Acute motor deficit and subsequent remyelination-associated recovery following internal capsule demyelination in mice.
Acute motor deficit and subsequent remyelination-associated recovery following internal capsule demyelination in mice.
复制标题
小鼠内囊脱髓鞘后急性运动缺陷和随后的髓鞘再生相关恢复。
DOI：
10.1111/jnc.15142
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发表时间：
2021-03
影响因子：
4.7
通讯作者：
Huang JK
中科院分区：
文献类型：
--
作者：
Yamazaki R;Ohno N;Huang JK
多发性硬化症是一种慢性炎症性脱髓鞘性中枢神经系统疾病，其特征是运动功能障碍。然而，髓鞘再生是否促进脱髓鞘损伤后的运动恢复仍不清楚。内囊（IC）的损伤已知会导致多发性硬化症和中风的运动障碍。在这里，我们诱导局灶性IC脱髓鞘小鼠注射溶血磷脂酰胆碱（LPC），并检查其对运动行为的影响。我们还比较了LPC诱导的IC损伤与内皮素-1（ET 1）（一种用于实验性卒中病变的强效血管收缩剂）产生的IC损伤的作用。我们发现LPC或ET 1注射在损伤后7天（dpl）诱导不对称运动缺陷，并且两种损伤类型均显示出小胶质细胞/巨噬细胞密度增加、髓鞘丢失和轴突营养不良。注射ET 1的小鼠在第28天仍存在运动缺陷和病变病理学。相比之下，LPC注射小鼠在28 dpl时恢复运动功能，活化的小胶质细胞/巨噬细胞密度相应降低，髓鞘染色和损伤中轴突完整性恢复。这些结果表明LPC诱导的IC脱髓鞘导致急性运动缺陷和随后通过髓鞘再生恢复，并可用于补充未来的药物筛选，以确定促进髓鞘再生的药物。在这个问题上，我们研究了局灶性内囊（IC）脱髓鞘对小鼠运动行为的影响。我们发现，溶血磷脂酰胆碱（LPC）诱导的IC脱髓鞘导致急性不对称运动缺陷，随后是髓鞘再生相关的功能恢复。我们的研究结果表明，IC脱髓鞘是一种易于处理的模型，通过行为测量来表征脱髓鞘和髓鞘再生，并可用于补充未来的药物发现工作，以促进炎症性脱髓鞘疾病，如多发性硬化症（MS）的修复。使用BioRender生成的图像。
Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system (CNS), characterized by accumulated motor disability. However, whether remyelination promotes motor recovery following demyelinating injury remains unclear. Damage to the internal capsule (IC) is known to result in motor impairment in multiple sclerosis and stroke. Here, we induced focal IC demyelination in mice by lysophosphatidylcholine (LPC) injection, and examined its effect on motor behavior. We also compared the effect of LPC‐induced IC damage to that produced by endothelin‐1 (ET1), a potent vasoconstrictor used in experimental stroke lesions. We found that LPC or ET1 injections induced asymmetric motor deficit at 7 days post‐lesion (dpl), and that both lesion types displayed increased microglia/macrophage density, myelin loss, and axonal dystrophy. The motor deficit and lesion pathology remained in ET1‐injected mice at 28 dpl. In contrast, LPC‐injected mice regained motor function by 28 dpl, with corresponding reduction in activated microglia/macrophage density, and recovery of myelin staining and axonal integrity in lesions. These results suggest that LPC‐induced IC demyelination results in acute motor deficit and subsequent recovery through remyelination, and may be used to complement future drug screens to identify drugs for promoting remyelination. In this issue, we examined the effect of focal internal capsule (IC) demyelination on motor behavior in mice. We found that lysophosphatidylcholine (LPC) induced demyelination at the IC resulted in acute asymmetric motor deficit, followed by subsequent remyelination‐associated functional recovery. Our results suggest that IC demyelination is a tractable model for characterizing demyelination and remyelination through behavioral measurements, and may be used to complement future drug discovery efforts for promoting repair in inflammatory demyelinating disorders, such as multiple sclerosis (MS). Images generated with BioRender.
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影响因子：
--
作者：
Lee, MA;Blamire, AM;Matthews, PM
通讯作者：
Matthews, PM
影响因子：
3
作者：
Roome, R. Brian;Bartlett, Robert F.;Vanderluit, Jacqueline L.
通讯作者：
Vanderluit, Jacqueline L.
DOI：
10.1056/nejmra1401483
发表时间：
2018-01-11
期刊：
The New England journal of medicine
影响因子：
--
作者：
Reich DS;Lucchinetti CF;Calabresi PA
通讯作者：
Calabresi PA
影响因子：
3
作者：
Metz, GA;Whishaw, IQ
通讯作者：
Whishaw, IQ
影响因子：
3
作者：
Rabl, R.;Horvath, A.;Hutter-Paier, B.
通讯作者：
Hutter-Paier, B.