Comparison between selective head cooling and whole-body cooling in neonatal therapeutic hypothermia / Comparação entre resfriamento seletivo da cabeça e resfriamento de corpo inteiro na hipotermia terapêutica neonatal

INTRODUCTION: Experimental evidence, as well as improved clinical studies of the reduction of brain injury and, improves the neurological outcome, in newborns with hypoxic-ischemic encephalopathy (HIE) occurring in therapeutic hypothermia (TH). OBJECTIVE: To verify the potential of hypothermic hypoxic-ischemic encephalopathy (HIE) therapy in neonatal asphyxia, based on literature data, comparing the benefits between selective head cooling (SHC) and whole-body cooling (WBC), see that the use of TH as a standard treatment in newborns with moderate or severe HIE has been adopted. METHODS: A search was performed in the PubMed and SciELO databases of human studies, using the keywords "Therapeutic Hypothermia", "Induced Hypothermia", and "Hypoxic-Ischemic Encephalopathy", "Selective cooling of the head", "Total body cooling" and its variables. RESULTS: Eleven articles were selected to compose the review, after detailed reading. There is a consensus, that the reduction of the risk of death or disability at 18 months of life in neonates with moderate to severe HIE, occurs to TH through the techniques of WBC or SHC. It was found in the studies that there is no difference in terms of adverse effects between the two methods. As for radiological changes, such as hypoxic-ischemic injuries and the incidence of seizures after cooling, they are more frequent with SHC. CONCLUSION: Both WBC and SHC demonstrated neuroprotective properties, although WBC provides a broader area of brain protection. However, no significant differences were found between the methods in terms of adverse effects and beneficial short or long-term results.

INTRODUÇÃO: Evidências experimentais, assim como estudos clínicos, sugerem a redução da lesão cerebral e melhora do desfecho neurológico, em recém-nascidos com encefalopatia isquêmica hipóxica (EHI) submetidos à hipotermia terapêutica (HT). OBJETIVO: Verificar a potencialidade da terapia hipotérmica de encefalopatia hipóxico-isquêmica (EHI) na asfixia neonatal, com base em dados da literatura, comparando os benefícios entre o resfriamento seletivo da cabeça (RSC) e o resfriamento de corpo inteiro (RCI), visto que o uso de hipotermia terapêutica (HT) como tratamento padrão em recém-nascidos com EHI moderada ou grave tem sido amplamente adotada. MÉTODOS: Foi realizada uma busca nas bases de dados PubMed e SciELO de estudos em humanos, utilizando-se as palavras-chave "Therapeutic Hypothermia", "Induced Hypothermia", "Hypoxic-Ischemic Encephalopathy", "selective head cooling", "whole body cooling" e suas respectivas variáveis. RESULTADOS: Foram selecionados 11 artigos para compor a revisão, após leitura detalhada. É consenso, a redução do risco de morte ou incapacidade aos 18 meses de vida nos neonatos com EHI moderado a grave, submetidos à HT através das técnicas de RCI ou RSC. Constatou-se diante dos estudos que não há diferença em termos de efeitos adversos entre os dois métodos. Quanto às alterações radiológicas, as lesões hipóxico-isquêmicas e incidência de convulsões após o resfriamento são mais frequentes com o RSC. CONCLUSÃO: Tanto RCI quanto o RSC demonstraram propriedades neuroprotetoras, embora o RCI proporcione uma área de proteção cerebral mais ampla. No entanto, não foram constatadas diferenças significativas entre os métodos quanto a efeitos adversos e a resultados benéficos em curto e longo prazo.

Neuroprotection and potential mechanism of xenon on neonatal hypoxic-ischemic encephalopathy / 中华围产医学杂志

Neonatal hypoxic-ischemic encephalopathy often causes long-term adverse effect on neurological system or even death in near-term or full-term infants, but no effective treatment is available currently. Studies have shown that xenon can reduce brain injury caused by hypoxia-ischemia and is promising in clinical practice. The possible mechanisms include antagonism to glutamic acid receptors, anti-apoptosis, promotion of cell repair and xenon preconditioning. This article reviews the mechanism and research progress on neuroprotection effect of xenon in the treatment of neonatal hypoxic-ischemic encephalopathy.

Role of Nrf2/GPX4 signaling pathway-mediated ferroptosis in midazolam-induced reduction of HIBD in neonatal rats / 中华麻醉学杂志

Objective:To evaluate the role of nuclear factor-erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase-4 (GPX4) signaling pathway-mediated ferroptosis in midazolam-induced reduction of hypoxic-ischemic brain damage (HIBD) in neonatal rats.Methods:Ninety healthy 7-day-old neonatal rats, weighing 16-20 g, were divided into 6 groups ( n=15 each) using the random number table method: sham operation group (Sham group), HIBD group, low-dose midazolam (10 mg/kg) group (group L), medium-dose midazolam (20 mg/kg) group (group M), high-dose midazolam (40 mg/kg) group (group H), and Nrf2 inhibitor ML385 group (group I). The HIBD model was developed by ligating the left carotid artery and exposing to a hypoxic condition for 2 h in anesthetized animals. Starting from 2nd day after developing the model, the corresponding doses of midazolam were intraperitoneally injected in midazolam groups, the equal volume of normal saline was intraperitoneally injected in Sham and HIBD groups, midazolam 40 mg/kg and Nrf2 inhibitor ML385 30 mg/kg were intraperitoneally injected once a day for 8 consecutive days in group I. The rats were weighed and subjected to the Morris water maze test after the end of administration. Blood samples were taken from the abdominal aorta after the end of the Morris water maze test, and then the animals were sacrificed to remove the brain for determination of the concentrations of serum iron, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay), contents of iron and GSH in hippocampal tissues (by ultraviolet spectrophotometry and micro method), the number of Nrf2/neuronal nuclear antigen (NeuN) and GPX4/NeuN positive cells (by immunofluorescent staining), and expression of Nrf2, GPX4, and 4-hydroxynonaenoic acid (4-HNE) in hippocampal tissues and for microscopic examination of the pathological changes of hippocampal neurons in brain tissues (after HE staining and Nissl staining). Results:Compared with Sham group, the first time to arrival at platform was significantly prolonged, the number of crossing the origional platform was reduced, and the time of staying at the target quadrant was shortened, the iron content in the hippocampal tissues was increased, the content of GSH and the number of Nrf2/NeuN and GPX4/NeuN positive cells were decreased, the expression of Nrf2 and GPX4 was down-regulated, the expression of 4-HNE was up-regulated, the concentrations of serum iron, IL-6 and TNF-α were increased, and the injury to hippocampal neurons was marked in HIBD group ( P<0.05). Compared with HIBD group, the first time to arrival at platform was significantly shortened, the number of crossing the origional platform was increased, and the time of staying at the target quadrant was prolonged, the iron content in the hippocampus tissues was decreased, the content of GSH and the number of Nrf2/NeuN and GPX4/NeuN positive cells were increased, the expression of Nrf2 and GPX4 was up-regulated, the expression of 4-HNE was down-regulated, the concentrations of serum iron, IL-6 and TNF-α were decreased ( P<0.05), and the injury to hippocampal neurons was significantly reduced in H, M and L groups. Compared with group H, the first time to arrival at platform was significantly prolonged, the number of crossing the origional platform was reduced, and the time of staying at the target quadrant was shortened, the iron content in the hippocampus tissue was increased, the content of GSH and the number of Nrf2/NeuN and GPX4/NeuN positive cells were decreased, the expression of Nrf2 and GPX4 was down-regulated, the expression of 4-HNE was up-regulated, the concentrations of serum iron, IL-6 and TNF-α were increased ( P<0.05), and the injury to hippocampal neurons was aggravated in group I. Conclusions:The mechanism by which midazolam reduces HIBD may be related to activation of the Nrf2/GPX4 signaling pathway and inhibition of hippocampal neuronal ferroptosis in neonatal rats.

Effect of Edaravone and dexborneol on oxidative stress pathway in peripheral blood of elderly patients with acute ischemic stroke / 中华老年医学杂志

Objective:To investigate the effect of Edaravone and dexborneol(Eda.B)on oxidative stress pathway in peripheral blood of elderly patients with acute ischemic stroke.Methods:A total of 87 elderly patients with acute ischemic stroke in the Department of Neurology, Qinghai University Affiliated Hospital from July 2021 to January 2022 were selected as the study subjects.According to the random number table, they were divided into control group(44 cases)and edaravone dexborneol group(43 cases). Each group was divided into <12 h group, 12-24 h group and 24-48 h group according to the time of onset.Peripheral blood was collected in each group at admission and discharge, respectively.The serum levels of reactive oxygen species(ROS), Kelch-like epichlorohydrin-associated protein 1(Keap1), nuclear factor-E2-associated factor 2(Nrf2), heme oxygenase-1(HO-1), NAD(P)H quinone oxidoreductase 1(NQO1), tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6), as well as superoxide dismutase(SOD)activity and malondialdehyde(MDA)content were detected.Results:Elderly patients with acute ischemic stroke receving Eda.B treatment after admission could reduce the serum concentration of ROS, TNF-α and IL-6, as well as MDA content, and increase the concentration of Keap1, Nrf2, HO-1 and NQO1 and SOD activity.Except for ROS concentration in <12 h group and SOD activity in <12 h and 12 h-24 h groups, the differences between the other groups were statistically significant( P<0.05 for all). Compared with the control group, the serum concentration of TNF-α and IL-6 of patients in the Eda.B group at discharge decreased, while the concentration of Nrf2(24-48 h group)and HO-1(24-48 h group), and SOD activity increased, the differences were statistically significant( P<0.05 for all). In the control group at discharge, the concentrations of ROS(24-48 h group), TNF-α(<12 h group, 24-48 h group)and IL-6, as well as MDA content decreased, while the concentrations of Keap1, Nrf2(<12 h group, 12-24 h group)and HO-1(<12 h group, 12-24 h group)increased, the differences were also statistically significant( P<0.05 for all). Compared with admission, the concentration of Keap1(24-48 h group)and HO-1(24-48 h group), the activity of SOD(<12 h group, 12-24 h group)increased and the content of MDA(12-24 h group)in the Eda.B group decreased at discharge( P<0.05 for all). Conclusions:Eda.B can reduce oxidative stress and inflammatory response in peripheral blood of elderly patients with acute ischemic stroke by acting on the Keap1/Nrf2 pathway.

Hipotermia terapéutica para tratamiento de encefalopatía hipóxico-isquémica del recién nacido asfixiado: Características clínicas, radiológicas y electrográficas de los neonatos atendidos en el Instituto Nacional Materno Perinatal

La encefalopatía hipóxico-isquémica (EHI) es el síndrome neurológico causado por la asfixia perinatal. La hipotermia terapéutica (HT) ha demostrado reducir la mortalidad y morbilidad asociadas a EHI. Se realizó un estudio descriptivo retrospectivo con 30 recién nacidos con EHI moderada y severa que recibieron HT en la Unidad de Cuidados Intensivos del Instituto Materno Perinatal desde setiembre de 2017 a noviembre de 2020. Nueve de los casos fueron severos (30 %). El tiempo promedio de ingreso a HT fue 3.4 horas de vida. No se registraron efectos adversos importantes atribuibles a HT. Todos los pacientes severos tuvieron crisis epilépticas, ecografías cerebrales de ingreso y resonancias con anormalidades. La mortalidad fue de 20.0 %, aunque fue significativamente menor en el grupo con EHI moderada. Se identificaron las características de presentación clínica, electrográfica y radiológica de los neonatos con EHI que recibieron hipotermia terapéutica, la cual se muestra como un procedimiento seguro y efectivo.

Hypoxic-ischemic encephalopathy (HIE) is the neurological syndrome caused by perinatal asphyxia. Therapeutic hypothermia (TH) has been shown to reduce HIE-associated morbidity and mortality. A descriptive and retrospective study with 30 newborns with moderate and severe HIE who underwent TH in the Intensive Care Unit (ICU) of Instituto Materno Perinatal, from September 2017 until November 2020. Nine patients were severely affected (30%). The average tome for being admitted in the ICU was at 3.4 hours of life. No important adverse effects attributable to TH were observed. All severely affected patients experienced epileptic crises, and abnormal cerebral ultrasonography and magnetic resonance imaging studies on admission. Mortality was 20.0%, but it was significantly lower in the group with moderate HIE. Clinical, electrographic, and radiological characteristics of neonates with HIE who underwent therapeutic hypothermia were identified. This procedure has been shown to be safe and effective.

Influential factors of neonatal hypoxic ischemic encephalopathy and the therapeutic effects of mild hypothermia at different time windows / 中国基层医药

Objective:To investigate the influential factors of neonatal hypoxic ischemic encephalopathy (HIE), and compare the therapeutic effects of mild hypothermia at different time windows and between different degrees of disease severity.Methods:Eighty-two neonates with HIE who were admitted to Jiaxing Maternity and Child Health Care Hospital from January 2016 to October 2021 were included in the patient group, and 123 concurrent healthy neonates were included in the control group. The influential factors of neonatal HIE were analyzed. Sixty-five neonates who received HIE were divided into four groups according to the time length between symptom onset and hospital admission (< 6 hours and 6-12 hours) and disease severity: group I (admission time < 6 hours, mild, n = 20), group II (admission time < 6 hours, moderate to severe, n = 15), group III (admission time 6-12 hours, mild, n = 17), and group IV (admission time 6-12 hours, moderate to severe, n = 13). Amplitude-integrated electroencephalography (aGGE) score was used as the evaluation criteria. The therapeutic effects of mild hypothermia were compared between different time windows and between different degrees of HIE. Results:Multivariable logistic regression analysis results revealed that the influential factors of neonatal HIE included gestational hypertension, gestational diabetes, pregnancy examination, delivery methods, amniotic fluid contamination, abnormal fetal membranes (placenta or umbilical cord), fetal distress, and neonatal asphyxia ( P < 0.05). All 65 neonates with HIE underwent mild hypothermia treatment for 72 hours. Before treatment, aGGE score in groups I, II, III and IV was 6.02 ± 1.74 points, 2.43 ± 1.82 points, 5.23 ± 1.95 points, and 2.72 ± 1.76 points, respectively. After treatment, it was 8.13 ± 2.03 points, 6.47 ± 1.87 points, 7.86 ± 1.92 points, and 3.52 ± 1.95 points, respectively. There was significant difference in aGGE score between before and after treatment in groups I, II and III ( t = 2.87, 3.55, 3.15, all P < 0.05). aGGE score in group IV did not differ significantly between before and after treatment ( P > 0.05). Before treatment, aGGE score in children with moderate to severe HIE was lower than that in children with mild HIE. After treatment, there was no significant difference in aGGE score between groups II and III ( P > 0.05). Conclusion:Pregnant women with gestational hypertension and gestational diabetes should be given intensive monitoring and learn HIE related knowledge to increase the frequency of prenatal examinations. If amniotic fluid contamination, abnormal fetal membranes (placenta or umbilical cord), fetal distress, or neonatal asphyxia occurs, timely monitoring and corresponding interventions should be given to the fetus. Mild hypothermia therapy has a certain therapeutic effect on different degrees of HIE. For moderate to severe neonates, treatment should be started within 6 hours to ensure the therapeutic effects of mild hypothermia.

Effects of abdominal massage on the exercise and balance of rats with neonatal hypoxic-ischemic brain injury via 5-HTR1A/cAMP/PKA signaling pathway / 国际中医中药杂志

Objective:To explore the effect of abdominal massage on the behavior of rats with neonatal hypoxia-ischemia and its mechanism.Methods:7-day-old SD rats were made as the HIBD model by the classical method of RICE and then the HIBD model rats were divided into the abdominal massage group and model group according to the random number table method, with 12 rats in each group, and 12 rats were selected as the normal group. The abdominal massage group was given abdominal massage 24 hours after the modeling, and the intervention continued for 28 days. Rats in each group underwent a balance beam test on the 7th, 14th, 21st, and 28th day of the intervention. After the intervention, HE staining was applied to observe the morphological structure of the hippocampal CA1 region of the rats; Quantitative Real-time PCR method was used to measure the serotonin receptor (5-HTR1A) in the hippocampus. The expression of cAMP, PKA and CREB in the hippocampus were measured by immunohistochemistry, and the expression of SYP protein was measured by Western blotting.Results:After the intervention, the cells in the hippocampal CA1 area of the model group were diffusely distributed, the number of neurons reduced, and the condition of inflammatory edema appeared; the cells in hippocampal CA1 area of the abdominal massage group were arranged clearly, and the condition of inflammatory edema has significantly improved; on the 21st and 28th day of the intervention, the balance beam test scores in the abdominal massage group significantly decreased ( P<0.05), and the relative expression of 5-HTR1A mRNA (1.18±0.08 vs. 0.77±0.04) in the abdominal massage group significantly increased ( P<0.05). The expression of cAMP (0.32±0.02 vs. 0.31±0.01), PKA (0.32±0.02 vs. 0.29±0.01),CREB (0.31±0.02 vs. 0.28±0.01) and SYP in the abdominal massage group significantly increased ( P<0.05). Conclusion:Abdominal massage could improve the behavior of neonatal hypoxic-ischemic rats, which may play a role on nerve repair by regulating 5-HTR1A/cAMP/PKA signaling pathway.

Research progress in pathogenesis, diagnosis and treatment of traumatic pseudo subarachnoid hemorrhage / 中华创伤杂志

Pseudo subarachnoid hemorrhage (PSAH) is often secondary to resuscitation or severe traumatic brain injury (TBI) and has a high rate of mortality and disability. It is characterized by symmetrical subarachnoid hyper-density opacities on CT scans and is mainly venous reflux disorder caused by diffuse cerebral swelling for various causes. At present, PSAH is primarily examined by CT with reduction of cranial pressure as the treatment method. However, the CT signs of PASH are similar to subarachnoid hemorrhage caused by ruptured aneurysm, so the positive CT screening rate for PSAH is low. Effect of simple reduction of intracranial pressure on prognosis improvement of PSAH patients is also limited. Clinical understanding of PSAH is still insufficient, resulting in missed or false diagnosis and untimely treatment. The authors review the research progress in pathophysiology, diagnosis and treatment methods of PSAH so as to help clinicians better understand PSAH, make early diagnosis and timely treatment and improve patients′ prognosis.

An adjustable anti-snoring device improves brain oxygen supply and chronic cerebral circulation insufficiency in patients with obstructive sleep apnea syndrome / 中国基层医药

Objective:To investigate the efficacy of an adjustable anti-snoring device in improving brain oxygen supply and chronic cerebral circulation insufficiency in patients with obstructive sleep apnea syndrome (OSAS).Methods:Thirty-four patients with OSAS who received treatment in Huidong People's Hospital from January to September 2018 were included in the OSAS group. An additional 34 sex- and age-matched healthy volunteers who concurrently received physical examination were included in the control group. Apnea-hypopnea index score for each patient was determined by polysomnography. Cerebral blood flow velocity was measured by transcranial Doppler ultrasonography. Forearm blood flow was measured by venous occlusion plethysmography. Heart rate was obtained by electrocardiography. Arterial oxygen saturation (SaO 2) was obtained using pulse oximetry. Blood pressure was obtained by an automatic sphygmomanometer. Peripheral and cerebral hemodynamics of patients with OSAS were measured. Nighttime sleep quality of patients was assessed using polysomnography. Lateral projection of the skull was photographed using an X-ray machine for correcting measurement results. Results:There were no significant differences in sex and age between OSAS and control groups (both P > 0.05). Body mass index, Apnea-hypopnea index score and the percentage of time spent at SaO 2 below 90% in the OSAS group were significantly higher than those in the control group (all P < 0.05). The lowest SaO 2 value in the OSAS group was significantly lower than that in the control group ( P < 0.05). Heart rate and forearm blood flow in the OSAS group were (76.27 ± 9.34) beats/min and (7.24 ± 3.13) mL·100 mL -1·min -1, respectively, which were significantly higher than those in the control group [(65.42 ± 6.38) beats/min, (4.11 ± 1.25) mL·100 mL -1·min -1]. After treatment with an adjustable anti-snoring device, heart rate and forearm blood flow in the OSAS group were (66.17 ± 4.53) beats/min and (4.54 ± 3.26) mL·100 mL -1·min -1, respectively, which were significantly lower than those in the control group ( F = 2.66, 0.85, both P < 0.05). Peripheral oxygen saturation, tissue oxygen saturation, and total hemoglobin in the OSAS group were significantly lower than those in the control group. These indexes in the anti-snoring device treatment group were significantly higher than those in the OSAS group ( F = 12.33, 13.57, 14.22, all P < 0.05). The number of snorings and number of wake-ups from sleep in the anti-snoring device treatment group were significantly lower compared with those in the OSAS group ( χ2 = 13.14, 12.36, both P < 0.05).Palatopharyngeal diameter, glossopharyngeal diameter and laryngopharyngeal diameter in the anti-snoring device treatment group were significantly higher than those in the OSAS group, and they were almost close to the levels of healthy people ( t = 11.46, 15.13, 12.58, all P < 0.05). Conclusion:Adjustable anti-snoring device can improve brain oxygen supply and chronic cerebral circulation insufficiency in patients with OSAS, in particular with mild and moderate OSAS.

The regulatory effects of transforming growth factor beta-activated kinase 1 on microglia pyroptosis in hypoxic-ischemic brain damage / 中国新生儿科杂志

Objective:To study the regulatory effects of transforming growth factor beta-activated kinase 1 (TAK1) on microglia pyroptosis in hypoxic-ischemic brain damage (HIBD).Methods:Primary microglia cells were isolated from fetal mice and randomly assigned into 4 groups: the control group, 5z-7-oxozeaneol (5z-7) group, oxygen-glucose deprivation (OGD) group and OGD+5z-7 group. OGD models of microglia cells were established for the OGD groups and 5z-7 groups received a small molecule TAK1 inhibitor 5z-7. Expression of phosphorylated TAK1(P-TAK1), pyroptosis related proteins including NOD-like receptor pyrin domain containing 3 (NLRP-3), apoptosis-associated speck-like protein containing a CARD (ASC) oligomers, N terminal of Gasdermin D (GSDMD-N) and interleukin 1β (IL-1β) were examined using Western blot at 0 h, 6 h and 24 h after intervention. Lactate dehydrogenase (LDH) test and transmission electron microscope were used for pyroptosis evaluation.Results:(1) Compared with the control group, expressions of all proteins including P-TAK1, NLRP-3, ASC oligomers, GSDMD-N, IL-1β and LDH level showed no significant differences in the OGD group at 0 h ( P>0.05). P-TAK1 levels in OGD group at 6 h and 24 h were lower than the control group and the levels of NLRP-3, ASC oligomers, GSDMD-N, IL-1β and LDH were significantly higher ( P<0.05). Microglia pyroptosis (characterized by disruption of cell membrane, extravasation of cytoplasm and chromatin margin aggregation) was observed under electron microscope. (2) 5z-7 group and OGD+5z-7 group had lower P-TAK1 levels and higher NLRP-3, ASC oligomers, GSDMD-N, IL-1β and LDH levels than the control group and OGD group at 6 h and 24 h. Conclusions:The down-regulation of TAK1 phosphorylation level may promote microglia pyroptosis in HIBD. This regulatory effects is related to the up-regulation of NLRP-3 expression and the oligomerization of ASC.

Effect of overexpressed zinc finger protein 580 on apoptosis of oxygen-glucose deprivation SH-SY5Y cells and its possible mechanism / 中华围产医学杂志

Objective:To investigate the expression of zinc finger protein 580 (ZNF580) in oxygen-glucose deprivation (OGD) model of SH-SY5Y cell line and its overexpression on the apoptosis of hypoxic-ischemic neurons and the possible mechanism.Methods:The study was divided into two parts: (1) Human neuroblastoma SH-SY5Y cell line was cultured and divided into the model group and control group. The model group was incubated at 37 ℃ for 6 h in a three-gas incubator of 95% N 2, 5% CO 2, and 0.1% O 2 to establish OGD model, and proteins were extracted at 6, 12, and 24 h after OGD. The expression of ZNF580 was quantified by Western blot. (2) Effects of ZNF580 overexpressed with lentivirus transfection on the apoptosis and cleaved caspase-3 expression: Cells were collected from the control group and model group 24 h after OGD. Overexpressed ZNF580 cells were constructed by lentivirus transfection as the overexpression group and then treated with OGD. Flow cytometry was used to detect the apoptosis rate in the three groups and Western blot was used to detect the expression of cleaved caspase-3. Two independent sample t-test, one-way variance analysis, and LSD- t for pairwise comparison were used for statistical analysis. Results:(1) ZNF580 expression was significantly increased at 6, 12, and 24 h after OGD compared with the control group (1.36±0.05, 2.12±0.07, 1.69±0.05 vs 1.00, LSD- t=9.20, 28.26, and 19.21, all P<0.001). (2) Apoptosis rates of the control, model, and overexpression groups were (1.07±0.56)%, (21.51±1.65)%, and (3.42±0.93)%, respectively, and relative expression levels of cleaved caspase-3 were 1.00, 2.47±0.59, and 1.70±0.25, respectively. Compared with the control group, apoptosis rate and cleaved caspase-3 relative expression level were significantly increased in the model group (LSD- t=21.98 and 8.17, both P=0.001), while the two figures were significantly decreased in the overexpression group when compared with the model group (LSD- t=19.45, P=0.001; LSD- t=4.28, P=0.005). Conclusion:Hypoxia and ischemia could lead to the overexpression of ZNF580, which may reduce the apoptosis of hypoxic-ischemic neurons by inhibiting the expression of cleaved caspase-3 and affecting its enzymatic activation.

Research progress in high mobility group box-1 in hypoxic-ischemic brain damage / 中华围产医学杂志

Inflammation plays an important part in neonatal hypoxic-ischemic brain damage (HIBD). High mobility group box-1 protein (HMGB1), a neuroinflammatory trigger, has a dual effect on HIBD: in the acute stage, it amplifies the ischemic tissue injury; in the later stage, it is involved in the neurovascular repair and reconstruction. The significance of HMGB1 in the pathogenesis of HIBD is still not fully understood. This review summarizes the role of HMGB1 in HIBD, including its effects on neurons, glial cells and blood-brain barrier, and the underlying mechanisms as well as the progress in research on HMGB1 in immature brain, hoping to provide new ideas for neuroprotection in HIBD.

Prolongación del intervalo QT durante hipotermia terapéutica en un recién nacido con encefalopatía hipóxico isquémica: a propósito de un caso / Prolongation of the QT interval during therapeutic hypothermia in a newborn with hypoxic-ischemic encephalopathy: A case report / Prolongamento do intervalo QT durante hipotermia terapêutica em recém-nascido com encefalopatia hipóxico-isquêmica: relato de caso

Resumen: El síndrome de QT largo adquirido puede ser secundario a la hipotermia, tanto accidental como terapéutica. Es poco el conocimiento sobre el efecto de ésta en la actividad eléctrica cardíaca, sobre todo en recién nacidos, y sus potenciales complicaciones. Se presenta el caso clínico de un recién nacido con diagnóstico de encefalopatía hipóxico isquémica que presenta una prolongación del intervalo QT durante el tratamiento con hipotermia. Se discute la evolución del paciente, que es consistente con lo referido en la literatura sobre el tema: buena evolución, ausencia de arritmias graves o alteraciones hemodinámicas, y normalización del electrocardiograma luego de finalizado el tratamiento.

Summary: Acquired long QT syndrome may be secondary to hypothermia, both accidental and therapeutic. There is not enough knowledge about the effect of hypothermia in cardiac activity and its potential complications, especially in newborns. We present the clinical case of a newborn with a diagnosis of hypoxic ischemic encephalopathy who has a prolonged QT interval during treatment with hypothermia. The evolution of the patient is discussed, which is consistent with what is referred to in the literature on the subject: Good evolution, absence of serious arrhythmias or hemodynamic alterations, and normalization of the ECG after the end of treatment.

Resumo: A síndrome do QT longo adquirida pode ser secundária à hipotermia, tanto acidental quanto terapêutica. Pouco se sabe sobre seu efeito na atividade elétrica cardíaca, principalmente em recém-nascidos, e suas possíveis complicações. Apresentamos o relato de caso clínico de um recém-nascido com diagnóstico de encefalopatia hipóxica isquêmica que apresenta prolongamento do intervalo QT durante o tratamento com hipotermia. Discutimos a evolução do paciente, a que é consistente com a literatura sobre o assunto: boa evolução, ausência de arritmias graves ou alterações hemodinâmicas e normalização do ECG após o término do tratamento.

Inserción "velamentosa", encefalopatía hipóxico-isquémica y rehabilitación neurológica: reporte de caso / Velamentous cord insertion, ischemic-hypoxic encephalopathy, and neurological rehabilitation: A case report

Resumen. La encefalopatía hipóxico-isquémica es una causa frecuente e importante de daño neurológico en recién nacidos a término y prematuros. Un evento centinela de esta condición es la vasa previa, específicamente cuando existe anormalidad de la placenta como la inserción "velamentosa" del cordón umbilical. Algunos reportes evidencian la asociación entre estas dos condiciones, pero son escasos los que dan cuenta del proceso de recuperación y del pronóstico neurológico de los niños afectados por ellas. Se presenta el caso de un paciente, con antecedentes de inserción "velamentosa" del cordón umbilical y encefalopatía hipóxico-isquémica, que recibió hipotermia terapéutica (cool cap). Se describe su proceso de rehabilitación neurológica y se calculó el porcentaje de probabilidad de presentar esta condición frente a la población sin estos factores. El niño tenía cinco años y el puntaje en su prueba de Apgar fue de 0 al minuto y de 2 a los 15 minutos. Desarrolló encefalopatía hipóxico-isquémica grave secundaria a una inserción "velamentosa" del cordón umbilical sin diagnóstico prenatal, con gran compromiso neurológico y multisistémico inicial. El proceso de recuperación incluyó el manejo inicial multidisciplinario en la unidad de cuidados intensivos neonatales y el inicio temprano de habilitación neurológica. Hoy el niño está escolarizado y en terapia integral, no presenta deficiencias motoras ni sensoriales en el examen físico, aunque la prueba neuropsicológica sugiere un riesgo de trastorno por déficit de atención e hiperactividad. Habitualmente, los niños con encefalopatía hipóxico-isquémica grave presentan discapacidad por deficiencias motoras, cognitivas o conductuales. El haber recibido hipotermia terapéutica y un manejo estructurado de rehabilitación redujo en gran medida las deficiencias esperadas y ha promovido un satisfactorio desarrollo físico y neurológico.

Abstract. Hypoxic-ischemic encephalopathy is a frequent and important cause of neurological problems in term and preterm newborns. A sentinel event of this entity is the vasa previa, specifically when there is an abnormality of the placenta such as a velamentous cord insertion. Some reports have shown the association between these two entities, but those regarding the recovery process and the neurological prognosis of children with both conditions are scarce. We present the case of a patient with a history of velamentous cord insertion and hypoxic-ischemic encephalopathy who received therapeutic hypothermia (cool cap). We describe his neurological rehabilitation process and we calculated the percentage of probability of presenting this condition compared to the population without these factors. The patient was a five-year-old boy with an Apgar index at birth equal to zero at one minute and equal to two at fifteen minutes who developed severe hypoxic-ischemic encephalopathy secondary to a velamentous cord insertion without prenatal diagnosis and a marked initial neurological and multisystemic compromise. The recovery process included early multidisciplinary management in the neonatal intensive care unit and a focus on early neurological habilitation. The patient is currently in school and he undergoes comprehensive therapies; on physical examination, he presents no motor or sensory deficiencies. His neuropsychological test suggests the risk of attention deficit hyperactivity disorder. Children with severe hypoxic-ischemic encephalopathy usually have disabilities due to motor, cognitive, and/or behavioral deficiencies. Having received therapeutic hypothermia and a structured rehabilitation process greatly reduced the expected deficiencies according to prognosis and have promoted satisfactory physical and neurological development.

The efficacy of systemic hypothermia therapy initiated at different times on neonatal hypoxic-ischemic encephalopathy / 中国新生儿科杂志

Objective:To study the clinical efficacy, safety and prognosis of systemic hypothermia therapy on neonatal hypoxic-ischemic encephalopathy (HIE)initiated at different times after birth.Method:From January 2013 to August 2018, term neonates (within 12 hours after birth) diagnosed with neonatal moderate to severe HIE and received systemic treatment in the neonatal intensive care unit of our hospital were retrospectively included. According to the starting time of hypothermia therapy, the neonates were assigned into three groups: within 6 h after birth (TH1 group), 6~12 h (TH2 group) and conventional treatment group (control group). Their clinical data during perinatal period, hospitalization period and follow-up at 6-month were reviewed. Their clinical and neurodevelopmental outcomes were compared using SPSS 25.0 statistical software.Result:A total of 147 neonates with moderate to severe HIE were enrolled. 111 received 72-hour hypothermia therapy, including 79 in the TH1 group, 32 in the TH2 group and 36 in the control group. The neurobehavioral test scores at 10-day of life in the TH1 group were significantly higher than the control group ( P<0.05). No significant differences existed among the TH2 group, the TH1 group and the control group ( P>0.05). The brain magnetic resonance imaging (MRI) showed injuries in the TH1 group and the TH2 group were significantly milder than the control group ( P<0.05). No significant differences of brain injuries existed between TH1 group and TH2 group ( P>0.05). 100 patients completed Bailey Infant Intelligence Development Scale at 6-month follow-up. 21 had abnormal scores. No statistically significant differences existed in the psychomotor development index (PDI) scores among the three groups ( P>0.05). TH1 and TH2 groups had significantly fewer cases with mental development index (MDI) <70 points than the control group ( P<0.05). No statistically significant differences existed of MDI scores between the TH1 group and the TH2 group ( P>0.05). No statistically significant differences existed of PDI scores among the 3 groups ( P>0.05). At 6-month, the mortality rate of the control group (32.1%, 9/28) was significantly higher than the TH1 group (6.6%, 4/61) ( P<0.05). No significant differences existed of mortality rate at 6-month among the TH2 group, the TH1 group and the control group ( P>0.05). Conclusion:Systemic hypothermia therapy for neonatal HIE is safe. Starting systemic hypothermia therapy at 6~12-hour after birth may also be effective in reducing mortality rate and improving neurodevelopmental outcome.

Differential expressions of miRNAs in peripheral blood of neonatal rats in the hypoxia-ischemia injury with self-resuscitation model / 中华实用儿科临床杂志

Objective:To assess the changes in profiles of microRNAs (miRNAs) in peripheral blood of neonatal Sprague-Dawley (SD) rats with hypoxia-ischemia(HI) injury with self-resuscitation.Methods:Neonatal rats of 3 pregnant rats were divided into 3 groups according to their nests, in which group A was the blank control group, group B was the HI group, and group C was the alternative group.The expression profiles of miRNAs in periphe-ral blood of neonatal rats in group A and B by high-throughput sequencing was compared.Bioinformatics analysis was applied to investigate these differentially expressed miRNAs.Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to screen out enriched signaling pathways and functions.Target genes of miRNAs and those correlated with hypoxia-ischemia brain damage were predicted using miRBaseData (miRBD) software.HE staining was performed to observe the pathological changes of rat brain tissues.Results:A total of 1 049 mature reliable miRNAs in peripheral blood of neonatal rats were identified, including 525 miRNAs in group A, and 524 in group B. There were 27 differentially expressed miRNAs between group A and B, and their types were highly correlated.A total of 38 dysregulated miRNAs were screened out in group B, involving 21 upregulated miRNAs and 17 downregulated ones.GO and KEGG analyses showed that the identified differentially expressed miRNAs were mainly enriched in the glutamatergic synapse pathway, myelin lipid metabolism, neural activity ligand-receptor interaction and the vascular epithelial growth factor (VEGF) signaling pathway, all of them were significantly correlated with HIBD and over-activated.Cortex and subcallosal white matter lesions, enlarged ventricles, disordered arrangement of gray matter neurons, and obvious apoptosis in rat brain tissues of group A and B were not observed in HE staining.Conclusions:Differential expression of miRNAs in peripheral blood of HI self-resuscitated rats suggests that miRNAs has a positive response to hypoxia and ischemia.Differentially expressed miRNAs, including miR-200, miR-471, miR-429, miR-216 and miR-871 families, in peripheral blood of neonatal rat with HI showed their active response after HIBD.They are related to the molecular mechanisms of the nervous system damage, and are expected to become novel diagnostic markers for HIBD or HI.Differentially expressed miRNAs are conductive to the development of therapeutic targets of HI.

Hipotermia terapêutica na encefalopatia hipóxico-isquêmica neonatal: revisão integrativa / Therapeutic hypothermia in neonatal hypoxic-ischemic encephalopathy: integrative review / Hipotermia terapéutica em la encefalopatía hipóxico-isquémica neonatal: revisión integrativa

Objetivo: identificar evidências acerca do uso seguro da hipotermia terapêutica em recém-nascidos. Método: revisão integrativa realizada entre junho e julho de 2018, em fontes eletrônicas da Biblioteca Virtual de Saúde e PubMed, por meio da pergunta:"Que evidências podem subsidiar o cuidado de enfermagem voltado para a redução de sequelas em recém-nascidos submetidos à hipotermia terapêutica?".Foram eleitos nove artigos para análise, sendo oito internacionais e um nacional. Resultados:o resfriamento deve acontecer por 72 horas, com hipotermia leve. As indicações para inclusão no protocolo foram: primeiras seis horas de vida, idade gestacional maior que 35 semanas e acidose na primeira hora de vida.São cuidados essenciais: monitoração hemodinâmica, observação da pele, controle térmico retal, vigilância do Eletroencefalograma de Amplitude Integrada. Conclusão: a terapêutica apresenta benefícios, porém sua aplicação depende de protocolo institucional e treinamento das equipes com foco nas potenciais complicações.

Objective: to identify the evidence on safe use of therapeutic hypothermia in newborns. Method: integrative review of the literature, conducted between June and July of 2018, in electronic sources from the Virtual Health Library and PubMed, through the question: "What evidence can support nursing care aimed at reducing sequelae in newborns undergoing therapeutic hypothermia?". Analysis was conducted for nine selected article, being eight from international literature and one from Brazilian national literature. Results: cooling should occur for 72 hours with mild hypothermia. Indications for inclusion in the protocol were: first six hours of life, gestational age greater than 35 weeks and acidosis in the first hour of life. Essential care includes hemodynamic monitoring, skin observation, rectal thermal control, Integrated Amplitude Electroencephalogram surveillance. Conclusion: the therapy has benefits, but its application depends on institutional protocol and team training focusing on potential complications.

Objetivo: identificar la evidencia sobre el uso seguro de la hipotermia terapéutica en recién nacidos. Método: revisión integradora de la literatura, realizada entre junio y julio de 2018, en fuentes electrónicas de la Biblioteca Virtual de Salud y PubMed, a través de la pregunta: "¿Qué evidencia puede apoyar la atención de enfermería dirigida a reducir las secuelas en los recién nacidos que sufren hipotermia terapéutica?". Se realizaron análisis para nueve artículos seleccionados, ocho de literatura internacional y uno de literatura nacional brasileña. Resultados: el enfriamiento debe ocurrir durante 72 horas con hipotermia leve. Las indicaciones para la inclusión en el protocolo fueron: primeras seis horas de vida, edad gestacional mayor de 35 semanas y acidosis en la primera hora de vida. El cuidado esencial incluye monitoreo hemodinámico, observación de la piel, control térmico rectal, vigilancia integrada de electroencefalograma de amplitud. Conclusión: la terapia tiene beneficios, pero su aplicación depende del protocolo institucional y del entrenamiento del equipo, enfocándose en posibles complicaciones.

Protective effects of endothelial progenitor cells-derived microvesicles on hypoxic-ischemic brain damage in newborn rats / 中国新生儿科杂志

Objective To study the protective effects and preliminary mechanisms of endothelial progenitor cells-derived microvesicles (EPC-MVs) on hypoxic-ischemic brain damage (HIBD) in newborn rats by using the HIBD model.Method Rat endothelial progenitor cells (EPCs) were cultured and microvesicles were extracted from EPCs culture medium by ultracentrifugation.A total of 60 neonatal SD rats were randomly assigned into control group,HIBD group,saline group and EPC-MVs group.The HIBD model was prepared in HIBD group,saline group and EPC-MVs group.After the preparation of the HIBD model,rats in saline group and EPC-MVs group received intraventricular injection with saline and EPC-MVs,respectively.After 72 hours,the rats were sacrificed for brain tissue,cerebral infarction was detected by TTC staining,vascular endothelial growth factor (VEGF) mRNA was tested by real-time PCR,protein western blot was used to detect changes in VEGF protein expression.Result Cells extracted and cultured from the spleen of 12-week-old SD rats were confirmed as EPCs by morphology and flow cytometry.EPC-MVs isolated by high-speed centrifugation from EPCs culture supernatant met the morphological characteristics of microvesicles by transmission electron microscopy.The infarcted brain tissue was not detected in the control group.The cerebral infarction volume ratios of HIBD group,saline group and EPC-MVs group were (80.3 ± 6.3) ％,(77.9 ± 8.9) ％,(35.2 ± 7.7) ％,respectively.The infarct volume of EPC-MVs group was significantly lower than that of HIBD group and saline group (P ＜ 0.001).The expression of VEGF mRNA and protein in HIBD group,saline group and EPC-MVs group were higher than those in control group (P ＜0.001).Among them,EPC-MVs group had the most significant increase,compared with the other three experimental groups,and the difference was statistically significant (P ＜ 0.001).There was no significant difference between saline group and HIBD group in the expression of VEGF mRNA and protein (P ＞ 0.05).Conclusion Intraventricular injection of EPC-MVs can attenuate HIBD in neonatal rats,and the mechanism may be related to up-regulation of VEGF expression.

MRI features of adult hypoxic-ischemic encephalopathy / 中国医学影像技术

Objective: To investigate the MRI features of adult hypoxic-ischemic encephalopathy. Methods: Data of 18 patients who underwent MR scanning after ischemia and hypoxia due to various reasons were collected and analyzed. Results: Among 18 patients, 17 were found with abnormal MRI signals, involving cerebral cortex, subcortical white matter, deep white matter, lateral ventricle white matter, corpus callosum, basal ganglia, hippocampus, thalamus, pons and cerebellum. Diffuse brain atrophy was shown in 9 patients, while plain T1WI showed hyper-intensity along the cerebral cortex or basal ganglia in 5 cases. Restricted diffusion was shown on DWI in 9 cases. Enhanced MR scanning was performed in 5 patients and showed mild gyral enhancement in cerebral cortex in 1 patient. MRI showed no obvious lesion in 1 case. Conclusion: MRI can display abnormal signals of hypoxic ischemic encephalopathy involving many brain regions. MRI features can not only reflect the severity of hypoxic-ischemic encephalopathy, but also predict treatment effect and evaluate the prognosis of patients.

Impact of hypoxic-ischemic injury on brain development in neonatal rats of different sexes / 中华儿科杂志

Objective@#To investigate the impact of hypoxic-ischemic brain injury (HIBI) on brain development in neonatal rats of different sexes.@*Methods@#From January 1 to December 31, 2018, 60 7-day-old SD rats were randomly divided into HIBI-F group (20 rats), HIBI-M group (20 rats), and control group (20 rats, 10 females and 10 males). The animal model of HIBI was established with Rice-Vannucci method, with the rats′ left common carotid artery double-ligated and severed. The rats were then placed in an incubator and exposed to a hypoxic gas mixture (8% O2, 92% N2) for 90 minutes. No intervention was given to the control group. Two weeks after HIBI, the motor development was evaluated by footprint analysis, the residual brain volume was measured by brain magnetic resonance imaging (MRI), and the damage of synaptic ultra structure was analyzed by transmission electron microscope. One-way ANOVA or χ2 test was used for inter-group statistical analysis, and paired sample t test was used to compare the bilateral step length and toe distance of rats in the same group.@*Results@#The mortality rate of HIBI-F was significantly higher than that of HIBI-M (20%(4/20) vs. 10%(2/20), χ2=40.000, P=0.001). The right step length and toe distance in HIBI-M group and HIBI-F group were significantly shorter than those in control group ((7.5±0.3) cm and (7.9±0.5) cm vs. (8.2±0.5) cm, F=9.605, P<0.01, (0.9±0.1) cm and (1.0±0.0) cm vs. (1.1±0.1) cm, F=71.437, P<0.01). Besides, according to above data, the right step length and toe distance in HIBI-M group were significantly shorter than those in the HIBI-F group (both P<0.01). Furthermore, the right step length was significantly shorter than the left step length ((8.3±0.4) and (8.3±0.5) cm, t=5.289 and 10.580, P=0.001 and 0.010, respectively) and toe distance ((1.1±0.1) and (1.1±0.1) cm, t=7.953 and 6.435, respectively, both P<0.01) in both HIBI-M group and HIBI-F group. Similarly, the synaptic gap of the left precentral gyrus neurons was longer in HIBI-M group and HIBI-F group than that in control group ((23.4±1.3) and (19.7±1.6) nm vs. (18.9±0.6) nm, F=71.719, P<0.01), and also longer in HIBI-M group than that in HIBI-F group (t=7.645, P<0.01). Likewise, the residual brain volume in HIBI-M group and HIBI-F group was significantly less than that in control group ((67±4)% and (75±5)% vs. 100%, F=406.122, P<0.01), and the residual brain volume in HIBI-M group was significantly less than that in HIBI-F group (t=-5.281, P<0.01).@*Conclusions@#Male neonatal rats are more vulnerable to HIBI and have severer subsequent brain injury and hemiplegia. Different treatment strategies for HIBI patients of different sexes should be developed.