title: Atomic force microscopy reveals important differences in axonal resistance to injury.
abstract: Axonal degeneration after traumatic brain injury and nerve compression is considered a common underlying cause of temporary as well as permanent disability. Because a proper functioning of neural network requires phase coherence of all components, even subtle changes in circuitry may lead to network failure. However, it is still not possible to determine which axons will recover or degenerate after injury. Several groups have studied the pressure threshold for axonal injury within a nerve, but difficulty accessing the injured region; insufficient imaging methods and the extremely small dimensions involved have prevented the evaluation of the response of individual axons to injury. We combined microfluidics with atomic force microscopy and in vivo imaging to estimate the threshold force required to 1), uncouple axonal transport without impairing axonal survival, and 2), compromise axonal survival in both individual and bundled axons. We found that rat hippocampal axons completely recover axonal transport with no detectable axonal loss when compressed with pressures up to 65 ± 30 Pa for 10 min, while dorsal root ganglia axons can resist to pressures up to 540 ± 220 Pa. We investigated the reasons for the differential susceptibility of hippocampal and DRG axons to mechanical injury and estimated the elasticity of live axons. We found that dorsal root ganglia axons have a 20% lower elastic modulus than hippocampal axons. Our results emphasize the importance of the integrity of the axonal cytoskeleton in deciding the axonal fate after damage and open up new avenues to improve injury diagnosis and to identify ways to protect axons.
authors.affiliation: Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Program in NeuroEngineering, McGill University, Montreal, Quebec, Canada; Institute of Medical Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: margaret.magdesian@mcgill.ca.
authors.forename: Margaret H
authors.initials: MH
authors.lastname: Magdesian
authors.affiliation: Program in NeuroEngineering, McGill University, Montreal, Quebec, Canada; Department of Physics, McGill University, Montreal, Quebec, Canada.
authors.forename: Fernando S
authors.initials: FS
authors.lastname: Sanchez
authors.affiliation: Department of Physics, McGill University, Montreal, Quebec, Canada.
authors.forename: Monserratt
authors.initials: M
authors.lastname: Lopez
authors.affiliation: Program in NeuroEngineering, McGill University, Montreal, Quebec, Canada; Department of Physics, McGill University, Montreal, Quebec, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Thostrup
authors.affiliation: Department of Physics, McGill University, Montreal, Quebec, Canada.
authors.forename: Nela
authors.initials: N
authors.lastname: Durisic
authors.affiliation: Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Program in NeuroEngineering, McGill University, Montreal, Quebec, Canada.
authors.forename: Wiam
authors.initials: W
authors.lastname: Belkaid
authors.affiliation: Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Program in NeuroEngineering, McGill University, Montreal, Quebec, Canada.
authors.forename: Dalinda
authors.initials: D
authors.lastname: Liazoghli
authors.affiliation: Program in NeuroEngineering, McGill University, Montreal, Quebec, Canada; Department of Physics, McGill University, Montreal, Quebec, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Grütter
authors.affiliation: Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Program in NeuroEngineering, McGill University, Montreal, Quebec, Canada.
authors.forename: David R
authors.initials: DR
authors.lastname: Colman
mesh_terms: D000818:Animals; D001370:Axonal Transport; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D001696:Biomechanical Phenomena; D019245:Compressive Strength; D003250:Constriction; D004548:Elasticity; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D006624:Hippocampus / Q000166:cytology; D008297:Male; D055595:Mechanical Phenomena; D046210:Microfluidic Analytical Techniques; D018625:Microscopy, Atomic Force; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley