Spontaneous corticospinal axonal plasticity and functional recovery after adult central nervous system injury

Although it is believed that little recovery occurs after adult mammalian spinal cord injury, in fact significant spontaneous functional improvement commonly occurs after spinal cord injury in humans. To investigate potential mechanisms underlying spontaneous recovery, lesions of defined components of the corticospinal motor pathway were made in adult rats in the rostral cervical spinal cord or caudal medulla. Following complete lesions of the dorsal corticospinal motor pathway, which contains more than 95% of all corticospinal axons, spontaneous sprouting from the ventral corticospinal tract occurred onto medial motoneuron pools in the cervical spinal cord; this sprouting was paralleled by functional recovery. Combined lesions of both dorsal and ventral corticospinal tract components eliminated sprouting and functional recovery. In addition, functional recovery was also abolished if dorsal corticospinal tract lesions were followed 5 weeks later by ventral corticospinal tract lesions. We found extensive spontaneous structural plasticity as a mechanism correlating with functional recovery in motor systems in the adult central nervous system. Experimental enhancement of spontaneous plasticity may be useful to promote further recovery after adult central nervous system injury.

尽管此前学界普遍认为成年哺乳动物脊髓损伤后几乎无法恢复，但事实上人类脊髓损伤后通常会出现显著的自发性功能改善。为探究自发性恢复的潜在机制，本研究在成年大鼠的颈段脊髓头侧或延髓尾侧制备了皮质脊髓运动通路（corticospinal motor pathway）特定组分的损伤模型。在包含全部皮质脊髓轴突95%以上的背侧皮质脊髓运动通路完全损伤后，腹侧皮质脊髓束（ventral corticospinal tract）向颈段脊髓内侧运动神经元池发生了自发性出芽；该出芽现象与功能恢复同步出现。同时损伤背侧与腹侧皮质脊髓束组分则会消除该出芽与功能恢复。此外，若先制备背侧皮质脊髓束损伤，5周后再实施腹侧皮质脊髓束损伤，功能恢复也会被完全阻断。本研究发现，广泛的自发性结构可塑性（spontaneous structural plasticity）是成年中枢神经系统运动系统中与功能恢复相关的潜在机制；通过实验手段强化自发性可塑性，或可用于促进成年中枢神经系统损伤后的进一步恢复。