American Society for Peripheral Nerve

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Monocyte Chemotactic Protein-1 Expression in Rats Decreases with Age in Response to Peripheral Nerve Injury
Zhongyu Li, MD, PhD; Johannes F. Plate, MD; Jiaozhong Cai; Jonathan C. Barnwell, MD; Thomas L. Smith, PhD
Department of Orthpaedic Surgery, Wake Forest School of Medicine, Winston-Salem, NC, USA

Hypothesis: Monocyte chemotactic protein-1 (MCP-1) is released from Schwann cells in response to peripheral nerve injury attracting and activating macrophages to clear myelin debris. Increasing age leads to lower rates of nerve recovery. This study hypothesized that expression of MCP-1 in response to nerve injury decreases with age resulting in decreased macrophage recruitment and activation, and therefore prolonged myelin phagocytosis during Wallerian degeneration limiting axonal regrowth.

Methods: In 15 young (mean weight 146g) and 15 old (mean weight 471g) Lewis rats, unilateral sciatic nerve crush injury was induced. Both sciatic nerves from five animals in each group were harvested at one, three, and ten days after injury. RNA was extracted using TRI reagent (Ambion), and assessed for quantity and purity (NanoDrop Technologies), and viability (electrophoresis). The RNA was transcribed to cDNA using random hexamers and Superscript II (Invitrogen). Real-time polymerase chain reaction (rt-PCR) was performed using Taqman (Applied Biosystems) for MCP-1 as target gene and Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as endogenous control. Histological analysis of axon diameter, the number of axon, and mean nerve fascicle area was performed.

Results: In young animals, MCP-1 expression increased 7.7 fold one day after injury relative to the contralateral control and remained similarly elevated at three days (8.1 fold) and ten days (4.9 fold) after injury (p>0.05). In old animals, MCP-1 expression increased 10.6 fold on day one, but was significantly reduced three (0.3 fold) and ten days (1.3 fold) following injury (p<0.05). Two-way ANOVA revealed no significant main effect of age on the overall MCP-1 expression. Histological analysis revealed differences in axon diameter, and nerve fascicle area relative to total cross-sectional area between age groups at different time points. The total number of axons was similar in both groups at each time point (p>0.05).

Summary: The significant reduction of MCP-1 expression in old animals revealed that aging affects the ability for a sustained upregulation of the MCP-1 gene in response to injury. Thus, macrophage recruitment and activation may be decreased compared to young animals, limiting the rate of myelin clearance during Wallerian degeneration.


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