Germinal Matrix-Intraventricular Hemorrhage of the Preterm Newborn and Preclinical Models: Inflammatory Considerations

Atienza-Navarro, Isabel; Alves-Martínez, Pilar; Lubián‐López, Simón Pedro; García-Alloza, Mónica

doi:10.3390/ijms21218343

Cited by 29 publications

(25 citation statements)

References 157 publications

(455 reference statements)

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“…In turn, this increases the risk of developing brain injury, cerebral palsy, and neurodevelopmental delay [ 75 , 76 ]. Other potential nonspecific causes of perinatal neuroinflammation include intraventricular hemorrhage and cerebrospinal fluid circulation disorders such as post-hemorrhagic hydrocephalus, which are major complications of prematurity and closely associated with white matter injury and neurological disability [ 77 , 78 , 79 ]. For example, preterm infants with post-hemorrhagic ventricular dilatation were reported to show a marked and prolonged elevation in proinflammatory cytokines in the cerebrospinal fluid [ 80 ] and elevated microglial activation and cytokine release in the white matter [ 81 ].…”

Section: Causes Of Perinatal Neuroinflammationmentioning

confidence: 99%

Anti-Inflammatory Therapies for Treatment of Inflammation-Related Preterm Brain Injury

Prasad

Gunn

Davidson

et al. 2021

IJMS

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Despite the prevalence of preterm brain injury, there are no established neuroprotective strategies to prevent or alleviate mild-to-moderate inflammation-related brain injury. Perinatal infection and inflammation have been shown to trigger acute neuroinflammation, including proinflammatory cytokine release and gliosis, which are associated with acute and chronic disturbances in brain cell survival and maturation. These findings suggest the hypothesis that the inhibition of peripheral immune responses following infection or nonspecific inflammation may be a therapeutic strategy to reduce the associated brain injury and neurobehavioral deficits. This review provides an overview of the neonatal immunity, neuroinflammation, and mechanisms of inflammation-related brain injury in preterm infants and explores the safety and efficacy of anti-inflammatory agents as potentially neurotherapeutics.

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Section: Causes Of Perinatal Neuroinflammationmentioning

confidence: 99%

Anti-Inflammatory Therapies for Treatment of Inflammation-Related Preterm Brain Injury

Prasad

Gunn

Davidson

et al. 2021

IJMS

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“…GM‐IVH‐induced neuroinflammation is one of the most relevant pathological features associated with brain injury to the white matter that may contribute to long‐term neurological complications 60 . Many of the animal models of GM‐IVH are associated with an inflammatory response such as increased neutrophil infiltration, activated microglia and gliosis 61 . Interestingly, pericytes have been reported to regulate immune responses in the central nervous system 16,62 .…”

Section: Discussionmentioning

confidence: 99%

Pericyte dynamics in the mouse germinal matrix angiogenesis

et al. 2022

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Germinal matrix-intraventricular hemorrhage (GM-IVH) is the most devastating neurological complication in premature infants. GM-IVH usually begins in the GM, a highly vascularized region of the developing brain where glial and neuronal precursors reside underneath the lateral ventricular ependyma. Previous studies using human fetal tissue have suggested increased angiogenesis and paucity of pericytes as key factors contributing to GM-IVH pathogenesis. Yet, despite its relevance, the mechanisms underlying the GM vasculature's susceptibility to hemorrhage remain poorly understood. To gain better understanding on the vascular dynamics of the GM, we performed a comprehensive analysis of the mouse GM vascular endothelium and pericytes during development. We hypothesize that vascular development of the mouse GM will provide a good model for studies of human GM vascularization and provide insights into the role of pericytes in GM-IVH pathogenesis. Our findings show that the mouse GM presents significantly greater vascular area and vascular branching compared to the developing cortex (CTX). Analysis of pericyte coverage showed abundance in PDGFRβpositive and NG2-positive pericyte coverage in the GM similar to the developing CTX. However, we found a paucity in Desmin-positive pericyte coverage of the GM vasculature. Our results underscore the highly angiogenic nature of the GM and reveal that pericytes in the developing mouse GM exhibit distinct phenotypical and likely functional characteristics compared to other brain regions which might contribute to the high susceptibility of the GM vasculature to hemorrhage.

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“…A population-based case–control study found associations with intrapartum variables such as difficult fetal transition and being small for gestational age[ 13 ]. There are biologically plausible explanations for the adverse effects of UCM in preterm infants related to the fragile germinal matrix[ 14 ]. Premature infants lack adequate cerebral autoregulation compared with mature infants[ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Neonatal hemorrhage stroke and severe coagulopathy in a late preterm infant after receiving umbilical cord milking: A case report

Lü¹,

Zhiqun²

2022

WJCC

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BACKGROUND Umbilical cord milking (UCM) is an alternative placental transfusion method for delayed umbilical cord clamping in routine obstetric practice, allowing prompt resuscitation of an infant. Thus, UCM has been adopted at some tertiary neonatal centers for preterm infants to enhance placental-to-fetal transfusion. It is not suggested for babies less than 28 wk of gestational age because it is associated with severe brain hemorrhage. For late preterm or term infants who do not require resuscitation, cord management is recommended to increase iron levels and prevent the development of iron deficiency anemia, which is associated with impaired motor development, behavioral problems, and cognitive delays. Concerns remain about whether UCM increases the incidence of intraventricular hemorrhage. However, there are very few reports of late preterm infants presenting with neonatal hemorrhage stroke (NHS) and severe coagulopathy after receiving UCM. Here, we report a case of a late preterm infant born at 34 wk of gestation. She abruptly deteriorated, exhibiting signs and symptoms of NHS and severe coagulopathy after receiving UCM on the first day of life. CASE SUMMARY A female preterm infant born at 34 wk of gestation received UCM after birth. She was small for her gestational age and described as vigorous with Apgar scores of 9 and 10 at one minute and five minutes of life, respectively. After hospitalization in the neonatal intensive care unit, she showed hypoglycemia and metabolic acidosis. The baby was administered glucose and sodium bicarbonate infusions. Intramuscular vitamin K1 was also used to prevent vitamin K deficiency. The baby developed umbilical cord bleeding and gastric bleeding on day 1 of life; a physical examination showed bilateral conjunctival hemorrhage, and a blood test showed thrombocytopenia, prolonged prothrombin time, prolonged activated partial thromboplastin time, low fibrinogen, raised D-dimer levels and anemia. A subsequent cranial ultrasound and computed tomography scan showed a left parenchymal brain hemorrhage with extension into the ventricular and subarachnoid spaces. The patient was diagnosed with NHS in addition to disseminated intravascular coagulation (DIC). Fresh frozen plasma (FFP) and prothrombin complex concentrate were given for coagulopathy. Red blood cell and platelet transfusions were provided for thrombocytopenia and anemia. A bolus of midazolam, intravenous calcium and phenobarbital sodium were administered to control seizures. The baby’s clinical condition improved on day 5 of life, and the baby was hospitalized for 46 d and recovered well without seizure recurrence. Our case report suggests that preterm infants who receive UCM should undergo careful clinical assessment for intracranial hemorrhage, NHS and severe coagulopathy that may develop under certain circumstances. Supportive management, such as intensive care, FFP and blood transfusion, is recommended when the development of massive NHS and associated DIC is susp...

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Germinal Matrix-Intraventricular Hemorrhage of the Preterm Newborn and Preclinical Models: Inflammatory Considerations

Cited by 29 publications

References 157 publications

Anti-Inflammatory Therapies for Treatment of Inflammation-Related Preterm Brain Injury

Anti-Inflammatory Therapies for Treatment of Inflammation-Related Preterm Brain Injury

Pericyte dynamics in the mouse germinal matrix angiogenesis

Neonatal hemorrhage stroke and severe coagulopathy in a late preterm infant after receiving umbilical cord milking: A case report

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