Traumatic neuroma in continuity injury model in rodents.
Traumatic neuroma in continuity (NIC) results in profound neurological deficits, and its management poses the most challenging problem to peripheral nerve surgeons today. The absence of a clinically relevant experimental model continues to handicap our ability to investigate ways of better diagnosis and treatment for these disabling injuries. Various injury techniques were tested on Lewis rat sciatic nerves. Optimal experimental injuries that consistently resulted in NIC combined both intense focal compression and traction forces. Nerves were harvested at 0, 5, 13, 21, and 65 days for histological examination. Skilled locomotion and ground reaction force (GRF) analysis were performed up to 9 weeks on the experimental (n=6) and crush-control injuries (n=5). Focal widening, disruption of endoneurium and perineurium with aberrant intra- and extrafascicular axonal regeneration and progressive fibrosis was consistently demonstrated in 14 of 14 nerves with refined experimental injuries. At 8 weeks, experimental animals displayed a significantly greater slip ratio in both skilled locomotor assessments, compared to nerve crush animals (p<0.01). GRFs of the crush- injured animals showed earlier improvement compared to the experimental animals, whose overall GRF patterns failed to recover as well as the crush group. We have demonstrated histological features and poor functional recovery consistent with NIC formation in a rat model. The injury mechanism employed combines traction and compression forces akin to the physical forces at play in clinical nerve injuries. This model may serve as a tool to help diagnose this injury earlier and to develop intervention strategies to improve patient outcomes.
Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
Jacob Daniel de Villiers
JD
Alant
Stephen William Peter
SW
Kemp
Kathleen Joy Ong Lopez
KJ
Khu
Ranjan
R
Kumar
Aubrey A
AA
Webb
Rajiv
R
Midha
D000818:Animals; D008297:Male; D023421:Models, Animal; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000502:physiology*; D009463:Neuroma / Q000473:pathology* / Q000503:physiopathology; D010524:Peripheral Nervous System Neoplasms / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function / Q000502:physiology*; D012584:Sciatic Nerve / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology