Genetic Deletion of Paired Immunoglobulin-Like Receptor B Does Not Promote Axonal Plasticity or Functional Recovery after Traumatic Brain Injury
Genetic Deletion of Paired Immunoglobulin-Like Receptor B Does Not Promote Axonal Plasticity or Functional Recovery after Traumatic Brain Injury
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DOI：
10.1523/jneurosci.3228-10.2010
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发表时间：
2010-09-29
影响因子：
5.3
通讯作者：
Yamashita, Toshihide
中科院分区：
文献类型：
--
作者：
Omoto, Shusaku;Ueno, Masaki;Yamashita, Toshihide
神经网络的重新布线是恢复脑损伤后行为功能的基本步骤。然而，成人中枢神经系统的轴突可塑性潜力有限。髓鞘相关蛋白Nogo、髓鞘相关糖蛋白(MAG)和少突胶质细胞髓磷脂糖蛋白(OMGp)可抑制轴突的可塑性，因此靶向它们参与的抑制通路是促进可塑性和功能恢复的潜在手段。Nogo、MAG和OMgp都与Nogo受体(NGR)和配对的免疫球蛋白样受体B(PirB)相互作用。在这里，我们确定了阻断PirB活性是否能促进皮质损伤后轴突的重组和功能恢复。我们发现，一侧运动皮质损伤后，对侧皮质脊髓束轴突发芽进入失神经的颈髓一侧。这种轴突重组的程度在出生后早期受损的小鼠中比在髓鞘开始形成时受损的小鼠要大得多。这表明髓鞘相关蛋白可能限制了体内轴突的重塑。然而，在PirB(-/-)小鼠中，皮质脊髓束或皮质脊髓束内发芽的纤维数量并没有增加。通过三次运动测试，阻断PirB信号也未能促进功能恢复。我们的结果表明，阻断PirB的功能不足以促进皮质损伤后轴突的重组或功能恢复。
The rewiring of neural networks is a fundamental step in recovering behavioral functions after brain injury. However, there is limited potential for axonal plasticity in the adult CNS. The myelin-associated proteins Nogo, myelin-associated glycoprotein (MAG), and oligodendrocyte myelin glycoprotein (OMgp) are known to inhibit axonal plasticity, and thus targeting the inhibitory pathways they participate in is a potential means of promoting plasticity and functional recovery. Each of Nogo, MAG, and OMgp interacts with both the Nogo receptor (NgR) and paired immunoglobulin-like receptor B (PirB). Here, we determined whether blocking PirB activity enhances axonal reorganization and functional recovery after cortical injury. We found that axons of the contralesional corticospinal tract sprouted into the denervated side of the cervical spinal cord after unilateral injury of the motor cortex. The extent to which this axonal reorganization occurred was far greater in mice lesioned during early postnatal days than in mice lesioned at an age when myelin had begun to form. This suggests that myelin-associated proteins might limit axonal remodeling in vivo. However, the number of sprouting fibers within either the corticospinal or corticorubral tract was not enhanced in PirB(-/-) mice. Blocking PirB signaling also failed to enhance functional recovery with three motor tests. Our results suggest that blocking the function of PirB is not sufficient to promote axonal reorganization or functional recovery after cortical injury.