Long-term gliosis and molecular changes in the cervical spinal cord of the rhesus monkey after traumatic brain injury
- PMID: 20030560
- PMCID: PMC2867631
- DOI: 10.1089/neu.2009.0966
Long-term gliosis and molecular changes in the cervical spinal cord of the rhesus monkey after traumatic brain injury
Abstract
Recovery of fine motor skills after traumatic brain injury (TBI) is variable, with some patients showing progressive improvements over time while others show poor recovery. We therefore studied possible cellular mechanisms accompanying the recovery process in a non-human primate model system, in which the lateral frontal motor cortex areas controlling the preferred upper limb were unilaterally lesioned, and the animals eventually regained fine hand motor function. Immunohistochemical staining of the cervical spinal cord, the site of compensatory sprouting and degeneration of corticospinal axons, showed profound increases in immunoreactivities for major histocompatibility complex class II molecule (MHC-II) and extracellular signal-regulated kinases (ERK1/2) up to 12 months post lesion, particularly within the lateral corticospinal tract (LCST). Double immunostaining demonstrated that phosphorylated ERK1/2 colocalized within the MCH-II + microglia, suggesting a trophic role of long-term microglia activation after TBI at the site of compensatory sprouting. Active sprouting was observed in the LCST as well as in the spinal gray matter of the lesioned animals, as illustrated by increases in growth associated protein 43. Upregulation of Nogo receptor and glutamate transporter expression was also observed in this region after TBI, suggesting possible mechanisms for controlling aberrant sprouting and/or synaptic formation en route and interstitial glutamate concentration changes at the site of axon degeneration, respectively. Taken together, these changes in the non-human primate spinal cord support a long-term trophic/tropic role for reactive microglia, in particular, during functional and structural recovery after TBI.
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