 days, blood from orbital venous was collected for analyzing biochemical parameters. Blood from abdominal aorta was collected for analyzing the parameters of blood gas. The tissues of brain, lung, and kidney were dissected for pathological observation. RESULTS: Compared with the plain group, the parameters of LDH, ALP, Urea and cCl? in the hypoxia group or the aminophylline treatment group were significantly increased (P<0.01), while the parameters of ALB, Cr, SatO₂, Hb, Hct, PaCO₂, PaO₂2, BB and BE were significantly reduced (P<0.01). Compared with the hypoxia group, the parameters of Cr, pH, Hct, cNa⁺, cCl⁻ in the aminophylline treatment group were significantly increased (P<0.01), while AST, ALT, ALB, PaCO₂ and cK⁺ were significantly decreased (P<0.01 or P<0.05). Pathological results showed the brain, lung and liver tissues were obviously damaged in the hypoxia group compared with that in the plain group. These damages were significantly attenuated by aminophylline. CONCLUSION Aminophylline can improve blood gas and biochemical parameters in acute exposure to high altitude in rats. It can protect rat brain, lung and liver from the damage caused by acute high altitude, which may be related its effects on relaxation of bronchial smooth muscle and inhibition of inflammation.
Altitude ; Aminophylline ; pharmacology ; Animals ; Brain ; pathology ; Hypoxia ; blood ; physiopathology ; Liver ; pathology ; Lung ; pathology ; Male ; Rats ; Rats, Wistar