Prolonged microgliosis in the rhesus monkey central nervous system after traumatic brain injury.
Impaired fine motor functions after traumatic brain injury (TBI) in humans and non-human primates often continue to improve months after injury. To initiate a series of studies in the primate model designed to investigate possible involvement of microglia/macrophage in the long-term recovery processes, changes in these cells were studied in the rhesus monkey central nervous system at 1, 6, and 12 months after a combined unilateral lesion of the arm area of the primary motor cortex and arm area of the lateral premotor cortex. Immunohistological studies showed profound CD68 immunoreactivity in the lesion area and the contralateral lateral corticospinal tract in the spinal cord at all time points, demonstrating that microglia/macrophage remain reactive at the sites of injury and axonal degeneration/survival for at least 12 months. We also observed marked increases in brain-derived neurotrophic factor (BDNF) and its receptor subtypes, TrkB[gp145] and TrkB[TK-], around the cortical lesion site after 6-month survival. Similar increases were also observed in the spinal cord, although it was less apparent for TrkB[gp145]. Double-labeling revealed that a subpopulation of CD68-immunoreacitve microglia/macrophage co-expressed BDNF in the cortex and spinal cord, and also TrkB[gp145] or TrkB[TK-] in the spinal cord. In contrast, cytokine expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) at these time intervals was less prominent, suggesting that immediate inflammatory responses had subsided. These results demonstrate that microglia/macrophage undergo prolonged activation after TBI in the non-human primate brain and express BDNF and its receptors, suggesting their tropic/trophic roles in the long-term recovery processes.
Nagamoto-Combs
Kumi
K
Department of Pharmacology, Physiology and Therapeutics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota 58202, USA.
McNeal
David W
DW
Morecraft
Robert J
RJ
Combs
Colin K
CK
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001930:Brain Injuries / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002574:Cervical Vertebrae; D005911:Gliosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008253:Macaca mulatta; D008264:Macrophages / Q000473:pathology; D008297:Male; D017628:Microglia / Q000473:pathology; D020813:Receptor, trkB / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB; C067980:CD68 antigen, human; D000097382:CD68 Molecule