Function and Biomarkers of the Blood-Brain Barrier in a Neonatal Germinal Matrix Haemorrhage Model

Andersson, Erik Axel; Rocha‐Ferreira, Eridan; Hagberg, Henrik; Mallard, Carina; Ek, C. Joakim

doi:10.3390/cells10071677

Cited by 6 publications

(5 citation statements)

References 41 publications

(55 reference statements)

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“…In this study we used a previously described preterm rat model of GMH in which near-immediate bleeding is caused by collagenase injection in the brain of P5 rat pups. 18 , 32 Saline-injected rat pups were used as controls. At 6 hours after collagenase injection, bleeding was visible on the surface of the brain, while no bleeding was observed on the brain of saline-injected control rats ( Figure 1(b) ).…”

Section: Resultsmentioning

confidence: 99%

Temporal brain transcriptome analysis reveals key pathological events after germinal matrix hemorrhage in neonatal rats

Shi

Nilsson

et al. 2022

J Cereb Blood Flow Metab

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Germinal matrix hemorrhage (GMH) is a common complication in preterm infants and is associated with high risk of adverse neurodevelopmental outcomes. We used a rat GMH model and performed RNA sequencing to investigate the signaling pathways and biological processes following hemorrhage. GMH induced brain injury characterized by early hematoma and subsequent tissue loss. At 6 hours after GMH, gene expression indicated an increase in mitochondrial activity such as ATP metabolism and oxidative phosphorylation along with upregulation of cytoprotective pathways and heme metabolism. At 24 hours after GMH, the expression pattern suggested an increase in cell cycle progression and downregulation of neurodevelopmental-related pathways. At 72 hours after GMH, there was an increase in genes related to inflammation and an upregulation of ferroptosis. Hemoglobin components and genes related to heme metabolism and ferroptosis such as Hmox1, Alox15, and Alas2 were among the most upregulated genes. We observed dysregulation of processes involved in development, mitochondrial function, cholesterol biosynthesis, and inflammation, all of which contribute to neurodevelopmental deterioration following GMH. This study is the first temporal transcriptome profile providing a comprehensive overview of the molecular mechanisms underlying brain injury following GMH, and it provides useful guidance in the search for therapeutic interventions.

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Section: Resultsmentioning

confidence: 99%

Temporal brain transcriptome analysis reveals key pathological events after germinal matrix hemorrhage in neonatal rats

Shi

Nilsson

et al. 2022

J Cereb Blood Flow Metab

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“…A number of studies have reported the neuroprotective effects of Caffeine, and the antipyretic nature of NSAIDs, providing evidence that these drugs easily cross the blood–brain barrier. While blood–brain barrier permeability, as well as the maturation of neuronal cells, tight junctions, and neurochemicals, may play a key role, studies show that exposure to hypoxia causes significant vascular dysfunction and brain injury (Andersson et al, 2021). It is likely that differences in maturation and IH exposure equally contributed to the responses noted in this study.…”

Section: Discussionmentioning

confidence: 99%

Early versus late caffeine and/or non‐steroidal anti‐inflammatory drugs (NSAIDS) for prevention of intermittent hypoxia‐induced neuroinflammation in the neonatal rat

Batool,

Cai,

Aranda

et al. 2024

Intl J of Devlp Neuroscience

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Preterm infants often experience frequent intermittent hypoxia (IH) episodes which are associated with neuroinflammation. We tested the hypotheses that early caffeine and/or non‐steroidal inflammatory drugs (NSAIDs) confer superior therapeutic benefits for protection against IH‐induced neuroinflammation than late treatment. Newborn rats were exposed to IH or hyperoxia (50% O2) from birth (P0) to P14. For early treatment, the pups were administered: 1) daily caffeine (Caff) citrate (Cafcit, 20 mg/kg IP loading on P0, followed by 5 mg/kg from P1‐P14); 2) ketorolac (Keto) topical ocular solution in both eyes from P0 to P14; 3) ibuprofen (Ibu, Neoprofen, 10 mg/kg loading dose on P0 followed by 5 mg/kg/day on P1 and P2); 4) Caff+Keto co‐treatment; 5) Caff+Ibu co‐treatment; or 6) equivalent volume saline (Sal). On P14, animals were placed in room air (RA) with no further treatment until P21. For late treatment, pups were exposed from P0 to P14, then placed in RA during which they received similar treatments from P15‐P21 (Sal, Caff, and/or Keto), or P15‐P17 (Ibu). RA controls were similarly treated. At P21, whole brains were assessed for histopathology, apoptosis, myelination, and biomarkers of inflammation. IH caused significant brain injury and hemorrhage, inflammation, reduced myelination, and apoptosis. Early treatment with Caff alone or in combination with NSAIDs conferred better neuroprotection against IH‐induced damage than late treatment. Early postnatal treatment during a critical time of brain development, may be preferable for the prevention of IH‐induced brain injury in preterm infants.

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“…The resistance between transwell donor chamber and recipient chamber was measured by using a resistance meter. When the resistance value exceeded 200 Ω/cm 2 , the in vitro BBB model was regarded to be successful established [ 45 ].…”

Section: Methodsmentioning

confidence: 99%

Biomimetic GBM-targeted drug delivery system boosting ferroptosis for immunotherapy of orthotopic drug-resistant GBM

Liu

Cheng

et al. 2022

J Nanobiotechnol

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Background Clinical studies have shown that the efficacy of programmed cell death receptor-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors on glioblastoma (GBM) is much lower than what is expected because of the low immunogenicity of GBM. Ferroptosis of cancer cells can induce the maturation of dendritic cells (DC cells) and increase the activity of T cell. The activated T cells release IFN-γ, which subsequently induces the ferroptosis of cancer cells. Thus, the aim of this paper is to set up a new GBM-targeted drug delivery system (Fe3O4-siPD-L1@M-BV2) to boost ferroptosis for immunotherapy of drug-resistant GBM. Results Fe3O4-siPD-L1@M-BV2 significantly increased the accumulation of siPD-L1 and Fe2+ in orthotopic drug-resistant GBM tissue in mice. Fe3O4-siPD-L1@M-BV2 markedly decreased the protein expression of PD-L1 and increased the ratio between effector T cells and regulatory T cells in orthotopic drug-resistant GBM tissue. Moreover, Fe3O4-siPD-L1@M-BV2 induced ferroptosis of GBM cells and maturation of DC cell, and it also increased the ratio between M1-type microglia and M2-type microglia in orthotopic drug-resistant GBM tissue. Finally, the growth of orthotopic drug-resistant GBM in mice was significantly inhibited by Fe3O4-siPD-L1@M-BV2. Conclusion The mutual cascade amplification effect between ferroptosis and immune reactivation induced by Fe3O4-siPD-L1@M-BV2 significantly inhibited the growth of orthotopic drug-resistant GBM and prolonged the survival time of orthotopic drug-resistant GBM mice. Graphical Abstract

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Function and Biomarkers of the Blood-Brain Barrier in a Neonatal Germinal Matrix Haemorrhage Model

Cited by 6 publications

References 41 publications

Temporal brain transcriptome analysis reveals key pathological events after germinal matrix hemorrhage in neonatal rats

Temporal brain transcriptome analysis reveals key pathological events after germinal matrix hemorrhage in neonatal rats

Early versus late caffeine and/or non‐steroidal anti‐inflammatory drugs (NSAIDS) for prevention of intermittent hypoxia‐induced neuroinflammation in the neonatal rat

Biomimetic GBM-targeted drug delivery system boosting ferroptosis for immunotherapy of orthotopic drug-resistant GBM

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