Related Experiment Videos
Extension of the critical period for developmental plasticity of the corticospinal pathway
B S Bregman1, E Kunkel-Bagden, M McAtee
1Department of Anatomy and Cell Biology, Georgetown University School of Medicine, Washington, D.C. 2007.
Insights
Transplanting fetal tissue into spinal cord lesions in rats can extend the critical period for corticospinal tract (CST) developmental plasticity, promoting axon growth after injury.
Area of Science:
- Neuroscience
- Developmental Biology
- Regenerative Medicine
Background:
- The corticospinal tract (CST) in rats exhibits extended postnatal development, allowing for significant plasticity after early-life injury.
- Developmental plasticity of the CST is limited by 5-6 days of age, hindering axonal regrowth around lesion sites.
- Understanding factors that prolong this critical period is crucial for therapeutic interventions.
Purpose of the Study:
- To investigate if fetal spinal cord tissue transplantation can extend the critical period for corticospinal pathway developmental plasticity.
- To assess the impact of fetal transplants on corticospinal axon growth following spinal cord injury at different developmental stages.
Main Methods:
- Spinal cord overhemisection was performed in rats at three distinct developmental stages: before axon arrival, after elongation but before synaptogenesis, and after synaptogenesis.
- Anterograde neuronal tracing using horseradish peroxidase was employed 1-9 months post-lesion to evaluate CST pathway growth.
- Labeling patterns were compared between lesioned animals with and without fetal transplants and control animals.
Main Results:
- Fetal tissue transplantation significantly prolonged the critical period for CST developmental plasticity.
- Transplants facilitated CST axon growth across all examined postnatal periods.
- Axons lesioned prior to synaptogenesis showed more substantial growth compared to those injured after synaptogenesis.
Conclusions:
- Environmental factors, such as fetal tissue transplants, can extend the window for developmental plasticity in the CST.
- Both environmental cues and intrinsic neuronal factors interact to modulate the response of immature corticospinal neurons to injury.
- These findings suggest potential therapeutic strategies for promoting neural repair after spinal cord injury.
Abstract:
The corticospinal tract (CST) of the rat undergoes a prolonged period of postnatal development. Lesions of the presumptive CST pathway at birth are followed by the aberrant rerouting of the developing corticospinal axons around the lesion site through adjacent undamaged CNS tissue. This developmental plasticity becomes severely restricted by 5-6 days of age, so the axons are no longer capable of growth around the site of injury. The aim of the current study was to determine whether altering the environment at the site of injury by filling the lesion with transplanted fetal spinal cord tissue could prolong the critical period for developmental plasticity of the corticospinal pathway. The spinal cord was damaged (overhemisection) at three stages in the development of the corticospinal (CS) pathway: 1) prior to the arrival of CS axons, 2) after the axons elongated through the cord but prior to synaptogenesis, and 3) after both axonal elongation and synaptogenesis were completed. One to 9 months later, anterograde neuronal tracing with horseradish peroxidase was used to assess the growth of the corticospinal pathway with or without a fetal transplant at the site of injury, and the pattern of labeling was compared with that observed in adult nonlesioned control animals. Our results indicate that the presence of a transplant prolongs the critical period for developmental plasticity of the CST. Transplants elicited growth of CST axons throughout the postnatal period examined. CST axons damaged prior to synaptogenesis exhibited more robust growth than those lesioned after synaptogenesis had been completed. These results suggest that both environmental and neuronal factors interact to regulate the response of immature CS neurons to injury.