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Published on: November 20, 2015
Prenatal Systemic Hypoxia-Ischemia and Oligodendroglia Loss in Cerebellum
Penha Cristina Barradas1, Tiago Savignon2,3, Alex C Manhães4
1Depto. Farmacologia e Psicobiologia, Instituto de Biologia-UERJ, Av. 28 de setembro, 87 fds 5° andar, Rio de Janeiro, RJ, 20551-030, Brazil. penhabarradas@gmail.com.
Insights
Hypoxic-ischemic (HI) injury impacts newborns, causing stable rates of birth injury. This study reveals cerebellar damage and delayed myelination in a neonatal HI model, potentially explaining motor deficits.
Area of Science:
- Neuroscience
- Developmental Biology
- Neonatal Research
Background:
- Hypoxic-ischemic (HI) injury remains a significant cause of neonatal death and disability, with birth injury rates unchanged despite medical advancements.
- While neural cell alterations are documented, the cerebellum's role in motor deficits following HI injury requires further investigation.
- Existing animal models, like the one by Robinson et al. (2005), mimic aspects of HI injury but lack detailed cerebellar analysis.
Purpose of the Study:
- To investigate the impact of a specific neonatal hypoxic-ischemic (HI) injury model on cerebellar development and oligodendroglia in the cerebellum.
- To assess the temporal profile of neuroinflammation (iNOS, microgliosis, astrogliosis) in the cerebellum post-HI.
- To evaluate the effects of HI on oligodendrocyte progenitor cells (PDGFRα+) and myelination in the developing cerebellum.
Main Methods:
- Utilized a rodent model of HI injury induced by temporary uterine artery clamping on day 18 of gestation.
- Quantified inducible nitric oxide synthase (iNOS) levels at postnatal day 0 (P0).
- Assessed microgliosis and astrogliosis at P0, P9, and P23.
- Evaluated oligodendrocyte progenitor cell numbers (PDGFRα+) and myelination status at P9.
Main Results:
- Observed increased iNOS levels at P0, indicating early inflammatory response.
- Detected significant microgliosis and astrogliosis at P9 and persistent astrogliosis at P23, confirming ongoing neuroinflammation.
- Found a decrease in PDGFRα+ cells and delayed myelination in the cerebellum of HI-affected animals at P9.
- These findings suggest impaired oligodendrocyte development and myelination in the cerebellum following neonatal HI.
Conclusions:
- Neonatal HI injury induces significant neuroinflammation and disrupts oligodendrocyte progenitor cell development and myelination in the cerebellum.
- The observed cerebellar injury and myelination delay may underlie the motor function deficits seen in survivors of HI.
- This study highlights the cerebellum as a vulnerable target in neonatal HI, providing insights into the mechanisms of motor impairment.
Abstract:
Hypoxic-ischemic (HI) injury is an important cause of death and disabilities. Despite all improvements in neonatal care, the number of children who suffer some kind of injury during birth has remained stable in the last decade. A great number of studies have shown alterations in neural cells and many animal models have been proposed in the last 5 decades. Robinson et al. (2005) proposed an HI model in which the uterine arteries are temporarily clamped on the 18th gestation day. The findings were quite similar to the ones observed in postmortem studies. The white matter is clearly damaged, and a great amount of astrogliosis takes place both in the gray and white matters. Motor changes were also found but no data regarding the cerebellum, an important structure related to motor performance, was presented. Using this model, we have shown an increased level of iNOS at P0 and microgliosis and astrogliosis at P9, and astrogliosis at P23 (up to 4 weeks from the insult). NO is important in migration, maturation, and synaptic plasticity, but in exacerbated levels it may also contribute to cellular and tissue damage. We have also evaluated oligodendroglia development in the cerebellum. At P9 in HI animals, we found a decrease in the number of PDGFRα+ cells and an apparent delay in myelination, suggesting a failure in oligodendroglial progenitors migration/maturation and/or in the myelination process. These results point to an injury in cerebellar development that might help to explain the motor problems in HI.
