Inhibition of x-irradiation-enhanced locomotor recovery after spinal cord injury by hyperbaric oxygen or the antioxidant nitroxide tempol.
OBJECTIVE
Hyperbaric oxygen (HBO), the nitroxide antioxidant tempol, and x-irradiation have been used to promote locomotor recovery in experimental models of spinal cord injury. The authors used x-irradiation of the injury site together with either HBO or tempol to determine whether combined therapy offers greater benefit to rats.


METHODS
Contusion injury was produced with a weight-drop device in rats at the T-10 level, and recovery was determined using the 21-point Basso-Beattie-Bresnahan (BBB) locomotor scale. Locomotor function recovered progressively during the 6-week postinjury observation period and was significantly greater after x-irradiation (20 Gy) of the injury site or treatment with tempol (275 mg/kg intraperitoneally) than in untreated rats (final BBB Scores 10.6 [x-irradiation treated] and 9.1 [tempol treated] compared with 6.4 [untreated], p < 0.05). Recovery was not significantly improved by HBO (2 atm for 1 hour [BBB Score 8.2, p > 0.05]). Interestingly, the improved recovery of locomotor function after x-irradiation, in contrast with antiproliferative radiotherapy for neoplasia, was inhibited when used together with either HBO or tempol (BBB Scores 8.2 and 8.3, respectively). The ability of tempol to block enhanced locomotor recovery by x-irradiation was accompanied by prevention of alopecia at the irradiation site. The extent of locomotor recovery following treatment with tempol, HBO, and x-irradiation correlated with measurements of spared spinal cord tissue at the contusion epicenter.


CONCLUSIONS
These results suggest that these treatments, when used alone, can activate neuroprotective mechanisms but, in combination, may result in neurotoxicity.
Hillard
Virany H
VH
Department of Neurosurgery, New York Medical College, New York,. USA. hillardv@u.washington.edu
Peng
Hong
H
Das
Kaushik
K
Murali
Raj
R
Moorthy
Chitti R
CR
Etlinger
Joseph D
JD
Zeman
Richard J
RJ
D000505:Alopecia / Q000209:etiology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003131:Combined Modality Therapy; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D005260:Female; D006931:Hyperbaric Oxygenation; D009043:Motor Activity; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects / Q000528:radiation effects; D013113:Spin Labels; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
D000975:Antioxidants; D003497:Cyclic N-Oxides; D013113:Spin Labels; C001803:tempol