Major histocompatibility complex class II expression by activated microglia caudal to lesions of descending tracts in the human spinal cord is not associated with a T cell response

Abstract

Lesion-induced microglial/macrophage responses were investigated in post-mortem human spinal cord tissue of 20 patients who had died at a range of survival times after spinal trauma or brain infarction. Caudal to the spinal cord injury or brain infarction, a strong increase in the number of activated microglial cells was observed within the denervated intermediate grey matter and ventral horn of patients who died shortly after the insult (4-14 days). These cells were positive for the leucocyte common antigen (LCA) and for the major histocompatibility complex class II antigen (MHC II), with only a small proportion staining for the CD68 antigen. After longer survival times (1-4 months), MHC II-immunoreactivity (MHC II-IR) was clearly reduced in the grey matter but abundant in the white matter, specifically within the degenerating corticospinal tract, co-localising with CD68. In this fibre tract, elevated MHC II-IR and CD68-IR were still detectable 1 year after trauma or stroke. It is likely that the subsequent expression of CD68 on MHC II-positive microglia reflects the conversion to a macrophage phenotype, when cells are phagocytosing degenerating presynaptic terminals in grey matter target regions at early survival times and removing axonal and myelin debris in descending tracts at later survival times. No T or B cell invasion or involvement of co-stimulatory B7 molecules (CD80 and CD86) was observed. It is possible that the up-regulation of MHC II on microglia that lack the expression of B7 molecules may be responsible for the prevention of a T cell response, thus protecting the spinal cord from secondary tissue damage.

Secondary Neurodegeneration in Remote Regions After Focal Cerebral Infarction

“…Human leukocyte antigen -DA-positive microglia were detected in the gray matter of the spinal cord contralateral to the infarct within 2 weeks after stroke. 6,7 As survival time progressed from 5 weeks to 4 months, the numbers of human leukocyte antigen-DA-positive microglia decreased in the gray matter but were abundant within the contralateral corticospinal tract. Although the role of these activated microglia in Wallerian degeneration was unclear, they were believed to contribute to removal of the degenerating axons.…”

“…Although the role of these activated microglia in Wallerian degeneration was unclear, they were believed to contribute to removal of the degenerating axons. 6,7 Plain CT and Conventional MRI The neuroimaging features of secondary neurodegeneration have been summarized in the Table. The CT scan revealed atrophy of the thalamus and pyramidal tract at the chronic phase after massive cerebral infarction. Tamura et al 16 first reported progressive shrinkage of the ipsilateral thalamus after MCA infarction in 15 (45.5%) of the 33 patients.…”

“…For example, after cerebral infarction in the middle cerebral artery (MCA) territory, neuronal death, gliosis, and axonal degeneration have been found in the ipsilateral thalamus, substantia nigra (SN), and distal pyramidal tract, all of which lie outside the MCA territory. [2][3][4][5][6][7] This kind of secondary neurodegeneration occurs selectively in such areas several days or weeks after stroke onset, and this can be detected by neuroimaging techniques. 8 For quite a long time, the role of secondary degeneration in stroke recovery has not been well understood.…”

Subacute human spinal cord contusion: few lymphocytes and many macrophages

“…This observation is consistent with previous report in human SCI. 20 Recent studies have shown that injection of blood-derived macrophages activated exogenously may be beneficial in rodent models of SCI. [21][22][23][24] However, much remains to be learned about the mechanisms involved in this apparent beneficial effect.…”

Cell Cycle Activation Contributes to Increased Neuronal Activity in the Posterior Thalamic Nucleus and Associated Chronic Hyperesthesia after Rat Spinal Cord Contusion

“…After SCI, chronic activation of microglia and astrocytes are found at the lesion site, caudal dorsal horn, and thalamus [21,[25][26][27][28][29][30]. Such changes have been implicated in the induction and maintenance of SCI pain.…”