Linolenic acid prevents neuronal cell death and paraplegia after transient spinal cord ischemia in rats.
OBJECTIVE
Spinal cord ischemia is a devastating complication of thoracic and thoracoabdominal aortic surgery. Recent studies have suggested a neuroprotective effect of polyunsaturated fatty acids against cerebral ischemia. We investigated the effect of linolenic acid (LIN) in a rat model of spinal cord ischemia.


METHODS
Rats were subjected to cross-clamping of the aortic arch and left subclavian artery for 14 minutes. Groups were as follows: sham operation (n = 15); ischemia (n = 15), receiving only vehicle; LIN A (n = 15), receiving LIN before clamping; and LIN B (n = 15), receiving LIN at onset of reperfusion. Neurologic status was assessed daily for 7 days. Spinal cords were harvested for histopathologic analysis, TUNEL staining, and immunohistochemistry for Bax, heat shock protein 70 (HSP70), and nuclear factor-kappaB.


RESULTS
Ischemic rats had severe and definitive paraplegia. LIN-treated rats had significantly better neurologic function. Histopathologic analysis disclosed severe neuronal necrosis in the lumbar gray matter of ischemic rats, whereas most of the LIN-treated rats sustained mild to moderate injury. LIN reduced the loss of motor neurons at 7 days (LIN A, 17 +/- 6, and LIN B, 15 +/- 7, versus ischemia, 6 +/- 2 per section; P <.05). LIN prevented apoptotic neuronal cell death, Bax immunoreactivity of the pro-apoptotic protein Bax, and the nuclear transcription factor NF-kappaB. Nuclear HSP70 immunoreactivity was noted exclusively in motor neurons from LIN-treated rats and not in motor neurons from ischemic rats.


CONCLUSIONS
These results suggest that LIN can induce protection against ischemia in the spinal cord, thereby preventing both necrosis and apoptosis of motor neurons.
Lang-Lazdunski
Loïc
L
Department of Thoracic Surgery, Hôpital d'Instruction des Armées PercyValbonne, France.
Blondeau
Nicolas
N
Jarretou
Gisèle
G
Lazdunski
Michel
M
Heurteaux
Catherine
C
D000704:Analysis of Variance; D000818:Animals; D001707:Biopsy, Needle; D016923:Cell Death / Q000187:drug effects*; D004195:Disease Models, Animal; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D010264:Paraplegia / Q000188:drug therapy* / Q000209:etiology; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D020760:Spinal Cord Ischemia / Q000150:complications / Q000473:pathology*; D018709:Statistics, Nonparametric; D017962:alpha-Linolenic Acid / Q000494:pharmacology*
D018840:HSP70 Heat-Shock Proteins; D018696:Neuroprotective Agents; D017962:alpha-Linolenic Acid