The Time Course of MHC-I Expression in C57BL/6J and A/J Mice Correlates with the Degree of Retrograde Gliosis in the Spinal Cord following Sciatic Nerve Crush

Abstract

The pleiotropic role of the major histocompatibility complex class I (MHC-I) reflects the close association between the nervous and immune systems. In turn, MHC-I upregulation postinjury is associated with a better regenerative outcome in isogenic mice following peripheral nerve damage. In the present work, we compared the time course of neuronal, glial, and sensorimotor recovery (1, 3, 5, 7, and 28 days after lesion—dal) following unilateral sciatic nerve crush in A/J and C57BL/6J mice. The A/J strain showed higher expression of MHC-I (7 dal, ** p < 0.01), Iba-1 (microglial reaction, 7 dal, *** p < 0.001), and GFAP (astrogliosis, 5 dal, * p < 0.05) than the C57BL/6J counterpart. Synaptic coverage (synaptophysin) was equivalent in both strains over time. In addition, mRNA expression of microdissected spinal motoneurons revealed an increase in cytoskeleton-associated molecules (cofilin, shp2, and crmp2, * p < 0.05), but not trkB, in C57BL/6J mice. Gait recovery, studied by the sciatic functional index, was faster in the A/J strain, despite the equivalent results of C57BL/6J at 28 days after injury. A similar recovery was also seen for the nociceptive threshold (von Frey test). Interestingly, when evaluating proprioceptive recovery, C57BL/6J animals showed an enlarged base of support, indicating abnormal ambulation postinjury. Overall, the present results reinforce the role of MHC-I expression in the plasticity of the nervous system following axotomy, which in turn correlates with the variable recovery capacity among strains of mice.

Embryonic stem cells overexpressing high molecular weight FGF2 isoform enhance recovery of pre-ganglionic spinal root lesion in combination with fibrin biopolymer mediated root repair

“…Based on the overall positive morphological and behavioral outcome, it is possible that such activation contributed to the regenerative response by accelerating debris phagocytosis. Microglial cells can acquire a pro-regenerative profile that is beneficial to tissue repair [65][66][67]. Nevertheless, the qRT-PCR, two weeks after the injury, did not provide evidence of growth factors or pro-inflammatory cytokines upregulation, although it might have happened at earlier time points.…”

Effects of local and systemic treatment with human natural killer-1 mimetic peptide (HNK-1) after ventral root avulsion and reimplantation in mice

“…This finding suggests that, in the experimental model in mice, the overall glial reaction is more intense and tends to become chronic, which can partially explain the comparatively reduced performance of reimplantation in neuroprotection. Indeed, the pathology of spinal cord injury in rats and mice is known to be distinct [ 72 ], and differences in inflammatory responses have been observed even between mouse strains [ 73 , 74 ].…”

Dissecting Genetic Mechanisms of Differential Locomotion, Depression, and Allodynia after Spinal Cord Injury in Three Mouse Strains

“…Mice of the A/J and BALB/c strains are albino with different brain anatomic structure [39][40][41][42]. Following unilateral sciatic nerve crush, the A/J strain showed elevated expression of major histocompatibility complex class I and increased microglial reaction and astrogliosis compared to those in C57BL/6 animals [43]. BALB/c mice were significantly more susceptible to tissue damage resulting from permanent focal cerebral ischemia than C57BL/6 mice [44].…”