Deconstructing locomotor networks with experimental injury to define their membership.
Although spinal injury is a major cause of chronic disability, the mechanisms responsible for the lesion pathophysiology and their dynamic evolution remain poorly understood. Hence, current treatments aimed at blocking damage extension are unsatisfactory. To unravel the acute spinal injury processes, we have developed a model of the neonatal rat spinal cord in vitro subjected to kainate-evoked excitotoxicity or metabolic perturbation (hypoxia, aglycemia, and free oxygen radicals) or their combination. The study outcome is fictive locomotion one day after the lesion and its relation to histological damage. Excitotoxicity always suppresses locomotor network activity and produces large gray matter damage, while network bursting persists supported by average survival of nearly half premotoneurons and motoneurons. Conversely, metabolic perturbation simply depresses locomotor network activity as damage mainly concerns white rather than gray matter. Coapplication of kainate and metabolic perturbation completely eliminates locomotor network activity. These results indicate distinct cellular targets for excitotoxic versus dysmetabolic damage with differential consequences on locomotor pattern formation. Furthermore, these data enable to estimate the minimal network membership compatible with expression of locomotor activity.
International School for Advanced Studies, Trieste, Italy. nistri@sissa.it
Andrea
A
Nistri
Giuliano
G
Taccola
Miranda
M
Mladinic
Gayane
G
Margaryan
Anujaianthi
A
Kuzhandaivel
D000818:Animals; D000831:Animals, Newborn; D002908:Chronic Disease; D003292:Convulsants / Q000633:toxicity; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005971:Glutamates / Q000378:metabolism; D007395:Interneurons / Q000502:physiology; D007608:Kainic Acid / Q000633:toxicity; D008124:Locomotion / Q000502:physiology*; D008159:Lumbar Vertebrae / Q000293:injuries / Q000473:pathology; D009415:Nerve Net / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology; D009474:Neurons / Q000502:physiology; D009498:Neurotoxins / Q000633:toxicity; D051381:Rats; D013119:Spinal Cord Injuries / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D013331:Strychnine / Q000633:toxicity; D014947:Wounds and Injuries / Q000378:metabolism / Q000503:physiopathology
D003292:Convulsants; D018690:Excitatory Amino Acid Agonists; D005971:Glutamates; D009498:Neurotoxins; D013331:Strychnine; D007608:Kainic Acid