title: Acute glial activation by stab injuries does not lead to overt damage or motor neuron degeneration in the G93A mutant SOD1 rat model of amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease where motor neurons within the brain and spinal cord are lost, leading to paralysis and death. Recently, a correlation between head trauma and the incidence of ALS has been reported. Furthermore, new invasive neurosurgical studies are being planned which involve inserting needles directly to the spinal cord. We therefore tested whether acute trauma to the spinal cord via a knife wound injury would lead to accelerated disease progression in rodent models of ALS (SOD1(G93A) rats). A longitudinal stab injury using a small knife was performed within the lumbar spinal cord region of presymptomatic SOD1(G93A) rats. Host glial activation was detected in the lumbar area surrounding a micro-knife lesion at 2 weeks after surgery in both wild type and SOD1(G93A) animals. However, there was no sign of motor neuron loss in the injured spinal cord of any animal and normal motor function was maintained in the ipsilateral limb. These results indicate that motor neurons in presymptomatic G93A animals are not affected by an invasive puncture wound injury involving reactive astrocytes. Furthermore, acute trauma alone does not accelerate disease onset or progression in this ALS model which is important for future strategies of gene and cell therapies directly targeting the spinal cord of ALS patients.
authors.affiliation: The Waisman Center, University of Wisconsin-Madison, Madison, WI, USA. msuzuki@svm.vetmed.wisc.edu
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Suzuki
authors.forename: Sandra
authors.initials: S
authors.lastname: Klein
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Wetzel
authors.forename: Michael
authors.initials: M
authors.lastname: Meyer
authors.forename: Jacalyn
authors.initials: J
authors.lastname: McHugh
authors.forename: Craig
authors.initials: C
authors.lastname: Tork
authors.forename: Antonio
authors.initials: A
authors.lastname: Hayes
authors.forename: Clive N
authors.initials: CN
authors.lastname: Svendsen
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000473:pathology*; D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D039481:CD11b Antigen / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D007839:Functional Laterality; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D009046:Motor Neurons / Q000473:pathology*; D009410:Nerve Degeneration / Q000209:etiology* / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D013119:Spinal Cord Injuries / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D025801:Ubiquitin; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D002795:Choline O-Acetyltransferase