{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:11:41Z","timestamp":1790770301502,"version":"4.1.0"},"reference-count":48,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JNS"],"published-print":{"date-parts":[[2010,4]]},"abstract":"<jats:sec>\n<jats:title>Object<\/jats:title>\n<jats:p>Surgical repair of peripheral nerves following chronic nerve injury is associated with poor axonal regeneration and outcome. An underlying possibility is that chronic injuries may increase motoneuron cell death. The hypothesis that substantial motoneuron death follows chronic and sequential nerve injuries was tested in adult rats in this study.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Thirty adult male Lewis rats underwent bilateral multistage surgeries. At initial surgery, Fast Blue (FB) tracer was injected at a nerve-crush injury site in the right control femoral motor nerve. The left femoral motor nerve was transected at the same level and either capped to prevent regeneration (Group 1), or repaired to allow axonal regeneration and reinnervation of the target quadriceps muscle (Group 2) (15 rats in each group). After 8 weeks in 6 rats\/group, the left femoral nerve was cut and exposed to FB just proximal to prior nerve capping or repair and the rats were evaluated for FB-labeled motoneuron counts bilaterally in the spinal cord (this was considered survival after initial injury). In the remaining 9 animals\/group, the left nerve was recut (sequential injury), exposed to FB, and repaired to a fresh distal saphenous nerve stump to permit axonal regeneration. Following another 6 weeks, Fluoro-Gold, a second retrograde tracer, was applied to the cut distal saphenous nerve. This allowed us to evaluate the number of motoneurons that survived (maintained FB labeling) and the number of motoneurons that survived but that also regenerated axons (double labeled with FB and Fluoro-Gold).<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>A mean number of 350 and 392 FB-labeled motoneurons were found after 8 weeks of nerve injury on the right and the left sides, respectively. This indicated no significant cell death due to initial nerve injury alone. A similar number (mean 390) of motoneurons were counted at final end point at 14 weeks, indicating no significant cell death after sequential and chronic nerve injury. However, only 50% (mean 180) of the surviving motoneurons were double labeled, indicating that only half of the population regenerated their axons.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The hypothesis that significant motoneuron cell death occurs after chronic and or sequential nerve injury was rejected. Despite cell survival, only 50% of motoneurons are capable of exhibiting a regenerative response, consistent with our previous findings of reduced regeneration after chronic axotomy.<\/jats:p><\/jats:sec>","DOI":"10.3171\/2009.8.jns09812","type":"journal-article","created":{"date-parts":[[2009,9,18]],"date-time":"2009-09-18T14:54:05Z","timestamp":1253285645000},"page":"890-899","source":"Crossref","is-referenced-by-count":26,"title":["Motoneuron survival after chronic and sequential peripheral nerve injuries in the rat"],"prefix":"10.3171","volume":"112","author":[{"given":"Qing-Gui","family":"Xu","sequence":"first","affiliation":[{"name":"Division of Neurosurgery, Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Forden","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah K.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessa","family":"Gordon","sequence":"additional","affiliation":[{"name":"Center for Neuroscience, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Midha","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1-1120890","series-title":"Anat Rec","first-page":"239","article-title":"Estimation of nuclear population from microtome sections","volume":"94","author":"Abercrombie","year":"1946"},{"key":"b2-1120890","series-title":"J Neurosci","first-page":"2602","article-title":"Brief electrical stimulation promotes the speed and accuracy of motor axonal regeneration","volume":"20","author":"Al Majed","year":"2000"},{"key":"b3-1120890","series-title":"Neurol Res","first-page":"211","article-title":"The influence of GDNF on the timecourse and extent of motoneuron loss in the cervical spinal cord after brachial plexus injury in the neonate","volume":"26","author":"Aszmann","year":"2004"},{"key":"b4-1120890","series-title":"Exp Neurol","first-page":"610","article-title":"Glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor sustain the axonal regeneration of chronically axotomized motoneurons in vivo","volume":"183","author":"Boyd","year":"2003"},{"key":"b5-1120890","series-title":"J Neurosci","first-page":"1026","article-title":"Preferential reinnervation of motor nerves by regenerating motor axons","volume":"8","author":"Brushart","year":"1988"},{"key":"b6-1120890","series-title":"Operative Nerve Repair and Reconstruction","first-page":"215","article-title":"The mechanical and humoral control of specificity in nerve repair","author":"Brushart","year":"1991"},{"key":"b7-1120890","series-title":"Biosystems","first-page":"243","article-title":"Is it possible to predict the outcome of peripheral nerve injuries? A probability model based on prosoects for regenerating neurites","volume":"20","author":"De Medinaceli","year":"1987"},{"key":"b8-1120890","series-title":"Glia","first-page":"555","article-title":"Repeated injuries dramatically affect cells of the oligodendrocyte lineage: effects of PDGF and NT-3 in vitro","volume":"49","author":"Fressinaud","year":"2005"},{"key":"b9-1120890","series-title":"J Neurosci","first-page":"3876","article-title":"Contributing factors to poor functional recovery after delayed nerve repair: prolonged axotomy","volume":"15","author":"Fu","year":"1995"},{"key":"b10-1120890","series-title":"J Neurosci","first-page":"3886","article-title":"Contributing factors to poor functional recovery after delayed nerve repair: prolonged denervation","volume":"15","author":"Fu","year":"1995"},{"key":"b11-1120890","series-title":"Mol Neurobiol","first-page":"67","article-title":"The cellular and molecular basis of peripheral nerve regeneration","volume":"14","author":"Fu","year":"1997"},{"key":"b12-1120890","series-title":"Neurosurgery","first-page":"723","article-title":"Prolonged target deprivation reduces the capacity of injured motoneurons to regenerate","volume":"60","author":"Furey","year":"2007"},{"issue":"2","key":"b13-1120890","series-title":"Neurosurg Focus","first-page":"E3","article-title":"The role of neurotrophic factors in nerve regeneration","volume":"26","author":"Gordon","year":"2009"},{"key":"b14-1120890","series-title":"Acta Neurochir Suppl","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-3-211-72958-8_1","article-title":"The potential of electrical stimulation to promote functional recovery after peripheral nerve injury\u2013comparisons between rats and humans","volume":"100","author":"Gordon","year":"2007"},{"key":"b15-1120890","series-title":"J Peripher Nerv Syst","first-page":"236","article-title":"Experimental strategies to promote functional recovery after peripheral nerve injuries","volume":"8","author":"Gordon","year":"2003"},{"key":"b16-1120890","series-title":"Dev Neurosci","first-page":"255","article-title":"The effects of remaining axons on motoneuron survival and NOS expression following axotomy in the adult rat","volume":"19","author":"Gu","year":"1997"},{"key":"b17-1120890","series-title":"Neurochem Int","first-page":"417","article-title":"Gene expression and apoptosis in the spinal cord neurons after sciatic nerve injury","volume":"30","author":"Gu","year":"1997"},{"key":"b18-1120890","series-title":"J Neurosci Methods","first-page":"123","article-title":"Double-labeling of saphenous nerve neuron pools: a model for determining the accuracy of axon regeneration at the single neuron level","volume":"39","author":"Harsh","year":"1991"},{"key":"b19-1120890","series-title":"Neurol Res","first-page":"999","article-title":"Neuronal death after peripheral nerve injury and experimental strategies for neuroprotection","volume":"30","author":"Hart","year":"2008"},{"key":"b20-1120890","series-title":"J Reconstr Microsurg","first-page":"381","article-title":"Retrograde labeling in peripheral nerve research: it is not all black and white","volume":"23","author":"Hayashi","year":"2007"},{"key":"b21-1120890","series-title":"Arch Neurol","first-page":"1681","article-title":"Neuroprotection in the peripheral nervous system: rationale for more effective therapies","volume":"63","author":"Hoke","year":"2006"},{"key":"b22-1120890","series-title":"J Plast Reconstr Aesthet Surg","first-page":"472","article-title":"The influence of presurgical delay on functional outcome after reconstruction of brachial plexus injuries","volume":"62","author":"Jivan","year":"2009"},{"key":"b23-1120890","series-title":"Exp Brain Res","first-page":"245","article-title":"The effects of delayed nerve repair on neuronal survival and axonal regeneration after seventh cervical spinal nerve axotomy in adult rats","volume":"170","author":"Jivan","year":"2006"},{"key":"b24-1120890","series-title":"Neurol Res","first-page":"1030","article-title":"Growth factor and stem cell enhanced conduits in peripheral nerve regeneration and repair","volume":"30","author":"Kemp","year":"2008"},{"key":"b25-1120890","series-title":"Nerve Injuries: Operative Results from Major Nerve Injuries, Entrapments, and Tumors","author":"Kline","year":"1995"},{"key":"b26-1120890","series-title":"Exp Neurol","first-page":"77","article-title":"Time course and age dependence of motor neuron death following facial nerve crush injury: role of fibroblast growth factor","volume":"157","author":"Kuzis","year":"1999"},{"key":"b27-1120890","series-title":"Neuroscience","first-page":"337","article-title":"The role of apoptosis and excitotoxicity in the death of spinal motoneurons and interneurons after neonatal nerve injury","volume":"87","author":"Lawson","year":"1998"},{"key":"b28-1120890","series-title":"Scand J Plast Reconstr Surg Hand Surg","first-page":"1","article-title":"Early nerve repair after injury to the postganglionic plexus: an experimental study of sensory and motor neuronal survival in adult rats","volume":"37","author":"Ma","year":"2003"},{"key":"b29-1120890","series-title":"Exp Brain Res","first-page":"216","article-title":"Delayed loss of spinal motoneurons after peripheral nerve injury in adult rats: a quantitative morphological study","volume":"139","author":"Ma","year":"2001"},{"key":"b30-1120890","series-title":"Muscle Nerve","first-page":"1116","article-title":"Changes in nerve fiber numbers distal to a nerve repair in the rat sciatic nerve model","volume":"14","author":"Mackinnon","year":"1991"},{"key":"b31-1120890","series-title":"J Neurosci","first-page":"5698","article-title":"Reinnervation accuracy of the rat femoral nerve by motor and sensory neurons","volume":"16","author":"Madison","year":"1996"},{"key":"b32-1120890","series-title":"J Neurobiol","first-page":"185","article-title":"Motor neuron degeneration after sciatic nerve avulsion in adult rat evolves with oxidative stress and is apoptosis","volume":"40","author":"Martin","year":"1999"},{"key":"b33-1120890","series-title":"J Neurobiol","first-page":"181","article-title":"Injury-induced spinal motor neuron apoptosis is preceded by DNA single-strand breaks and is p53- and Bax-dependent","volume":"50","author":"Martin","year":"2002"},{"key":"b34-1120890","series-title":"Neurol Med Chir (Tokyo)","first-page":"187","article-title":"Peripheral nerve repair and grafting techniques: a review","volume":"40","author":"Matsuyama","year":"2000"},{"key":"b35-1120890","series-title":"Time course of cell death and elimination Exp Brain Res","first-page":"308","article-title":"Primary sensory neurons and satellite cells after peripheral axotomy in the adult rat","volume":"142","author":"McKay Hart","year":"2002"},{"key":"b36-1120890","series-title":"Management of Peripheral Nerve Problems","first-page":"319","article-title":"Evaluation of the neuroma in continuity","author":"Midha","year":"1998"},{"key":"b37-1120890","series-title":"Neurosurgery","first-page":"1289","article-title":"Regeneration into protected and chronically denervated peripheral nerve stumps","volume":"57","author":"Midha","year":"2005"},{"key":"b38-1120890","series-title":"J Neurosci Methods","first-page":"11","article-title":"Retrograde tracing with Fluoro-Gold: different methods of tracer detection at the ultrastructural level and neurodegenerative changes of backfilled neurons in long-term studies","volume":"103","author":"Naumann","year":"2000"},{"key":"b39-1120890","series-title":"J Trauma","first-page":"116","article-title":"Analysis of upper and lower extremity peripheral nerve injuries in a population of patients with multiple injuries","volume":"45","author":"Noble","year":"1998"},{"key":"b40-1120890","series-title":"J Neurosci Methods","first-page":"9","article-title":"Persistent neuronal labeling by retrograde fluorescent tracers: a comparison between Fast Blue, Fluoro-Gold and various dextran conjugates","volume":"74","author":"Novikova","year":"1997"},{"key":"b41-1120890","series-title":"Neuroreport","first-page":"2837","article-title":"Neonatal sciatic nerve transection induces TUNEL labeling of neurons in the rat spinal cord and DRG","volume":"8","author":"Oliveira","year":"1997"},{"key":"b42-1120890","series-title":"J Comp Neurol","first-page":"381","article-title":"Apoptosis of spinal interneurons induced by sciatic nerve axotomy in the neonatal rat is counteracted by nerve growth factor and ciliary neurotrophic factor","volume":"447","author":"Oliveira","year":"2002"},{"key":"b43-1120890","series-title":"J Neurosurg","first-page":"307","article-title":"Brachial plexus injury: factors affecting functional outcome in spinal accessory nerve transfer for the restoration of elbow flexion","volume":"98","author":"Samii","year":"2003"},{"key":"b44-1120890","series-title":"J Neurosurg","first-page":"881","article-title":"Surgical reconstruction of the musculocutaneous nerve in traumatic brachial plexus injuries","volume":"87","author":"Samii","year":"1997"},{"key":"b45-1120890","series-title":"Surgical Disorders of the Peripheral Nerves","author":"Seddon","year":"1972"},{"key":"b46-1120890","series-title":"Exp Neurol","first-page":"342","article-title":"Chronic Schwann cell denervation and the presence of a sensory nerve reduce motor axonal regeneration","volume":"176","author":"Sulaiman","year":"2002"},{"key":"b47-1120890","series-title":"Nerve and Nerve Injuries","author":"Sunderland","year":"1978"},{"key":"b48-1120890","series-title":"Nerve Injuries and their Repair. A Critical Appraisal","author":"Sunderland","year":"1991"}],"container-title":["Journal of Neurosurgery"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/112\/4\/article-p890.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/112\/4\/article-p890.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/112\/4\/article-p890.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T07:41:33Z","timestamp":1679902893000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/112\/4\/article-p890.xml"}},"subtitle":["Laboratory investigation"],"short-title":[],"issued":{"date-parts":[[2010,4]]},"references-count":48,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.3171\/2009.8.jns09812","relation":{},"ISSN":["0022-3085","1933-0693"],"issn-type":[{"value":"0022-3085","type":"print"},{"value":"1933-0693","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,4]]}}}