A comparative histological analysis of two models of nerve root avulsion injury in the adult rat

D. J. Chew, T. Carlstedt and P. J Shortland (2011) Neuropathology and Applied Neurobiology 37, 613–632 A comparative histological analysis of two models of nerve root avulsion injury in the adult rat Aims: This study has investigated the reliability of the artificial surgical model dorsal root rhizotomy (DRR), to the surgical tearing of the roots, avulsion, that occurs clinically. Root avulsion of the limb nerves is common in high‐impact motor vehicle accidents and results in paraesthesia, paralysis and intractable pain. Limited treatment options are largely due to a lack of basic research on underlying mechanisms, and few animal models. We assess this limitation by histologically assessing the spatial and temporal injury profile of dorsal root avulsion (DRA) and DRR within the spinal cord. Methods: Rats underwent DRR, DRA or sham surgery to the L3–L6 dorsal roots unilaterally. At 1, 2, 14, and 28 days post injury, immunohistochemical density staining was used to characterize the progression of spinal cord trauma. Neuronal (NeuN) and vascular degeneration (RECA‐1), inflammatory infiltrate (ED1, anti‐neutrophil), gliosis (Iba1, GFAP) and apoptosis (TUNEL) were assessed. Results: Unilateral DRA produced a prolonged and bilateral glial and inflammatory response, and vascular degeneration compared to transient and unilateral effects after DRR. Transsynaptic neurodegeneration after DRA was greater than after DRR, and progressed across 28 days coinciding with gliosis and macrophage infiltration. Conclusions: Rhizotomy leads to a milder representation of the spinal cord trauma that occurs after ‘true’ avulsion injury. We recommend DRA be used in the future to more reliably model clinical avulsion injury. Avulsion is an injury with a chronic profile of degenerative and inflammatory progression, and this theoretically provides a window of clinical therapeutic opportunity in treatment of secondary trauma progression.