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

在T10节段切断脊髓，造成1.5mm左右的间隙，制作大鼠完全性脊髓损伤模型。这种手术使几乎完全截瘫至少10周。首先，在脊髓切断后立即移植同系嗅粘膜。与呼吸道粘膜移植对照组相比，治疗组移植后患肢的运动功能明显改善，但BBB评分改善不明显。组织学分析显示，移植部位可见p75NGFR阳性细胞，其来源于嗅粘膜。为了接近人体实验的临床情况，我们在大鼠脊髓损伤后2周移植嗅粘膜。该模型还显示出显著改善的后肢行为恢复。但这种恢复是有限的，因为它们无法用后肢支撑体重。他们恢复膀胱功能，诱导自主收缩。组织学检查显示，嗅粘膜移植组移植部位的头端脊髓中的空洞形成比对照组小。对照组尾侧脊髓萎缩。在移植部位检测到p75NGFR和GFAP双阳性细胞，这些细胞可能有助于轴突再生。将BDA注射到移植大鼠的大脑感觉运动皮层，以检测皮质脊髓束。注射后2周，在脊髓尾侧可见BDA，而对照组未见BDA，提示嗅粘膜能促进轴突再生，但不足以恢复脊髓完全损伤后的有用运动。

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.