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A delayed increase in hippocampal proliferation following global asphyxia in the neonatal rat
Arjan Scheepens1, Guido Wassink, Marrit J Piersma
1Department of Pediatrics, GROW Research Institute, Maastricht, The Netherlands. a.scheepens@np.unimaas.nl
Insights
Neonatal brain injury from birth asphyxia specifically increases cell proliferation in the hippocampus during early postnatal development. This localized response suggests a targeted neurogenic repair mechanism, unlike broader central nervous system changes.
Area of Science:
- Neuroscience
- Developmental Biology
- Neurobiology
Background:
- Adult neurogenesis is upregulated after brain injury.
- Postnatal life exhibits significantly higher neurogenesis than the adult central nervous system (CNS).
- The impact of neonatal brain injury on developmental neurogenesis remains poorly understood.
Purpose of the Study:
- To investigate the effects of perinatal birth asphyxia on postnatal cell proliferation.
- To determine if neonatal brain injury influences neurogenesis in specific brain regions.
- To examine the relationship between injury-induced proliferation, hippocampal growth, and corticosterone levels.
Main Methods:
- Utilized a 3H-thymidine tracer study to track cell proliferation.
- Assessed proliferation at multiple time points (2, 5, 8, 11, 15, 21, 28 days) post-injury.
- Measured hippocampal mass and glial fibrillary acidic protein (GFAP) content, alongside corticosterone levels.
Main Results:
- Observed a specific upregulation of proliferation in the injured hippocampus at 5 days post-birth asphyxia.
- Found a corresponding increase in hippocampal mass without alterations in GFAP content.
- Proliferation in the cerebellum, subventricular zone, olfactory bulb, and spinal cord remained unchanged.
- Injury did not affect corticosterone levels.
Conclusions:
- Perinatal asphyxia induces localized, likely neurogenetic, proliferation in the developing hippocampus.
- The observed increase in proliferation is distinct from changes in GFAP content, suggesting a neurogenic response.
- Elevated corticosterone levels at the end of the stress hyporesponsive period are not responsible for the decline in postnatal CNS proliferation.
Abstract:
Adult neurogenesis has been shown to be upregulated following a wide variety of brain injury paradigms. During the first weeks of postnatal life there is around 50 fold more neurogenesis occurring than in the adult CNS, yet little is known regarding the effect of neonatal brain injury on this developmental proliferation. We have investigated the effect of a global perinatal birth asphyxia on postnatal proliferation at 2, 5, 8, 11, 15, 21 and 28 days after birth (injury) using a 3H-thymidine tracer study. We found a specific upregulation of proliferation at 5 days after the injury within the injured hippocampus only, with an associated increase in hippocampal mass and without any changes in GFAP content at any timepoint. Perinatal asphyxia did not alter proliferation within the cerebellum, sub ventricular zone, olfactory bulb, cervical or thoracic spinal cord. Similarly, no changes in corticosterone levels were induced by the injury. Since there were no changes in GFAP content we hypothesize that this increased proliferation is likely neurogenetic, similar to what is seen in the adult brain following injury. Further we show that the dramatic increase in corticosterone at the end of the stress hyporesponsive period is not responsible for the equally dramatic decrease in postnatal proliferation within the CNS.