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Unilateral Pyramidotomy of the Corticospinal Tract in Rats for Assessment of Neuroplasticity-inducing Therapies
Published on: December 15, 2014
Glial reaction after pyramidotomy in mice and rats
Abstract:
Adult mice and rats were sacrificed by perfusion between 2 and 90 days after right pyramidotomy to study the microglial and astroglial response in the brain and spinal cord. The microglia were detected immunohistochemically with OX-42, OX-18 and OX-6 to assess respectively the expression of complement type 3 receptor, and major histocompatibility class I and class II antigens. Cell counting was also carried out in some animals to determine the possible proliferation of glial cells in the corticospinal tract and around layer V neurons in the cerebral cortex. Some operated animals were given rhodamine B isothiocyanate injection to investigate whether macrophages/monocytes could have migrated from the blood stream to the reactive area. The glial response around the cell bodies of layer V neurons in the ipsilateral cerebral cortex did not display any noticeable difference compared with that of the contralateral side and of the cerebral cortex of the sham-operated and normal control animals. In the cervical and lumbar cord segments of the operated animals, reactive microglial cells in the contralateral corticospinal tract appeared as early as 2 days post pyramidotomy (PP) in rats and 4 days PP in mice. Activation of microglial cells lasted up till 35 days PP, showing gradual increase in immunoreactive staining and hypertrophy. After that, the microglial immunoreactivity subsided and the cells assumed normal appearance by 90 days PP. Quantitative analysis showed a marked increase in the number of microglial cells in the contralateral CST up till 60 days PP. In mice, at 6 days PP, astroglial cells were hypertrophic and more intensely stained but showed no increase in number. No noticeable changes were noted in the astroglia of the rats throughout the period studied. Rhodamine-labelled cells were found at the lesion site, but not in layer V of the cerebral cortex, nor in the corticospinal tract. Though different glial reactions in the degenerating corticospinal tract were noted in mice and rats, there was the same apparent lack of glial reaction around the cell bodies of layer V neurons in the two animal species. Such lack of significant glial response is different from the vigorous glial response around the cell bodies of peripherally projecting neurons demonstrated in previous work. The possible mechanisms for such difference and the implication of the difference in axonal regeneration were discussed.
Insights
This study shows that glial cells, specifically microglia, react to corticospinal tract injury in mice and rats, but not around the neurons themselves. This limited glial response may impact axonal regeneration.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- The central nervous system's response to injury involves glial cells, including microglia and astrocytes.
- Understanding glial activation patterns is crucial for studying neural repair and regeneration.
Purpose of the Study:
- To investigate the microglial and astroglial response in the brain and spinal cord following pyramidotomy in adult mice and rats.
- To compare the glial reaction in the corticospinal tract and around layer V neurons.
Main Methods:
- Adult mice and rats underwent pyramidotomy, with tissue analysis at various time points (2-90 days post-operation).
- Immunohistochemistry (OX-42, OX-18, OX-6) was used to detect microglial activation markers.
- Cell counting and rhodamine B isothiocyanate injection were employed to assess glial proliferation and blood-borne cell migration.
Main Results:
- Reactive microglial cells appeared in the contralateral corticospinal tract (CST) within days of pyramidotomy, with activation lasting up to 35 days and increased cell numbers up to 60 days.
- Astroglial cells in mice showed hypertrophy and increased staining but no proliferation; rats showed no significant astroglial changes.
- No significant glial reaction was observed around the cell bodies of layer V neurons in the cerebral cortex in either species.
Conclusions:
- Pyramidotomy induces a transient microglial response within the degenerating corticospinal tract but not around the parent neurons.
- The lack of a robust glial response around layer V neurons differs from responses seen with peripherally projecting neurons.
- This distinct glial reaction may have implications for understanding axonal regeneration after central nervous system injury.

