Linolenic acid prevents neuronal cell death and paraplegia after transient spinal cord ischemia in rats

被引:83
作者
Lang-Lazdunski, L
Blondeau, N
Jarretou, G
Lazdunski, M
Heurteaux, C
机构
[1] CNRS, Inst Pharmacol Mol & Cellulaire, UMR 6097, Inst Paul Hamel, F-06560 Valbonne, France
[2] Hop Instruct Armees Percy, Dept Thorac Surg, Clamart, France
关键词
D O I
10.1016/S0741-5214(03)00473-7
中图分类号
R61 [外科手术学];
学科分类号
摘要
Purpose: 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. Conclusion: These results suggest that LIN can induce protection against ischemia in the spinal cord, thereby preventing both necrosis and apoptosis of motor neurons.
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页码:564 / 575
页数:12
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