Reinnervation of hind limb extremity after lumbar dorsal root ganglion injury.
Loss of dorsal root ganglion neuron, or injury to dorsal roots, induces permanent somatosensory defect without therapeutic option. We explored an approach to restoring hind limb somatosensory innervation after elimination of L4, L5 and L6 dorsal root ganglion neurons in rats. Somatosensory pathways were reconstructed by connecting L4, L5 and L6 lumbar dorsal roots to T10, T11 and T12 intercostal nerves, respectively, thus allowing elongation of thoracic ganglion neuron peripheral axons into the sciatic nerve. Connection of thoracic dorsal root ganglion neurons to peripheral tissues was documented 4 and 7 months after injury. Myelinated and unmyelinated fibers regrew in the sciatic nerve. Nerve terminations expressing calcitonin-gene-related-peptide colonized the footpad skin. Retrograde tracing showed that T10, T11 and T12 dorsal root ganglion neurons expressing calcitonin-gene-related-peptide or the neurofilament RT97 projected axons to the sciatic nerve and the footpad skin. Recording of somatosensory evoked potentials in the upper spinal cord indicated connection between the sciatic nerve and the central nervous system. Hind limb retraction in response to nociceptive stimulation of the reinnervated footpads and reversion of skin lesions suggested partial recovery of sensory function. Proprioceptive defects persisted. Delayed somatosensory reinnervation of the hind limb after destruction of lumbar dorsal root neurons in rats indicates potential approaches to reduce chronic disability after severe injury to somatosensory pathways.
Liu
Song
S
Unité Rétrovirus et Transfert Génétique, INSERM U622, Department of Neuroscience, Institut Pasteur, 75015 Paris, France.
Bréjot
Thomas
T
Cressant
Arnaud
A
Bacci
Josette
J
Saïd
Gérard
G
Tadié
Marc
M
Heard
Jean Michel
JM
D000578:Amidines / Q000378:metabolism; D000818:Animals; D001572:Benzofurans / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods; D004576:Electromyography / Q000379:methods; D005073:Evoked Potentials, Somatosensory / Q000502:physiology / Q000528:radiation effects; D005727:Ganglia, Spinal / Q000293:injuries* / Q000473:pathology* / Q000648:ultrastructure; D007150:Immunohistochemistry / Q000379:methods; D037102:Lectins / Q000378:metabolism; D035002:Lower Extremity / Q000294:innervation* / Q000503:physiopathology; D008297:Male; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D009416:Nerve Regeneration; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D010147:Pain Measurement / Q000379:methods; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011597:Psychomotor Performance / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019051:Rhizotomy / Q000379:methods; D013997:Time Factors
D000578:Amidines; D001572:Benzofurans; D037102:Lectins; D016900:Neurofilament Proteins; C038675:true blue; C037945:diamidino yellow; D010751:Phosphopyruvate Hydratase; D015740:Calcitonin Gene-Related Peptide