Cited by 157Traumatic Brain Injury and Neurovascular DisturbancesNeuroinflammation and Neurodegeneration MechanismsTraumatic Brain Injury Research

Prolonged Microgliosis in the Rhesus Monkey Central Nervous System after Traumatic Brain Injury

Nagamoto-Combs, Kumi, McNeal, David W., Morecraft, Robert J., Combs, Colin K.·2007·Journal of Neurotrauma

Abstract

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.

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Crossref · 10.1089/neu.2007.0377

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  • TBI is a biphasic injury: after the mechanical primary injury, a secondary dystrophic state produces long-term dysfunction including elevated neuroinflammation due to blood-brain barrier disruption, increased oxidative stress, and persistent changes in the microglial population.

    “TBI is a biphasic injury: after the mechanical primary injury, a secondary dystrophic state produces long-term dysfunction in the brain that includes elevated neuroinflammation as a result of blood-brain barrier disruption, increased oxidative stress, and persistent changes in the microglial population [100–106].”

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Authors
Nagamoto-Combs, K., McNeal, D. W., Morecraft, R. J., & Combs, C. K.
Affiliations
  • Department of Pharmacology, Physiology and Therapeutics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota.
  • University of South Dakota (US)
  • University of North Dakota (US)
Venue
Journal of Neurotrauma
Published
2007-11
Volume
24
Issue
11
Pages
1719-1742
ISSN
  • 0897-7151 (ISSN-L)
  • 1557-9042
OpenAlex
W2092803207
Cited by
156
References
67
Citations by year
2026: 2 · 2025: 10 · 2024: 7 · 2023: 2 · 2022: 5 · 2021: 10 · 2020: 11 · 2019: 8 · 2018: 4 · 2017: 12 · 2016: 7 · 2015: 11 · 2014: 20 · 2013: 16 · 2012: 12
FWCI
2.76
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Neurotrauma (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Neurological Disorders and Stroke (NS-046367)
Topics
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
Keywords
traumatic brain injury, microglial activation, microglia/macrophage activation, rhesus monkeys, premotor cortex, corticospinal tract, CD68, brain-derived neurotrophic factor, TrkB receptor, axonal degeneration, long-term recovery, neuroinflammation, cytokines, fine motor function
MeSH terms
CD68 Molecule, Animals, Brain Injuries, Cervical Vertebrae, Gliosis, Macaca mulatta, Macrophages, Male, Spinal Cord, Time Factors, Antigens, Differentiation, Myelomonocytic, Antigens, CD, Microglia, Brain-Derived Neurotrophic Factor, Receptor, trkB

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