Quinolinic acid accumulation in injured spinal cord: time course, distribution, and species differences between rat and guinea pig.
Experimental compression injury of the spinal cord in guinea pigs results in delayed neurologic deficits that continue to increase in severity for several days following trauma, coincident with inflammatory responses, including invasion of the lesion by mononuclear phagocytes and increased levels of the neurotoxin quinolinic acid (QUIN). Inflammatory responses and QUIN elevation also occur following spinal cord contusion in rats, but maximal neurologic deficits develop immediately. In this study, somatosensory evoked potentials (SEP) and tissue, serum, and cerebrospinal fluid levels of QUIN were measured in guinea pigs and rats following similar compression injuries of the thoracic spinal cord. SEP changes differed between the species, consistent with other neurological changes. In guinea pigs, increases in QUIN levels at the lesion site began at 1 day postinjury, achieved maximal elevation (100-fold) by 12 days, then declined, but remained above serum levels at 25 days postinjury. A similar increase occurred in adjacent areas of the spinal cord, with lower peak levels. In rats, tissue QUIN at the center of the lesion remained below serum levels at all times, increasing moderately (<10-fold) up to 7 days, then decreasing between 7 and 25 days. These data demonstrate differences in the time course and magnitude of QUIN accumulation and neurological deficit between guinea pig and rat, which may relate to differences in secondary pathological mechanisms. Such profound differences may affect the use of these species for evaluation of experimental therapy in this and other inflammatory conditions of the central nervous system.
Blight
A R
AR
Division of Neurosurgery, University of North Carolina at Chapel Hill, 27599, USA.
Leroy
E C
EC
Heyes
M P
MP
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D017378:Quinolinic Acid / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution
D017378:Quinolinic Acid