Gender Differences in Neurodevelopmental Outcomes among Full-Term Infants with Intraventricular Hemorrhage

Matijević, Valentina; Barbarić, Bernarda; Kraljević, Marija; Milas, Ivan; Kolak, Juraj

doi:10.20471/acc.2019.58.01.14

Cited by 3 publications

(5 citation statements)

References 18 publications

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“…GM-IVH is one of the most relevant brain complications of the PT (Radic et al, 2015b;Valdez Sandoval et al, 2019), responsible for severe disabilities in the majority of these patients (Segado-Arenas et al, 2017), including cognitive and motor impairments (Morita et al, 2015;He et al, 2019), developmental delay (Bolisetty et al, 2014;Holwerda et al, 2016;Matijevic et al, 2019), or cerebral palsy (Bolisetty et al, 2014;da Silva et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Caffeine Restores Neuronal Damage and Inflammatory Response in a Model of Intraventricular Hemorrhage of the Preterm Newborn

Alves-Martínez

Atienza-Navarro

Vargas-Soria

et al. 2022

Front. Cell Dev. Biol.

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Germinal matrix-intraventricular hemorrhage (GM-IVH) is the most frequent intracranial hemorrhage in the preterm infant (PT). Long-term GM-IVH-associated sequelae include cerebral palsy, sensory and motor impairment, learning disabilities, or neuropsychiatric disorders. The societal and health burden associated with GM-IVH is worsened by the fact that there is no successful treatment to limit or reduce brain damage and neurodevelopment disabilities. Caffeine (Caf) is a methylxanthine that binds to adenosine receptors, regularly used to treat the apnea of prematurity. While previous studies support the beneficial effects at the brain level of Caf in PT, there are no studies that specifically focus on the role of Caf in GM-IVH. Therefore, to further understand the role of Caf in GM-IVH, we have analyzed two doses of Caf (10 and 20 mg/kg) in a murine model of the disease. We have analyzed the short (P14) and long (P70) effects of the treatment on brain atrophy and neuron wellbeing, including density, curvature, and phospho-tau/total tau ratio. We have analyzed proliferation and neurogenesis, as well as microglia and hemorrhage burdens. We have also assessed the long-term effects of Caf treatment at cognitive level. To induce GM-IVH, we have administered intraventricular collagenase to P7 CD1 mice and have analyzed these animals in the short (P14) and long (P70) term. Caf showed a general neuroprotective effect in our model of GM-IVH of the PT. In our study, Caf administration diminishes brain atrophy and ventricle enlargement. Likewise, Caf limits neuronal damage, including neurite curvature and tau phosphorylation. It also contributes to maintaining neurogenesis in the subventricular zone, a neurogenic niche that is severely affected after GM-IVH. Furthermore, Caf ameliorates small vessel bleeding and inflammation in both the cortex and the subventricular zone. Observed mitigation of brain pathological features commonly associated with GM-IVH also results in a significant improvement of learning and memory abilities in the long term. Altogether, our data support the promising effects of Caf to reduce central nervous system complications associated with GM-IVH.

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Section: Discussionmentioning

confidence: 99%

Caffeine Restores Neuronal Damage and Inflammatory Response in a Model of Intraventricular Hemorrhage of the Preterm Newborn

Alves-Martínez

Atienza-Navarro

Vargas-Soria

et al. 2022

Front. Cell Dev. Biol.

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“…GM-IVH can also exceptionally occur in full term newborns and may be due to maternal risk factors [23,35,36] or severe asphyxiation during childbirth [37], accounting for 3-5% of cases (Matijevic et al, 2019). However, in full-term newborn, most GM-IVH originates in the choroid plexus and less frequently in the GM, unlike the PTNB [38].…”

Section: Germinal Matrix-intraventricular Hemorrhagementioning

confidence: 99%

“…In addition, when newborns are separated from their mothers, they do not receive the necessary biological and maternal emotional care, which triggers adverse short and long-term developmental consequences, including structural and functional alterations of brain development and dysregulation of the hypothalamic-pituitary-adrenal axis stress response system [47] among others. Moreover, brain abnormalities are directly related to an increased risk of sensory [7,23,35], cognitive and motor [33,41] impairments. PTNB with severe GM-IVH commonly suffer developmental delay [23,35,48], associated to cerebelum abnormalities [22], as well as a consequent cerebral palsy [7,23].…”

Section: Gm-ivh Neurodevelopmental Disabilitiesmentioning

confidence: 99%

“…Moreover, brain abnormalities are directly related to an increased risk of sensory [7,23,35], cognitive and motor [33,41] impairments. PTNB with severe GM-IVH commonly suffer developmental delay [23,35,48], associated to cerebelum abnormalities [22], as well as a consequent cerebral palsy [7,23]. Previous studies have reported that approximately 10% of PTNB with severe GM-IVH will develop cerebral palsy [49] and these children will frequently suffer spastic dysplasia where both legs are affected [5].…”

Section: Gm-ivh Neurodevelopmental Disabilitiesmentioning

confidence: 99%

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

Atienza-Navarro

Alves-Martínez

Lubián‐López

et al. 2020

IJMS

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The germinal matrix-intraventricular hemorrhage (GM-IVH) is one of the most important complications of the preterm newborn. Since these children are born at a critical time in brain development, they can develop short and long term neurological, sensory, cognitive and motor disabilities depending on the severity of the GM-IVH. In addition, hemorrhage triggers a microglia-mediated inflammatory response that damages the tissue adjacent to the injury. Nevertheless, a neuroprotective and neuroreparative role of the microglia has also been described, suggesting that neonatal microglia may have unique functions. While the implication of the inflammatory process in GM-IVH is well established, the difficulty to access a very delicate population has lead to the development of animal models that resemble the pathological features of GM-IVH. Genetically modified models and lesions induced by local administration of glycerol, collagenase or blood have been used to study associated inflammatory mechanisms as well as therapeutic targets. In the present study we review the GM-IVH complications, with special interest in inflammatory response and the role of microglia, both in patients and animal models, and we analyze specific proteins and cytokines that are currently under study as feasible predictors of GM-IVH evolution and prognosis.

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“…Although a less severe hemorrhage can be asymptomatic, it is considered that they also carry an increased risk of disability ( 7 ). Rarely, GMH-IVH can also occur in term neonates and carries a risk of adverse neurodevelopmental delay ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Higher Frequency of Germinal Matrix-Intraventricular Hemorrhage in Moderate and Late Preterm and Early Term Neonates with Intrauterine Growth Restriction Compared to Healthy Ones

Mileusnić-Milenović¹

2021

ACC

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SUMMARY Germinal matrix-intraventricular brain hemorrhage is mostly found in preterm neonates, but may also occur in term neonates. The aim of this study was to analyze the prevalence and severity of this type of hemorrhage in moderate and late preterm and early term neonates with intrauterine growth restriction. In the prospective analysis, 100 newborns were examined, i.e. 70 with intrauterine growth restriction and 30 as a control group. Study subjects were neonates from 32 0/7 to 38 6/7 gestational weeks. Body weight, body length, head circumference and ponderal index at birth were analyzed. Hemorrhage was assessed by cranial ultrasound using Papile classification. Out of 70 neonates with intrauterine growth restriction, germinal matrix-intraventricular hemorrhage was not found in 36 (51.43%) neonates, 31 (44.29%) had hemorrhage grade 1, and three (4.29%) had hemorrhage grade 2, which was statistically significant (p<0.001) in relation to the control group. There were no neonates with hemorrhage grade 3 or 4. The predominant type of germinal matrix-intraventricular hemorrhage in the intrauterine growth restriction group was hemorrhage grade 1. Germinal matrix-intraventricular hemorrhage was more often present in the intrauterine growth restricted neonates than in the control group.

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Gender Differences in Neurodevelopmental Outcomes among Full-Term Infants with Intraventricular Hemorrhage

Cited by 3 publications

References 18 publications

Caffeine Restores Neuronal Damage and Inflammatory Response in a Model of Intraventricular Hemorrhage of the Preterm Newborn

Caffeine Restores Neuronal Damage and Inflammatory Response in a Model of Intraventricular Hemorrhage of the Preterm Newborn

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

Higher Frequency of Germinal Matrix-Intraventricular Hemorrhage in Moderate and Late Preterm and Early Term Neonates with Intrauterine Growth Restriction Compared to Healthy Ones

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