PRECIOUS study (PREterm Caesarean/vaginal birth and IVH/OUtcomeS): does mode of birth reduce the risk of death or brain injury in very preterm babies? A cohort and emulated target trial protocol.

INTRODUCTION: Very preterm babies are at risk of poor neurodevelopmental outcomes and death. Intraventricular haemorrhage (IVH) after birth is the most prevalent cause of this. Birth by caesarean section may protect against IVH in very preterm babies, but the evidence is limited. The aim is to identify and obtain the quantitative evidence needed to inform a future definitive clinical trial to determine the optimal mode of delivery in preterm birth. METHODS AND ANALYSIS: We will use three broad workstreams (WS) to answer complementary questions. WSs 1 and 2 involve the analysis of routinely recorded national clinical data held in an established research database. In WS1 (October 2023-March 2024), we will use conventional methods to identify what is needed to undertake a trial: the population of interest, areas of equipoise and a plausible range of effect sizes. In WS2 (April 2024-October 2024), using an emulated target trial framework, we will attempt to make inferences about the treatment effect from such a future trial and will identify potential challenges in recruitment and estimate likely 'intention-to-treat' versus 'per-protocol' profiles; these analyses will also be useful for power calculations for future possible trials. In WS3 (October 2024-March 2025), we will convene a consensus meeting with key stakeholders, supported by a clinical trials unit, to develop a multicentre clinical trial to identify the optimal mode of birth for preterm deliveries. ETHICS AND DISSEMINATION: In this study, we will use deidentified data held in the National Neonatal Research Database (NNRD), an established national population database; parents can opt out of their baby's data being held in the NNRD. HRA/Health and Care Research Wales and National Health Service (NHS) study-specific Research Ethics Committee approval (London-Queen Square Research Ethics Committee) (Ref: 23/LO/0826) ethical approval has been obtained. Key outputs of the PRECIOUS (PREterm Caesarean/vaginal birth and IVH/OUutcomeS) study include the identification of the data, and accordingly of the multidisciplinary team required, to develop, gain funding and complete, a clinical trial to definitively identify the optimal mode of delivery for preterm infants and their mothers.

Asiaticoside protected brain injury in hypertensive intracerebral hemorrhage via activation of the PI3K/AKT pathway.

Hypertensive intracerebral hemorrhage (HICH) is a destructive disease with high mortality, incidence, and disability. Asiaticoside (AC) is a triterpenoid derivative that has demonstrated to exert a protective effect on neuron and blood vessel. To investigate the function and potential mechanism of AC on HICH. Human brain microvascular endothelial cells (hBMECs) were treated with 20 U/mL thrombin for 24 h to establish the HICH model in vitro, and AC with the concentration of 1, 2 and 4 µM were used to incubate hBMECs. The effect and potential mechanism of AC on HICH were investigated by using cell counting kit-8, flow cytometry, tube forming assays, vascular permeability experiments and western blot assays. In vivo, rats were injected with 20 µL hemoglobin with a concentration of 150 mg/mL, and then intragastrically administrated with 1.25, 2.5 and 5 mg/kg AC. Behavioral tests, brain water content measurement, hematoxylin-eosin (HE) staining, terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling assays, and western blot were used to assess the effect and potential mechanism of AC on HICH. AC (at 2 and 4 µM) improved the proliferation, apoptosis, angiogenesis and vascular permeability in thrombin-induced hBMECs (p < 0.05). Besides, AC (2.5 and 5 mg/kg) ameliorated behavioral scores, brain water content, pathological lesion, apoptosis and the expression of vascular permeability-related proteins in rats with HICH (p < 0.05). In addition, AC elevated the expression of PI3K/AKT pathway after HICH both in cell and animal models (p < 0.05). Application of LY294002, an inhibitor of PI3K/AKT pathway, reversed the ameliorative effect of AC on the proliferation, apoptosis, angiogenesis and vascular permeability in thrombin-induced hBMECs (p < 0.05). AC reduced brain damage by increasing the expression of the PI3K/AKT pathway after HICH.

Protective effects of forsythoside A against severe acute pancreatitis- induced brain injury in mice.

OBJECTIVES: This study aimed to evaluate the therapeutic effects of forsythoside A (FA) on brain injury induced by severe acute pancreatitis (SAP) using a murine model. METHODS: Mice were induced with 3.5 % sodium taurocholate to model SAP-induced brain injury (SAP-IBI) and were randomly assigned to four distinct treatment regimens: the SAP-IBI model group (SAP-IBI), low-dose FA treatment group (FA L+SI), middle-dose FA treatment group (FA M+SI), and high-dose FA treatment group (FA H+SI). A sham-operation group (SO) served as a negative control. Serum levels of interleukin-1ß (IL-1ß) and IL-18 were quantified via ELISA, and serum amylase levels were assessed using optical turbidimetry. mRNA expression levels of AIM2, ASC, Caspase-1, and GAPDH in hippocampal brain tissue were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Protein levels of NLRP3, GSDMD, IL-1ß, and IL-18 in hippocampal brain tissue were evaluated using Western blotting. Neurological function in surviving mice was assessed through modified neurological severity scores (mNSS). Transmission electron microscopy (TEM) provided ultrastructural analysis of the hippocampus. Additionally, water content and pathological changes in hippocampal brain tissue were examined 24 hours post-operation, along with other relevant indicators. RESULTS: At 24 hours post-operation, the FA H+SI group exhibited significantly reduced levels of serum amylase, IL-1ß, and IL-18, along with decreased expression of AIM2, ASC, and Caspase-1 mRNA. Furthermore, NLRP3 protein levels, water content, pancreas and hippocampal brain pathological scores, and mNSS were significantly lower compared to the SAP-IBI group (P<0.01). CONCLUSIONS: FA demonstrates protective effects against SAP-IBI in mice, suggesting potential therapeutic benefits.

Investigation of the effects of curcumin and piperine on cyclophosphamide-induced brain injury in rats.

Cyclophosphamide (CP) is an antineoplastic drug widely used in chemotherapy. Curcumin (CUR) and piperine (PP) show a protective effect on neurodegenerative and neurological diseases. This research was designed to measure several biochemical parameters in the brain tissue of CP-applied rats to investigate the impact of combined CUR-PP administration. The study evaluated six groups of eight rats: Group 1 was the control; Groups 2 and 3 were administered 200 or 300 mg/kg CUR-PP via oral gavage; Group 4 received only 200 mg/kg CP on day 1; Groups 5 and 6 received CP + CUR-PP for 7 days. Data from all parameters indicated that CP caused brain damage. Phosphorylated TAU (pTAU), amyloid-beta peptide 1-42 (Aß1-42), glutamate (GLU), and gamma amino butyric acid (GABA) parameters were the same in Groups 4, 5, and 6. On the other hand, 8-hydroxy-2-deoxyguanosine (8-OHdG), nitric oxide (NO), interleukin-6 (IL-6), nuclear factor kappa beta (NF-kß), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-α) levels in the CP + CUR-PP groups were lower than those in the CP group (p < 0.05). However, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) parameters were higher in the CP + CUR-PP groups compared to the CP group (p < 0.05). It is thought that the similarity of Groups 5 and 6 with Group 4 in Aß1-42, pTAU, GLU, and GABA parameters hinder the determination of treatment protection however, they might have a therapeutic effect if the applied dose or study duration were changed. This study attempted to evaluate the effects of a CUR-PP combination on CP-induced brain damage in rats by measuring biochemical parameters and performing histopathological examinations. Based on the findings, this CUR-PP combination could be considered an alternative medicine option in cases with conditions similar to those evaluated in this study.

Jiawei Bai-Hu-decoction ameliorated heat stroke-induced brain injury by inhibiting TLR4/NF-κB signal and mitophagy of glial cell.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei Bai-Hu-Decoction (JWBHD), a prescription formulated with seven traditional Chinese medicinal material has demonstrated clinical efficacy in mitigating brain injury among heat stroke (HS) patients. AIM OF THE STUDY: This study aimed to evaluate the therapeutic efficacy of JWBHD on rat model of HS and to explore its therapeutic mechanisms by integrating network pharmacology and pharmacodynamic methodologies, which major components were analyzed by using UPLC-MS/MS. MATERIALS AND METHODS: The network pharmacology analysis was firstly conducted to predict the potential active ingredients and therapeutic targets of JWBHD. The anti-HS effectiveness of JWBHD was then evaluated on rats experienced HS. Rat brain tissues were harvested for a comprehensive array of experiments, including Western blot, PCR, H&E staining, Nissl staining, ELISA, transmission electron microscope, flow cytometry and immunofluorescence to validate the protective effects of JWBHD against HS-induced brain damage. Furthermore, the inhibitory effects of JWBHD on TLR4/NF-κB signal and mitophagy of glial were further verified on HS-challenged F98 cell line. Finally, the chemical compositions of the water extract of JWBHD were analyzed by using UPLC-MS/MS. RESULTS: Network pharmacology has identified fifty core targets and numerous HS-related signaling pathways as potential therapeutic targets of JWBHD. Analysis of protein-protein interaction (PPI) and GO suggests that JWBHD may suppress HS-induced inflammatory signals. In experiments conducted on HS-rats, JWBHD significantly reduced the core temperature, restored blood pressure and alleviated neurological defect. Furthermore, JWBHD downregulated the counts of white blood cells and monocytes, decreased the levels of inflammatory cytokines such as IL-1ß, IL-6 and TNF-α in peripheral blood, and suppressed the expression of TLR4 and NF-κB in the cerebral cortex of HS-rats. Besides, JWBHD inhibited the apoptosis of cortical cells and mitigated the damage to the cerebral cortex in HS group. Conversely, overactive mitophagy was observed in the cerebral cortex of HS-rats. However, JWBHD restored the mitochondrial membrane potential and downregulated expressions of mitophagic proteins including Pink1, Parkin, LC3B and Tom20. JWBHD reduced the co-localization of Pink1 and GFAP, a specific marker of astrocytes in the cerebral cortex of HS-rats. In addition, the inhibitory effect of JWBHD on TLR4/NF-κB signaling and overactive mitophagy were further confirmed in F98 cells. Finally, UPLC-MS/MS analysis showed that the main components of JWBHD include isoliquiritigenin, liquiritin, dipotassium glycyrrhizinate, ginsenoside Rb1, ginsenoside Re, etc. CONCLUSIONS: JWBHD protected rats from HS and prevented HS-induced damage in the cerebral cortex by suppressing TLR4/NF-κB signaling and mitophagy of glial.

Dietary LPC-Bound n-3 LCPUFA Protects against Neonatal Brain Injury in Mice but Does Not Enhance Stem Cell Therapy.

Neonatal hypoxic-ischemic (HI) brain injury is a prominent cause of neurological morbidity, urging the development of novel therapies. Interventions with n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) and mesenchymal stem cells (MSCs) provide neuroprotection and neuroregeneration in neonatal HI animal models. While lysophosphatidylcholine (LPC)-bound n-3 LCPUFAs enhance brain incorporation, their effect on HI brain injury remains unstudied. This study investigates the efficacy of oral LPC-n-3 LCPUFAs from Lysoveta following neonatal HI in mice and explores potential additive effects in combination with MSC therapy. HI was induced in 9-day-old C57BL/6 mice and Lysoveta was orally supplemented for 7 subsequent days, with or without intranasal MSCs at 3 days post-HI. At 21-28 days post-HI, functional outcome was determined using cylinder rearing, novel object recognition, and open field tasks, followed by the assessment of gray (MAP2) and white (MBP) matter injury. Oral Lysoveta diminished gray and white matter injury but did not ameliorate functional deficits following HI. Lysoveta did not further enhance the therapeutic potential of MSC therapy. In vitro, Lysoveta protected SH-SY5Y neurons against oxidative stress. In conclusion, short-term oral administration of Lysoveta LPC-n-3 LCPUFAs provides neuroprotection against neonatal HI by mitigating oxidative stress injury but does not augment the efficacy of MSC therapy.

Mitigating radiation-induced brain injury via NLRP3/NLRC4/Caspase-1 pyroptosis pathway: Efficacy of memantine and hydrogen-rich water.

Radiation-induced brain injury (RIBI) is a significant challenge in radiotherapy for head and neck tumors, impacting patients' quality of life. In exploring potential treatments, this study focuses on memantine hydrochloride and hydrogen-rich water, hypothesized to mitigate RIBI through inhibiting the NLRP3/NLRC4/Caspase-1 pathway. In a controlled study involving 40 Sprague-Dawley rats, divided into five groups including a control and various treatment groups, we assessed the effects of these treatments on RIBI. Post-irradiation, all irradiated groups displayed symptoms like weight loss and salivation, with notable variations among different treatment approaches. Particularly, hydrogen-rich water showed a promising reduction in these symptoms. Histopathological analysis indicated substantial hippocampal damage in the radiation-only group, while the groups receiving memantine and/or hydrogen-rich water exhibited significant mitigation of such damage. Molecular studies, revealed a decrease in oxidative stress markers and an attenuated inflammatory response in the treatment groups. Immunohistochemistry further confirmed these molecular changes, suggesting the effectiveness of these agents. Echoing recent scientific inquiries into the protective roles of specific compounds against radiation-induced damages, our study adds to the growing body of evidence on the potential of memantine and hydrogen-rich water as novel therapeutic strategies for RIBI.

The protective effects of Ferrostatin-1 against inflammation-induced preterm birth and fetal brain injury.

INTRODUCTION: Recent studies have suggested the involvement of ferroptosis in preterm birth. Despite compelling evidence, the underlying mechanism remains unknown. This investigation aimed to determine the therapeutic effects of Ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, in preterm birth and fetal brain injury. METHODS: Human placenta samples and clinical data of participants were collected to ascertain whether placental ferroptosis was associated with preterm birth. Lipopolysaccharide (LPS)-induced preterm birth mouse model was used to examine the protective effects of Fer-1 on preterm birth. Fetal brain tissues and offspring mice at 5 and 8 weeks were studied to determine the effects of Fer-1 on the cognitive function of offspring. RESULTS: We examined the mechanism of spontaneous preterm birth and discovered that placental ferroptosis was associated with preterm birth. Fer-1 inhibited preterm birth by ameliorating placental ferroptosis and maternal inflammation, thus improving LPS-induced intrauterine inflammation to maintain pregnancy. Antenatal administration of Fer-1 prevented LPS-induced fetal brain damage in the acute phase and improved long-term neurodevelopmental impairments by improving placental neuroendocrine signaling and maintaining placental function. CONCLUSION: Fer-1 inhibited preterm birth and fetal brain injury by inhibiting maternal inflammation and improving placental function. Our findings provide a novel therapeutic strategy for preterm birth.

Encontro com Especialistas - Estratégias de neuroproteção no recém-nascido pré-termo

Encontro com os Especialistas Sérgio Marba, médico neonatologista do Hospital da Mulher Caism/Unicamp, professor do Departamento de Pediatria da FCM/Unicamp, consultor neonatal e do Método Canguru/MS e membro do Grupo Executivo do Programa de Reanimação Neonatal (PRN/SBP); Mônica Aparecida Pessoto, médica neonatologista do Hospital da Mulher Caism/Unicamp, professora do Departamento de Pediatria da FCM/Unicamp e consultora do Método Canguru/MS; José Paulo de Siqueira Guida, médico obstetra, professor doutor do departamento de tocoginecologia da FCM/Unicamp; Nicole Gianini, médica neonatologista, consultora do Método Canguru/MS, membro do Departamento de Perinatologia da SBP e SOPERJ.

Methylene Blue Pretreatment Protects Against Repeated Neonatal Isoflurane Exposure-Induced Brain Injury and Memory Loss.

Perioperative neurocognitive impairment (PND) is a common medical complication in the postoperative period. General anesthesia through volatile anesthetics poses a high risk of POCD. Moreover, the developing brain is especially vulnerable to anesthesia-induced neurotoxicity. Therefore, finding a practical approach to prevent or alleviate neonatal isoflurane (ISO) exposure-induced brain injury and cognitive decline is essential for reducing medical complications following major surgery during the early postnatal period. Using a repeated neonatal ISO exposure-induced PND rat model, we investigated the effects of methylene blue (MB) pretreatment on repeated neonatal isoflurane exposure-induced brain injury and memory loss. Intraperitoneal injection of low-dose MB (1 mg/kg) was conducted three times 24 h before each ISO exposure. The Barnes maze and novel objection test were conducted to assess learning and memory. Immunofluorescence staining, F-Jade C staining, TUNEL staining, and Western blot analysis were performed to determine mitochondrial fragmentation, neuronal injury, degeneration, and apoptosis. Evans blue extravasation assay, total antioxidant capacity assay, MDA assay kit, and related inflammatory assay kits were used to test blood-brain barrier (BBB) disruption, antioxidant capacity, and neuroinflammation. Behavioral tests revealed that MB pretreatment significantly ameliorated ISO exposure-induced cognitive deficits. In addition, MB pretreatment alleviates neuronal injury, apoptosis, and degeneration. Furthermore, the BBB integrity was preserved by MB pretreatment. Additional studies revealed that ISO-induced excessive mitochondrial fragmentation, oxidative stress, and neuroinflammation were significantly attenuated by MB pretreatment in the PND rat model. Our findings suggest that MB pretreatment alleviates ISO exposure-induced brain injury and memory loss for the first time, supporting MB pretreatment as a promising approach to protect the brain against neonatal ISO exposure-induced postoperative cognitive dysfunction.

Ceftriaxone to prevent early ventilator-associated pneumonia in patients with acute brain injury: a multicentre, randomised, double-blind, placebo-controlled, assessor-masked superiority trial.

BACKGROUND: Patients with acute brain injury are at high risk of ventilator-associated pneumonia (VAP). The benefit of short-term antibiotic prophylaxis remains debated. We aimed to establish the effect of an early, single dose of the antibiotic ceftriaxone on the incidence of early VAP in patients with severe brain injury who required mechanical ventilation. METHODS: PROPHY-VAP was a multicentre, randomised, double-blind, placebo-controlled, assessor-masked, superiority trial conducted in nine intensive care units in eight French university hospitals. We randomly assigned comatose (Glasgow Coma Scale score [GCS] ≤12) adult patients (age ≥18 years) who required mechanical ventilation for at least 48 h after acute brain injury to receive intravenous ceftriaxone 2 g or placebo once within the 12 h following tracheal intubation. Participants did not receive selective oropharyngeal and digestive tract decontamination. The primary outcome was the proportion of patients developing early VAP from the 2nd to the 7th day of mechanical ventilation, confirmed by masked assessors. The analysis was reported in the modified intention-to-treat population, which comprised all randomly assigned patients except those who withdrew or did not give consent to continue and those who did not receive the allocated treatment because they met a criterion for non-eligibility. The trial is registered with ClinicalTrials.gov, NCT02265406. FINDINGS: From Oct 14, 2015, to May 27, 2020, 345 patients were randomly assigned (1:1) to receive ceftriaxone (n=171) or placebo (n=174); 330 received the allocated intervention and 319 were included in the analysis (162 in the ceftriaxone group and 157 in the placebo group). 166 (52%) participants in the analysis were men and 153 (48%) were women. 15 patients did not receive the allocated intervention after randomisation and 11 withdrew their consent. Adjudication confirmed 93 cases of VAP, including 74 early infections. The incidence of early VAP was lower in the ceftriaxone group than in the placebo group (23 [14%] vs 51 [32%]; hazard ratio 0·60 [95% CI 0·38-0·95], p=0·030), with no microbiological impact and no adverse effects attributable to ceftriaxone. INTERPRETATION: In patients with acute brain injury, a single ceftriaxone dose decreased the risk of early VAP. On the basis of our findings, we recommend that an early, single dose of ceftriaxone be included in all bundles for the prevention of VAP in patients with brain injury who require mechanical ventilation. FUNDING: French Ministry of Social Affairs and Health.

Moslosooflavone protects against brain injury induced by hypobaric hypoxic via suppressing oxidative stress, neuroinflammation, energy metabolism disorder, and apoptosis.

OBJECTIVES: To investigate the protect effect of moslosooflavone against brain injury induced by hypobaric hypoxia (HH) in mice. METHODS: Protective effects of moslosooflavone in oxidative stress, neuroinflammation, energy metabolism disorder, and apoptosis were studied in HH-induced brain damage mice. The pathological morphology in the cortex of mice was determined by hematoxylin and eosin staining. The related protein expressions were detected by western blot. KEY FINDINGS: Moslosooflavone improved HH-induced brain histopathological changes, reduced the contents of ROS and MDA, and elevated the levels of antioxidant enzymes and GSH in HH-exposed brains of mice. Moslosooflavone also markedly enhanced the ATPase activities and PK, ATP contents, while reducing LDH activity and the LD, TNF-α, IL-1ß, and IL-6 contents HH-exposed brains of mice. In addition, moslosooflavone notably decreased the expression of HIF-1α, VEGF, Bax, and cleaved caspase-3 dramatically increasing the expression of Bcl-2, Nrf2, and HO­1 in HH-exposed brains of mice. CONCLUSIONS: Our current studies indicate that moslosooflavone protects HH-induced brain injury possibly through alleviating oxidative stress and neuroinflammation, maintaining the balance of energy metabolism, and inhibiting cell apoptosis.

Neuromonitoring of Pediatric and Adult Extracorporeal Membrane Oxygenation Patients: The Importance of Continuous Bedside Tools in Driving Neuroprotective Clinical Care.

Extracorporeal membrane oxygenation (ECMO) is a form of temporary cardiopulmonary bypass for patients with acute respiratory or cardiac failure refractory to conventional therapy. Its usage has become increasingly widespread and while reported survival after ECMO has increased in the past 25 years, the incidence of neurological injury has not declined, leading to the pressing question of how to improve time-to-detection and diagnosis of neurological injury. The neurological status of patients on ECMO is clinically difficult to evaluate due to multiple factors including illness, sedation, and pharmacological paralysis. Thus, increasing attention has been focused on developing tools and techniques to measure and monitor the brain of ECMO patients to identify dynamic risk factors and monitor patients' neurophysiological state as a function in time. Such tools may guide neuroprotective interventions and thus prevent or mitigate brain injury. Current means to continuously monitor and prevent neurological injury in ECMO patients are rather limited; most techniques provide indirect or postinsult recognition of irreversible brain injury. This review will explore the indications, advantages, and disadvantages of standard-of-care, emerging, and investigational technologies for neurological monitoring on ECMO, focusing on bedside techniques that provide continuous assessment of neurological health.

[Oxytocin as a neuroprotective strategy in neonates: concept and preclinical evidence]. / Oxytocine et neuroprotection en période néonatale : évidences conceptuelles et précliniques.

OBJECTIVE: Prematurity and intra-uterine growth retardation are responsible for brain damage associated with various neurocognitive and behavioral disorders in more than 9 million children each year. Most pharmacological strategies aimed at preventing perinatal brain injury have not demonstrated substantial clinical benefits so far. In contrast, enrichment of the newborn's environment appears to have positive effects on brain structure and function, influences newborn hormonal responses, and has lasting neurobehavioral consequences during infancy and adulthood. Oxytocin (OT), a neuropeptide released by the hypothalamus, may represent the hormonal basis for these long-term effects. METHOD: This review of the literature summarizes the knowledge concerning the effect of OT in the newborn and the preclinical data supporting its neuroprotective effect. RESULTS: OT plays a role during the perinatal period, in parent-child attachment and in social behavior. Furthermore, preclinical studies strongly suggest that endogenous and synthetic OT is capable of regulating the inflammatory response of the central nervous system in response to situations of prematurity or more generally insults to the developing brain. The long-term effect of synthetic OT administration during labor is also discussed. CONCLUSION: All the conceptual and experimental data converge to indicate that OT would be a promising candidate for neonatal neuroprotection, in particular through the regulation of neuroinflammation.

Reprimo (RPRM) as a Potential Preventive and Therapeutic Target for Radiation-Induced Brain Injury via Multiple Mechanisms.

Patients receiving cranial radiotherapy for primary and metastatic brain tumors may experience radiation-induced brain injury (RIBI). Thus far, there has been a lack of effective preventive and therapeutic strategies for RIBI. Due to its complicated underlying pathogenic mechanisms, it is rather difficult to develop a single approach to target them simultaneously. We have recently reported that Reprimo (RPRM), a tumor suppressor gene, is a critical player in DNA damage repair, and RPRM deletion significantly confers radioresistance to mice. Herein, by using an RPRM knockout (KO) mouse model established in our laboratory, we found that RPRM deletion alleviated RIBI in mice via targeting its multiple underlying mechanisms. Specifically, RPRM knockout significantly reduced hippocampal DNA damage and apoptosis shortly after mice were exposed to whole-brain irradiation (WBI). For the late-delayed effect of WBI, RPRM knockout obviously ameliorated a radiation-induced decline in neurocognitive function and dramatically diminished WBI-induced neurogenesis inhibition. Moreover, RPRM KO mice exhibited a significantly lower level of acute and chronic inflammation response and microglial activation than wild-type (WT) mice post-WBI. Finally, we uncovered that RPRM knockout not only protected microglia against radiation-induced damage, thus preventing microglial activation, but also protected neurons and decreased the induction of CCL2 in neurons after irradiation, in turn attenuating the activation of microglial cells nearby through paracrine CCL2. Taken together, our results indicate that RPRM plays a crucial role in the occurrence of RIBI, suggesting that RPRM may serve as a novel potential target for the prevention and treatment of RIBI.

Recombinant erythropoietin protective and related effects on brain injury in premature infants.

OBJECTIVE: The aim of this study was to investigate the protective effect of recombinant erythropoietin at different doses on brain injury in premature infants and the related effects on blood routine, liver function, intellectual development, mental development index (MDI), psychomotor development index (PDI), etc. PATIENTS AND METHODS: A total of 120 premature infants were divided into four groups, including experimental group A (n=30), experimental group B (n=30), experimental group C (n=30) and control group (n=30). The experimental group was treated with different doses of recombinant erythropoietin for brain injury protection of premature infants, while the control group with conventional methods. RESULTS: There was no statistical significance in all test indicators of the four groups of patients before the intervention. After the intervention experiment, the S-100B index was p<0.05, and the erythropoietin (EPO) index was p<0.05. In the comparison of IL-6 indicators, the indicators of the experimental group were reduced after the comparison experiment, and there were significant differences, p<0.05. In neonatal behavior evaluation, there was a statistical difference between groups A and B and the control group (p<0.05), and no statistical significance was shown between group C and the control group (p>0.05). In the intelligence test comparison, the F value of the experimental group was 3.113 three months after treatment. After six months, the F value was 3.654. After nine months, the F value was 3.392 with p<0.05. In the comparison of blood routine indicators, the p-values of four indicators between groups were more than 0.05. In the comparison of liver function indexes, the indexes of groups A, B, and C were significantly changed before and after treatment, and the data after treatment were significantly different from those before treatment, p<0.05. In the comparison of development, there were no significant differences observed in the p-values of the two indicators of vigorous exercise and language in the experimental group. CONCLUSIONS: Recombinant erythropoietin has a protective effect on infants with brain injury and can improve the intellectual development of premature infants, but has no significant effect on blood routine indicators. It can effectively improve the MDI, PDI, and related cytokines of premature infants, and has certain significance for the treatment of brain injury.

Prophylactic supplement with melatonin prevented the brain injury after cardiac arrest in rats.

Prophylactic pharmacotherapy for health care in patients with high risk of cardiac arrest (CA) is an elusive and less explored strategy. Melatonin has possibilities used as a daily nutraceutical to trigger the cellular adaptation. We sought to find the effects of long-term daily prophylactic supplement with melatonin on the victim of CA. Rats were divided into sham, CA, and melatonin + CA (Mel + CA) groups. The rats in the Mel + CA group received daily IP injection of melatonin 100 mg/kg for 14 days. CA was induced by 8 min asphyxia and followed by manual cardiopulmonary resuscitation. The endpoint was 24 h after resuscitation. Survival, neurological outcome, and hippocampal mitochondrial integrity, dynamics and function were assessed. Survival was significantly higher in the Mel + CA group than the CA group (81 vs. 42%, P = 0.04). Compared to the CA group, neurological damage in the CA1 region and the level of cytochrome c, cleaved caspase-3 and caspase-9 in the Mel + CA group were decreased (P < 0.05). Mitochondrial function and integrity were protected in the Mel + CA group compared to the CA group, according to the results of mitochondrial swelling, ΔΨm, ROS production, oxygen consumption rate, and respiratory control rate (P < 0.05). Melatonin increased SIRT3 and downregulated acetylated CypD. The mitochondrial dynamics and autophagy were improved in the Mel + CA group (P < 0.05). Long-term daily prophylactic supplement with melatonin buy the time from brain injury after CA.