A new antioxidant compound H-290/51 modulates glutamate and GABA immunoreactivity in the rat spinal cord following trauma.
The involvement of the excitatory amino acid glutamate and the inhibitory amino acid gamma-amino butyric acid (GABA) in the pathophysiology of spinal cord injury is not known in details. This investigation is focused on the role of glutamate and GABA in a rat model of spinal cord trauma using immunohistochemistry. Spinal cord injury produced by a longitudinal incision of the right dorsal horn of the T10-11 segments resulted in profound edema and cell damage in the adjacent T9 segment at 5 h. Pretreatment with H-290/51 (50 mg/kg, p.o.), a potent antioxidant compound, effectively reduced the blood-spinal cord barrier (BSCB) permeability, edema formation and cell injury following trauma. At this time, untreated traumatised rats exhibited a marked increase in glutamate immunoreactivity along with a distinct decrease in GABA immunostaining in the T9 segment. These changes in glutamate and GABA immunoreactivity in traumatised rats were considerably attenuated by pretreatment with H-290/51. These results suggest that (i). oxidative stress contributes to alterations in glutamate and GABA in spinal cord injury, (ii). glutamate and GABA are important factors in the breakdown of the BSCB, edema formation and cell changes, and (iii). the antioxidant compound H-290/51 has a potential therapeutic value in the treatment of spinal cord injuries.
Sharma
H S
HS
Department of Medical Cell Biology, Biomedical Centre, Uppsala University, Uppsala, Sweden. Sharma@medcellbiol.uu.se
Sjöquist
P-O
PO
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000502:physiology; D004487:Edema / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D018696:Neuroprotective Agents / Q000378:metabolism; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000975:Antioxidants; D018696:Neuroprotective Agents; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid