Abstract

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.

Highlights

  • A preterm newborn (PTNB) is the one born before 37 weeks gestation, considering that a normal gestation lasts for 280 ± 15 days [1]

  • Central nervous system (CNS) immaturity is based, among others, on the fragile vascular structure of germinal matrix (GM), low neuronal migration, poor myelinization of white matter and exponential growth of the grey matter [1]. These limitations result in different types of brain lesions in the PTNB, including white matter injury, intracranial hemorrhages, cerebellar injury [5,15,23,24], periventricular leukomalacia, periventricular hemorrhagic infarction with subsequent posthemorrhagic hydrocephalus [25] or posthemorrhagic ventriculomegaly [21]

  • Previous studies have shown that there are no significant differences in the short term when neurological development and cerebral palsy are compared between low-grade germinal matrix-intraventricular hemorrhage (GM-IVH) and non-GM-IVH controls [36]

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Summary

The preterm newborn

A preterm newborn (PTNB) is the one born before 37 weeks gestation, considering that a normal gestation lasts for 280 ± 15 days [1]. Depending on the gestational age, PTNB can be classified as extremely preterm (

Etiology and Consequences of Prematurity
Neurological Complications of the PTNB
Germinal Matrix-Intraventricular Hemorrhage
GM-IVH Neurodevelopmental Disabilities
GM-IVH Associated Brain Damage
Neuroinflammation and Microglia in the GM-IVH
Animal Models of GM-IVH
Genetically Modified Models
Lesion-Induced Models
Glycerol-Induced GM-IVH in Rabbits
Blood and Blood Derivates-Induced GM-IVH in Rodents
Collagenase-Induced GM-IVH in Rodents
Findings
Neuroinflammation and Microglia in Animal Models of GM-IVH
Full Text
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