title: Motorneuron protection by N-acetyl-cysteine after ventral root avulsion and ventral rhizotomy.
abstract: Motor recovery after proximal nerve injury remains extremely poor, despite advances in surgical care. Several neurobiological hurdles are implicated, the most fundamental being extensive cell death within the motorneuron pool. N-acetyl-cysteine almost completely protects sensory neurons after peripheral axotomy, hence its efficacy in protecting motorneurons after ventral root avulsion/rhizotomy was investigated. In adult rats, the motorneurons supplying medial gastrocnemius were unilaterally pre-labelled with retrograde tracer (true-blue/fluoro-gold), prior to L5 and 6 ventral root avulsion, or rhizotomy. Groups received either intraperitoneal N-acetyl-cysteine (ip, 150 or 750 mg/kg/day), immediate or delayed intrathecal N-acetyl-cysteine treatment (it, 2.4 mg/day), or saline; untreated animals served as controls. Either 4 (avulsion model) or 8 (rhizotomy model) weeks later, the pre-labelled motorneurons' mean soma area and survival were quantified. Untreated controls possessed markedly fewer motorneurons than normal due to cell death (avulsion 53% death; rhizotomy 26% death, P<0.01 vs. normal). Motorneurons were significantly protected by N-acetyl-cysteine after avulsion (ip 150 mg/kg/day 40% death; it 30% death, P<0.01 vs. no treatment), but particularly after rhizotomy (ip 150 mg/kg/day 17% death; ip 750 mg/kg/day 7% death; it 5% death, P<0.05 vs. no treatment). Delaying intrathecal treatment for 1 week after avulsion did not impair neuroprotection, but a 2-week delay was deleterious (42% death, P<0.05 vs. 1-week delay, 32% death). Treatment prevented the decrease in soma area usually found after both types of injury. N-acetyl-cysteine has considerable clinical potential for adjuvant treatment of major proximal nerve injuries, including brachial plexus injury, in order that motorneurons may survive until surgical repair facilitates regeneration.
authors.affiliation: Department of Surgical and Perioperative Science, Section for Hand and Plastic Surgery, University Hospital, Umeå, Sweden.
authors.forename: C-G
authors.initials: CG
authors.lastname: Zhang
authors.forename: D
authors.initials: D
authors.lastname: Welin
authors.forename: L
authors.initials: L
authors.lastname: Novikov
authors.forename: J-O
authors.initials: JO
authors.lastname: Kellerth
authors.forename: M
authors.initials: M
authors.lastname: Wiberg
authors.forename: A M
authors.initials: AM
authors.lastname: Hart
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D016923:Cell Death / Q000502:physiology; D005260:Female; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019051:Rhizotomy / Q000379:methods*; D012584:Sciatic Nerve / Q000293:injuries* / Q000601:surgery; D013126:Spinal Nerve Roots / Q000293:injuries* / Q000601:surgery
chemical_list: D018696:Neuroprotective Agents; D000111:Acetylcysteine