Preliminary trial of neuronal regeneration with the olfactory mucosa using rat model

为了制作大鼠完整的脊髓损伤模型，横切脊髓T10水平，在其上做约1.5 mm的间隙。这个手术可以使几乎完全截瘫至少持续10周。首先，在脊髓移植后立即移植同种嗅粘膜。与呼吸粘膜移植对照组相比，治疗组移植后束缚肢运动活动明显改善，但BBB评分略有改善。组织学分析显示，移植部位检测到来自嗅粘膜的p75NGFR阳性细胞。为结束人体试验的临床情况，我们在大鼠脊髓交易后2周移植嗅粘膜。该模型后肢行为恢复也有明显改善。但这种恢复是有限的，因为它们的后肢无法支撑它们的体重。他们恢复膀胱功能以诱导自愿收缩。组织学观察显示，嗅觉黏膜移植组移植部位吻侧脊髓空腔形成明显少于对照组。对照组脊髓尾端萎缩。移植部位检测到p75NGFR和GFAP双阳性细胞，提示这些细胞有助于轴突再生。将BDA注射到移植大鼠的大脑感觉运动皮层，检测皮质-脊髓束。注射后2周，在脊髓尾部发现BDA，对照组未发现BDA。这些数据表明，嗅觉粘膜可以帮助轴突再生，但不足以恢复完全性脊髓损伤后的有用运动。

To make the complete spinal cord injury model in the rat, the T10 level of spinal cord was transected and about 1.5 mm gap was made there. This procedure makes almost complete paraplegia at least for 10 weeks. At first, syngenic olfactory mucosa was transplanted just after the transaction of spinal cord. Compared to the respiratory mucosa transplanted control group, the locomotor activity of bind limbs in treated group was significantly but slight improved in BBB score after transplantation. Histological analysis showed that p75NGFR positive cells, which was delivered from olfactory mucosa, is detected in the transplanted site.To close, the clinical situation of human trial, we transplanted olfactory mucosa 2 weeks after rat spinal cord transaction. This model also showed significant improvement of behavior recovery of hind limbs. But this recovery is limited, as they could not support their weight with hind limbs. They recovered bladder function to induce voluntary contraction. Histological assessment showed that cavity formation in the rostral spinal cords of the transplanted site was smaller in the olfactory mucosa transplanted group than the control group. Caudal spinal cord was atrophic in the control group. p75NGFR and GFAP double positive cells were detected in the transplanted site and these cells suggested to help regeneration of axonal regeneration. BDA was injected to the cerebral sensory motor cortex of the transplanted rats to detect the cortico-spinal tract. BDA was found in the caudal spinal cord 2 weeks after injection, which was not detected in the control group.These data suggest that olfactory mucosa could help axonal regeneration but it is not enough to recover the useful movement after complete spinal cord injuy.