Molecular biology of GAG in the central nerve system and spinal cord injury.

透明质酸是中枢神经系统细胞外基质的一种成分，在神经元周围形成神经周围网。最近有报道称，透明质酸降解酶透明质酸酶促进ampa型谷氨酸受体的侧向移动，增强突触可塑性。然而，透明质酸降解产物（低聚糖）的生物学意义尚未深入研究。本文研究了透明质酸寡糖对大鼠脊髓损伤后运动功能恢复的影响。与由6-12个糖组成的低聚糖不同，双糖HA2，特别是四糖HA4能显著改善运动功能。与这一发现一致，通过皮质脊髓束示踪纤维计数评估，HA4处理增强了轴突再生/发芽。HA4治疗还能显著抑制损伤后两周内iba -1阳性细胞的积累。体外实验表明，HA4能部分阻断nmda诱导的神经元细胞死亡，而其他低聚糖则不能，而蛋白多糖介导的神经突生长抑制不受任何低聚糖处理的影响。综上所述，目前的结果表明，部分由于其神经保护活性，HA4促进脊髓损伤后运动功能的恢复。

Hyaluronan is a component of the extracellular matrix of the central nervous system, and forms perineuronal nets around neurons. It has been recently reported that the hyaluronan-degrading enzyme hyaluronidase promotes lateral mobility of AMPA-type glutamate receptors and enhances synaptic plasticity. However, the biological significance of hyaluronan-degrading products(oligosaccharides) has not been studied in depth. Here we investigated the effects of hyaluronan oligosaccharides on motor function recovery after spinal cord injury in rats. The disaccharide HA2 and especially the tetrasaccharide HA4, significantly improved motor function, unlike the case with oligosaccharides composed of 6-12 saccharides. Consistent with this finding, HA4 treatment enhanced axonal regeneration/sprouting, as assessed by corticospinal tract tracer fiber counts. HA4 treatment also significantly suppressed accumulation of Iba-1-positive cells in a lesion two weeks after injury. In vitro experiments demonstrated that NMDA-induced neuronal cell death was partly blocked by HA4, but not by other oligosaccharides, whereas proteoglycan-mediated inhibition of neurite outgrowth was not affected by treatment with any oligosaccharide examined. Taken together, the present results revealed that due in part to its neuroprotective activity, HA4 promotes motor function recovery after spinal cord injury.