Table 2.
Kinetics of wound healing of the nerve: main phases and players
| Destruction | Repair | Remodeling | |
|---|---|---|---|
| Days following injury | |||
| When | 2 to 3 (prolonged up to 7-14) | 4 to weeks | 8 to weeks |
| Where | cell body | proximal axon segment | distal axon segment |
| injured axon terminal | |||
| distal axonal segment | |||
| What | chromatolysis | growth cone sprouting and elongation | nerve remodeling (supernumerary axonal sprout degeneration) reconnection with target (muscle re-innervation) |
| Wallerian degeneration (myelin clearance) | |||
| Who | cell body (1) | Schwann cells (4) (5) | pericytes (7) |
| B cells, macrophages (2) | axons (6) | Schwann cells (8) | |
| Schwann cells (3) | muscle fibers (9) (10) | ||
| How | hypertrophy, protein synthesis(1) | NGF (4) | CNTF (7) (8) |
| immune response (2) | BDNF (5) | IGF-1(9) | |
| MCP-1, LIF (3) | NT-3 and−4/5 (6) | FGF(10) | |
Following injury, regeneration of the nerve can be schematically divided in three main phases. Complete nerve regeneration in humans depends to a large extent on the length of the gap to be filled and may take many weeks. In addition to the timeline (When), each row indicates the tissue involved (Where), the main output (What), the cell type involved most (Who) and some of the main molecular mediators (How) responsible for the various phases of wound healing. Brain-derived neurotrophic factor (BDNF); ciliary neurotrophic factor (CNTF); fibroblast growth factor (FGF); insulin-like growth factor-1 (IGF-1); leukemia inhibitory factor (LIF); monocyte chemoattractant protein-1 (MCP-1); nerve growth factor (NGF); neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5). Matching superscripts highlight the cells that produce the corresponding growth factors.