Sex may influence motor phenotype in a novel rodent model of cerebral palsy.
Sex may influence motor phenotype in a novel rodent model of cerebral palsy.
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DOI：
10.1016/j.nbd.2019.104711
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发表时间：
2020-02
影响因子：
6.1
通讯作者：
Rutkove, Seward B.
中科院分区：
文献类型：
--
作者：
Aravamuthan, Bhooma R.;Gandham, Sushma;Young, Anne B.;Rutkove, Seward B.
脑性瘫痪（CP）是儿童运动障碍的最常见原因，最常表现为痉挛和/或肌张力障碍。痉挛和肌张力障碍通常是合并症临床严重损伤后，在足月妊娠。目前可用的动物CP模型尚未证明或区分这两种运动表型，限制了它们的临床相关性。我们试图开发一种动物CP模型，显示客观可识别的痉挛和肌张力障碍。我们将出生后第7-8天（相当于人类受孕后37周）的幼鼠暴露于全面缺氧。由于痉挛和肌张力障碍在CP中很难相互区分，因此评估了运动表型的客观电生理标志物。痉挛推断使用电生理测量反射亢进：比目鱼肌霍夫曼反射抑制与2赫兹胫神经刺激。通过计算胫骨前肌和小腿三头肌肌电共激活作为溢出肌肉活动的替代，在不同水平的唤醒下，在自愿等长后肢撤回期间评估肌张力障碍。缺氧影响痉挛和肌张力障碍的措施，在性别依赖的方式。雄性动物的霍夫曼反射抑制减弱，提示痉挛，但拮抗肌共激活无变化。相比之下，雌性动物表现出提示肌张力障碍的共激活增加，但霍夫曼反射抑制无变化。因此，基于性别的电生理学定义的运动表型存在意外分离，男性主要表现为痉挛，女性主要表现为肌张力障碍。这些结果需要人类临床证实，但表明性别可能在新生儿脑损伤的运动表现中发挥关键作用。
Cerebral palsy (CP) is the most common cause of childhood motor disability, manifesting most often as spasticity and/or dystonia. Spasticity and dystonia are often co-morbid clinically following severe injury at term gestation. Currently available animal CP models have not demonstrated or differentiated between these two motor phenotypes, limiting their clinical relevance. We sought to develop an animal CP model displaying objectively identifiable spasticity and dystonia. We exposed rat pups at post-natal day 7–8 (equivalent to human 37 postconceptional weeks) to global hypoxia. Since spasticity and dystonia can be difficult to differentiate from each other in CP, objective electrophysiologic markers of motor phenotypes were assessed. Spasticity was inferred using an electrophysiologic measure of hyperreflexia: soleus Hoffman reflex suppression with 2 Hz tibial nerve stimulation. Dystonia was assessed during voluntary isometric hindlimb withdrawal at different levels of arousal by calculating tibialis anterior and triceps surae electromyographic co-activation as a surrogate of overflow muscle activity. Hypoxia affected spasticity and dystonia measures in a sex-dependent manner. Males had attenuated Hoffman reflex suppression suggestive of spasticity but no change in antagonist muscle co-activation. In contrast, females demonstrated increased co-activation suggestive of dystonia but no change in Hoffman reflex suppression. Therefore, there was an unexpected segregation of electrophysiologically-defined motor phenotypes based on sex with males predominantly demonstrating spasticity and females predominantly demonstrating dystonia. These results require human clinical confirmation but suggest that sex could play a critical role in the motor manifestations of neonatal brain injury.
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影响因子：
8.6
作者：
Albanese, Alberto;Bhatia, Kailash;Bressman, Susan B.;DeLong, Mahlon R.;Fahn, Stanley;Fung, Victor S. C.;Hallett, Mark;Jankovic, Joseph;Jinnah, Hyder A.;Klein, Christine;Lang, Anthony E.;Mink, Jonathan W.;Teller, Jan K.
通讯作者：
Teller, Jan K.
影响因子：
5.3
作者：
Garrison, M. Kevin;Yates, Charlotte C.;Reese, Nancy B.;Skinner, Robert D.;Garcia-Rill, Edgar
通讯作者：
Garcia-Rill, Edgar
影响因子：
9.9
作者：
Ashwal, S;Russman, BS;Stevenson, R
通讯作者：
Stevenson, R
影响因子：
8.6
作者：
KOELMAN, JHTM;WILLEMSE, RB;DEVISSER, BWO
通讯作者：
DEVISSER, BWO
影响因子：
2.5
作者：
DOBBING, J;SANDS, J
通讯作者：
SANDS, J