[Risk factors for bronchopulmonary dysplasia in twin preterm infants: a multicenter study]. / åŒèƒŽæ—©äº§å„¿æ”¯æ°”ç®¡è‚ºå‘è‚²ä¸è‰¯å±é™©å› ç´ åˆ†æžï¼šä¸€é¡¹å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To investigate the risk factors for bronchopulmonary dysplasia (BPD) in twin preterm infants with a gestational age of <34 weeks, and to provide a basis for early identification of BPD in twin preterm infants in clinical practice. METHODS: A retrospective analysis was performed for the twin preterm infants with a gestational age of <34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020. According to their conditions, they were divided into group A (both twins had BPD), group B (only one twin had BPD), and group C (neither twin had BPD). The risk factors for BPD in twin preterm infants were analyzed. Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins. RESULTS: A total of 904 pairs of twins with a gestational age of <34 weeks were included in this study. The multivariate logistic regression analysis showed that compared with group C, birth weight discordance of >25% between the twins was an independent risk factor for BPD in one of the twins (OR=3.370, 95%CI: 1.500-7.568, P<0.05), and high gestational age at birth was a protective factor against BPD (P<0.05). The conditional logistic regression analysis of group B showed that small-for-gestational-age (SGA) birth was an independent risk factor for BPD in individual twins (OR=5.017, 95%CI: 1.040-24.190, P<0.05). CONCLUSIONS: The development of BPD in twin preterm infants is associated with gestational age, birth weight discordance between the twins, and SGA birth.

Efficacy of inhaled nitric oxide in preterm infants ≤ 34 weeks: a systematic review and meta-analysis of randomized controlled trials.

Background: The effect of inhaled nitric oxide (iNO) in neonates >34 weeks on improving respiration is well documented. However, the efficacy of iNO in preterm infants ≤34 weeks remains controversial. Objectives: The main purpose of this review is to assess the effectiveness and safety of iNO treatment in preterm infants ≤34 weeks. Search methods: We systematically searched PubMed, Embase and Cochrane Libraries from their inception to 1 June 2023. We also reviewed the reference lists of retrieved studies. Selection criteria: Our study involved randomized controlled trials on preterm infants ≤34 weeks, especially those receiving iNO treatment, and mainly assessed outcomes such as bronchopulmonary dysplasia (BPD) and mortality. Two authors independently reviewed these trials, extracted data, and evaluated study biases. Disagreements were resolved by consensus. We used the GRADE method to assess evidence quality. Results: Our research included a total of 17 studies involving 4,080 neonates and 7 follow-up studies. The synthesis of results showed that in neonates, iNO treatment reduced the incidence of BPD (RR: 0.92; 95% CI: 0.86-0.98). It also decreased the composite outcome of death or BPD (RR: 0.94; 95% CI: 0.90-0.98), without increasing the risk of short-term (such as intraventricular hemorrhage, periventricular leukomalacia) and long-term neurological outcomes (including Bayley mental developmental index <70, cerebral palsy and neurodevelopmental impairment). Furthermore, iNO did not significantly affect other neonatal complications like sepsis, pulmonary hemorrhage, necrotizing enterocolitis, and symptomatic patent ductus arteriosus. Subgroup analysis revealed that iNO significantly reduced BPD incidence in neonates at 36 weeks under specific intervention conditions, including age less than 3 days, birth weight over 1,000 g, iNO dose of 10 ppm or higher, or treatment duration exceeding 7 days (p < 0.05). Conclusion: Inhaled NO reduced the incidence of BPD in neonates at 36 weeks of gestation, and the effect of the treatment depended on neonatal age, birth weight, duration and dose of iNO. Therefore, iNO can be considered a promising treatment for the potential prevention of BPD in premature infants. More data, however, would be needed to support nitric oxide registration in this specific patient population, to minimize its off-label use.

Mothers with hypertensive disorders of pregnancy increased risk of periventricular leukomalacia in extremely preterm or extremely low birth weight infants: A propensity score analysis.

Background: At present, the conclusions about the impact of hypertensive disorders of pregnancy (HDP) on the clinical outcomes of preterm infants are inconsistent. This study used the propensity score matching (PSM) analysis to evaluate the effect of HDP on clinical outcomes of extremely preterm or extremely low birth weight (EP/ELBW) infants. Methods: Retrospective analysis was performed on the EP/ELBW infants discharged from 26 tertiary neonatal intensive care units or died during hospitalization from 2008 to 2017, who were divided into HDP group and non-HDP group. The six covariates including sex, gestational age, birth weight, twin or multiple pregnancy, antenatal steroids administration, and conception method were matched through the PSM method at a ratio of 1:1. The survival rate at discharge and the major clinical complications were compared between the two groups. Results: After matching the six covariates, compared with the non-HDP group, there was no significant difference in the survival rate at discharge (64 vs. 63.2%, p > 0.05), the incidence of bronchopulmonary dysplasia (BPD) or moderate to severe BPD in the HDP group (58.3 vs. 54.9%, p > 0.05; 5.2 vs. 6.2%, p > 0.05). The incidence of periventricular leukomalacia (PVL) in the HDP group was significantly increased (5.7 vs. 1.9%, p < 0.05). Conclusions: HDP increased the risk of PVL in EP/ELBW infants, but had no significant effect on the survival rate at discharge, or the occurrence of other complications.

[Sex differences in clinical outcomes of extremely preterm infants/extremely low birth weight infants: a propensity score matching study]. / è¶ æ—©äº§å„¿/è¶ ä½Žå‡ºç”Ÿä½“é‡å„¿ä¸´åºŠç»“å±€çš„æ€§åˆ«å·®å¼‚ï¼šä¸€é¡¹å€¾å‘æ€§è¯„åˆ†åŒ¹é ç ”ç©¶.

OBJECTIVES: To study the effect of sex on the clinical outcome of extremely preterm infants (EPIs)/extremely low birth weight infants (ELBWIs) by propensity score matching. METHODS: A retrospective analysis was performed for the medical data of 731 EPIs or ELBWIs who were admitted from January 1, 2011 to December 31, 2020. These infants were divided into two groups: male and female. A propensity score matching analysis was performed at a ratio of 1:1. The matching variables included gestational age, birth weight, percentage of withdrawal from active treatment, percentage of small-for-gestational-age infant, percentage of use of pulmonary surfactant, percentage of 1-minute Apgar score ≤3, percentage of mechanical ventilation, duration of mechanical ventilation, percentage of antenatal use of inadequate glucocorticoids, and percentage of hypertensive disorders in pregnancy. The two groups were compared in the incidence rate of main complications during hospitalization and the rate of survival at discharge. RESULTS: Before matching, compared with the female group, the male group had significantly higher incidence rates of neonatal respiratory distress syndrome, bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, and patent ductus arteriosus (P<0.05), while after matching, the male group only had a significantly higher incidence rate of BPD than the female group (P<0.05). There was no significant difference in the rate of survival at discharge between the two groups before and after matching (P>0.05). CONCLUSIONS: Male EPIs/ELBWIs have a higher risk of BPD than female EPIs/ELBWIs, but male and female EPIs/ELBWIs tend to have similar outcomes.

Increased Risk for Respiratory Complications in Male Extremely Preterm Infants: A Propensity Score Matching Study.

Background: Many factors can affect the clinical outcome of extremely premature infants (EPIs), but the effect of sex is paradoxical. This study used propensity score matching to adjust baseline information to reassess the clinical outcome of EPIs based on sex. Methods: A retrospective analysis was performed on EPIs admitted in the Department of Neonatology of the Third Affiliated Hospital of Guangzhou Medical University from 2011 to 2020. A propensity score matching (PSM) analysis was used to adjust the confounding factors including gestational age, birth weight, 1-minute Apgar score ≤ 3, withholding or withdrawing life-sustaining treatment(WWLST), mechanical ventilation, duration of mechanical ventilation, the mother with advanced age (≥35 years old), complete-course antenatal steroid therapy and hypertensive disorders of pregnancy. The survival rate at discharge and the incidence of major complications were evaluated between the male and female groups. Results: A total of 439 EPIs were included, and 240 (54.7%) infants were males. After matching the nine confounding factors, 148 pairs of infants were finally enrolled. There was no significant difference in the survival rate at discharge, as well as the mortality of activating treatment or WWLST between the two groups (all P>0.05). However, the incidence of respiratory distress syndrome, bronchopulmonary dysplasia (BPD), and moderate to severe BPD in the male group was significantly increased (all P<0.01), especially at birth weight between 750 and 999 grams. Conclusions: The male EPIs have a higher risk of respiratory complications than females, particularly at 750 to 999 grams of birth weight.

Incidence of extrauterine growth retardation and its risk factors in very preterm infants during hospitalization: a multicenter prospective study. / ä½é™¢æžæ—©äº§å„¿å®«å¤–ç”Ÿé•¿è¿Ÿç¼“åŠç›¸å ³å› ç´ çš„å¤šä¸­å¿ƒå‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS: It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.

Clinical treatment outcomes and their changes in extremely preterm twins: a multicenter retrospective study in Guangdong Province, China. / è¶ æœªæˆç†ŸåŒèƒŽå„¿ä¸´åºŠæ•‘æ²»ç»“å±€åŠå˜åŒ–åˆ†æžï¼šä¸€é¡¹å¹¿ä¸œçœå¤šä¸­å¿ƒå›žé¡¾æ€§ç ”ç©¶.

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS: There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.

Efficacy and safety of surfactant administration via thin catheter in preterm infants with neonatal respiratory distress syndrome: A systematic review and meta-analysis.

OBJECTIVE: The efficacy and safety of surfactant administration via thin catheter in preterm infants with neonatal respiratory distress syndrome (NRDS) was investigated. METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were searched to identify randomized controlled trials (RCTs) that comparing thin catheter technique with intubation for surfactant delivery in preterm infants with NRDS. RESULTS: Thirteen RCTs (1931 infants) were included in the meta-analysis. The use of thin catheter technique decreased the incidences of bronchopulmonary dysplasia (BPD), pneumothorax, and hemodynamically significant patent ductus arteriosus (hsPDA) (risk ratio [RR]: 0.59, 95% confidence interval [CI]: 0.46-0.75, p < .0001; RR: 0.60, 95% CI: 0.39-0.93, p = .02 and RR: 0.88, 95% CI: 0.78-1.00, p = .04, respectively). In addition, infants in the intervention group required less mechanical ventilation within 72 h of life or during hospitalization (RR: 0.60, 95% CI: 0.48-0.75, p < .00001 and RR: 0.64, 95% CI: 0.49-0.82, p = .0005, respectively) compared with infants in the control group. However, the rate of surfactant reflux was higher in the intervention group than that in the control group (RR: 2.12, 95% CI: 1.37-3.29, p = .0008). There were no significant differences in mortality and other outcomes between the two groups. CONCLUSION: The administration of surfactant via thin catheter could lower the requirement for mechanical ventilation, and decrease the incidence of BPD, pneumothorax, and hsPDA.

Umbilical Cord Blood-Derived Exosomes From Very Preterm Infants With Bronchopulmonary Dysplasia Impaired Endothelial Angiogenesis: Roles of Exosomal MicroRNAs.

Premature infants have a high risk of bronchopulmonary dysplasia (BPD), which is characterized by abnormal development of alveoli and pulmonary vessels. Exosomes and exosomal miRNAs (EXO-miRNAs) from bronchoalveolar lavage fluid are involved in the development of BPD and might serve as predictive biomarkers for BPD. However, the roles of exosomes and EXO-miRNAs from umbilical cord blood of BPD infants in regulating angiogenesis are yet to be elucidated. In this study, we showed that umbilical cord blood-derived exosomes from BPD infants impaired angiogenesis in vitro. Next-generation sequencing of EXO-miRNAs from preterm infants without (NBPD group) or with BPD (BPD group) uncovered a total of 418 differentially expressed (DE) EXO-miRNAs. These DE EXO-miRNAs were primarily enriched in cellular function-associated pathways including the PI3K/Akt and angiogenesis-related signaling pathways. Among those EXO-miRNAs which are associated with PI3K/Akt and angiogenesis-related signaling pathways, BPD reduced the expression of hsa-miR-103a-3p and hsa-miR-185-5p exhibiting the most significant reduction (14.3% and 23.1% of NBPD group, respectively); BPD increased hsa-miR-200a-3p expression by 2.64 folds of the NBPD group. Furthermore, overexpression of hsa-miR-103a-3p and hsa-miR-185-5p in normal human umbilical vein endothelial cells (HUVECs) significantly enhanced endothelial cell proliferation, tube formation, and cell migration, whereas overexpressing hsa-miR-200a-3p inhibited these cellular responses. This study demonstrates that exosomes derived from umbilical cord blood of BPD infants impair angiogenesis, possibly via DE EXO-miRNAs, which might contribute to the development of BPD.

Omega-3 Long-chain Polyunsaturated Fatty Acids for Bronchopulmonary Dysplasia: A Meta-analysis.

CONTEXT: Previous studies have suggested that intervention with omega-3 long-chain polyunsaturated fatty acids (N-3 LCPUFAs), especially docosahexaenoic acid, can reduce the incidence of bronchopulmonary dysplasia (BPD) in preterm infants. However, conflicting results have been reported. OBJECTIVE: We conducted this meta-analysis to investigate the effect of intervention with N-3 LCPUFAs on the incidence of BPD in preterm infants. DATA SOURCES: PubMed, Embase, and the Cochrane Library were searched for articles published from database inception to October 1, 2018. STUDY SELECTION: We included randomized controlled trials (RCTs) in which the effect of intervention with N-3 LCPUFAs on the incidence of BPD was examined. DATA EXTRACTION: Two independent authors conducted the literature search and data extraction. The risk ratio was determined, and subgroup analyses were performed. RESULTS: After applying the inclusion criteria, 14 RCTs with 3531 preterm infants were included in the study. Intervention with N-3 LCPUFAs revealed no significant effect on the incidence of BPD in preterm infants (risk ratio: 0.99; 95% confidence interval: 0.84-1.18; Z = 0.08; P = .93). Our secondary subgroup analysis, which was stratified by gestational age, birth weight, dosage of docosahexaenoic acid, and duration of intervention, also revealed no significant effects. LIMITATIONS: The populations, protocols, and pharmaceutical ingredients of N-3 LCPUFAs vary among the included RCTs. CONCLUSIONS: The results of our meta-analysis indicate that intervention with N-3 LCPUFAs cannot prevent BPD in preterm infants. These findings provide no support for intervention with N-3 LCPUFAs in preterm infants.

Different concentrations of docosahexanoic acid supplement during lactation result in different outcomes in preterm Sprague-Dawley rats.

PROPOSE: In this study, we evaluated the effects of different concentrations of docosahexanoic acid (DHA) supplement on preterm Sprague-Dawley rat pups, and in parallel, measured the phosphorylation activity of the mTOR pathway in the hippocampal CA1 area. METHODS: Preterm Sprague-Dawley rat pups were randomly assigned to experimental groups which included; a sufficient DHA group (100 mg/kg/day); an enriched DHA group (300 mg/kg/day); an excess DHA group (800 mg/kg/day); and a deficient DHA group (normal saline gavage 0.1 ml/10 g). Body weight (g) was measured at days 1/7/14/21/28/42, respectively. Spatial learning and memory were also tested using the Morris water maze at week 6 (day 42). Finally, activation of the mTOR signaling pathway in hippocampal CA1 area were evaluated by western blotting. RESULTS: Postnatal sufficient/enriched docosahexanoic acid supplement ameliorated body weight restriction, spatial learning and memory restriction, and decreased phosphorylation of AKT, mTOR, P70S6K1, and 4EBP1 in hippocampal CA1 area. Furthermore, excess docosahexanoic acid supplement impeded weight gain and spatial learning and memory, perturbed serum unsaturated fatty acid, and downregulated phosphorylation of AKT, mTOR, P70S6K1, and 4EBP1 in hippocampal CA1 area. CONCLUSION: Postnatal sufficient/enriched DHA supplement ameliorated growth and spatial learning and memory impairment and upregulated the mTOR pathway in preterm pups, although excessive DHA supplement did not have any beneficial effects.

Bovine Surfactant Replacement Therapy in Neonates of Less than 32 Weeks' Gestation: A Multicenter Controlled Trial of Prophylaxis versus Early Treatment in China--a Pilot Study.

BACKGROUND: A domestic surfactant preparation has been used in China for a number of years. However, as for other surfactant preparations, there is debate among neonatologists regarding the optimal dose, mode of administration, and the best time of intervention. OBJECTIVE: To evaluate whether prophylactic administration of surfactant is superior to early treatment in preterm infants < 32 weeks with a high risk of respiratory distress syndrome (RDS). METHODS: We prospectively compared small premature infants (< 32 weeks) receiving 70 mg/kg bovine surfactant within 30 minutes after birth (prophylactic group, N = 116) with infants who received surfactant therapy for established RDS (early treatment group, N = 91). The primary outcome assessed was the incidence of RDS. The secondary outcomes assessed were severity of RDS, mortality, and bronchopulmonary dysplasia morbidity. RESULTS: Compared with the early treatment group, the prophylactic group had a significantly better PaO2 (at 1 hour, 4 hours, and 12 hours postdose, respectively), better a/APO2 (at 1 hour, 4 hours, 12 hours, and 24 hours postdose, respectively), lower PaCO2 (at 1 hour postdose), and a significantly decreased need for mean airway pressure (MAP) and FiO2 on ventilation (p < 0.05). The prophylactic group had shorter durations for mechanical ventilation and supplemental oxygen compared with the early treatment group (p < 0.01 and p < 0.05, respectively). The incidence of RDS was comparable between the groups; however, the prophylactic group had a significantly lower incidence of severe RDS and significantly lower rate of repeated doses of surfactant than the early treatment group (p < 0.05). The incidences of bronchopulmonary dysplasia and patent ductus arteriosus were also lower in the prophylactic group than the early treatment group (p < 0.05). The two groups were comparable in mortality rate. CONCLUSION: In preterm infants under 32 weeks' gestation, prophylactic use of a domestic surfactant preparation is better than early surfactant treatment in improving pulmonary status and in decreasing the incidence of severe RDS and duration on mechanical ventilation.

[Comparative analysis of risk factors for preterm and small-for-gestational-age births].

OBJECTIVE: To compare the risk factors between preterm and small-for-gestational-age (SGA) births. METHODS: A total of 1 270 newborns who had no obstetric risk factors or maternal diseases were enrolled in this study. Their mothers' stature, body weight, passive smoking, and history of abnormal pregnancy were investigated using the self-designed questionnaire. The infants were divided into four groups: preterm, appropriate-for-gestational-age (AGA), SGA, and term infants. Multivariate logistic regression analysis was performed to compare the risk factors between preterm and SGA births. RESULTS: A weight gain less than 9 kg during pregnancy increased the risks of preterm (OR=1.63, 95% CI: 1.12-2.07) and SGA (OR=1.92, 95% CI: 1.56-2.58). The histories of abortion (OR=1.46, 95% CI: 1.09-1.93) and preterm birth (OR=2.63, 95% CI: 1.81-3.92) were independent risk factors for preterm births, while low pre-pregnancy body mass index (<18.5) (OR=2.16, 95% CI: 1.53-3.16), short stature (<1.55 m) (OR=2.46, 95% CI: 1.78-3.48), and passive smoking (OR=2.24, 95% CI: 1.65-2.98) were independent risk factors for SGA births. CONCLUSIONS: Due to different risk factors between preterm and SGA births, specific preventive measures should be taken pertinently to reduce the incidence of the two bad pregnancy outcomes.

Toll-like receptor 4 is associated with seizures following ischemia with hyperglycemia.

Seizures are a common sequel of cerebral ischemia, and hyperglycemia markedly increases the onset of seizures following an ischemic insult. However, the underlying mechanism of seizures is unclear. The toll-like receptor 4 (TLR4) pathway is known to be involved in temporal lobe epilepsy. The present study investigated the potential involvement of TLR4 in the pathogenesis of seizures following cerebral ischemia with hyperglycemia. Fifteen minutes of global ischemia was produced in adult Wistar rats using a 4-vessel occlusion method. Hyperglycemia was induced via an intraperitoneal injection of glucose 15 min prior to ischemia. We determined that 56.7% of the hyperglycemic rats, but none of the normoglycemic rats, developed tonic-clonic seizures within 12h after ischemia. TLR4 was mildly expressed in a few cells in the control hippocampus, primarily in interneurons, and was localized in the cytoplasm. The TLR4-positive cells were significantly increased 3-12h after ischemia. In the hyperglycemic ischemia group, TLR4-positive cells were further increased in quantity and intensity, with a peak at 3h after ischemia relative to the normoglycemic group. There was no difference in the expression of TLR4 between the hyperglycemic ischemia and LPS groups or between the hyperglycemic non-ischemia and control groups. Western blot analysis consistently exhibited an increase in TLR4 protein levels in the CA3 region 3h after hyperglycemic ischemia. High mobility group box 1 (HMGB1) (an endogenous ligand of TLR4) was localized in the nucleus of neuronal cells throughout the hippocampus in the control animals. We observed a dramatic decrease in HMGB1 immunostaining at 3h after hyperglycemic ischemia that gradually returned to control levels. These results suggest that the TLR4 pathway is associated with seizures following global ischemia with hyperglycemia, which provides a new direction for the study of the pathogenesis of seizures that result from hyperglycemic ischemia.