Delcour Maxime, Russier Michael, Xin Dong L, Massicotte Vicky S, Barbe Mary F, Coq Jacques-Olivier
UMR 6149 Neurosciences Intégratives et Adaptatives, CNRS, Aix-Marseille Université, Centre Saint Charles, case B, 3 place Victor Hugo, 13331 Marseille Cedex 03, France.
Int J Dev Neurosci. 2011 Oct;29(6):593-607. doi: 10.1016/j.ijdevneu.2011.02.010. Epub 2011 Mar 5.
Early brain injury including white matter damage (WMD) appears strongly correlated to perinatal hypoxia-ischemia and adverse neurological outcomes in preterm survivors. Indeed, WMD has been widely associated with subtle to major motor disturbances, sensory, behavioral and cognitive impairments in preterm infants who afterward develop cerebral palsy (CP). Prenatal ischemia (PI) has been shown to reproduce the main features of WMD observed in preterm infants. The present study was aimed at determining in adult rats the impact of PI on brain axons, musculoskeletal histology and locomotor activity. PI was induced by unilateral intrauterine artery ligation at E17 in pregnant rats. We found axonal degeneration and reactive astrogliosis in several white matter regions of adult PI rats. We found mild myopathic and secondary joint changes, including increased variability in myofiber size in several hind limb muscles, decreased myofibers numbers but increased Pax 7 cells and myofiber size in the gastrocnemius, and mild knee and ankle chondromalacia. Although treadmill locomotion appeared normal, several kinematic parameters, such as stride length, amplitude, velocity and leg joint angles were altered in adult PI rats compared to shams. Using intra- and inter-group variability of kinematic parameters, PI seemed to impair the maturation of locomotion on the treadmill. In addition, PI rats exhibited spontaneous hyperactivity in open-field test. Musculoskeletal changes appeared concomitant with mild impairments in gait and posture. Our rodent model of WMD based on PI reproduces the mild motor deficits and musculoskeletal changes observed in many preterm infants with a perinatal history of hypoxia-ischemia, and contributes towards a better understanding of the interplay between brain injury, musculoskeletal histopathology and gait disturbances encountered subsequently.
早期脑损伤,包括白质损伤(WMD),似乎与早产幸存者的围产期缺氧缺血及不良神经学预后密切相关。事实上,白质损伤与早产婴儿出现的轻微至严重运动障碍、感觉、行为和认知障碍广泛相关,这些婴儿随后会发展为脑瘫(CP)。产前缺血(PI)已被证明可重现早产婴儿中观察到的白质损伤的主要特征。本研究旨在确定成年大鼠中产前缺血对脑轴突、肌肉骨骼组织学和运动活动的影响。通过在怀孕大鼠妊娠第17天进行单侧子宫内动脉结扎来诱导产前缺血。我们在成年产前缺血大鼠的几个白质区域发现了轴突退变和反应性星形胶质细胞增生。我们发现了轻度肌病和继发性关节变化,包括几只后肢肌肉中肌纤维大小变异性增加、肌纤维数量减少,但腓肠肌中Pax 7细胞和肌纤维大小增加,以及轻度膝关节和踝关节软骨软化。尽管跑步机运动看起来正常,但与假手术组相比,成年产前缺血大鼠的几个运动学参数,如步长、幅度、速度和腿部关节角度发生了改变。利用运动学参数的组内和组间变异性,产前缺血似乎损害了跑步机上运动的成熟度。此外,产前缺血大鼠在旷场试验中表现出自发性多动。肌肉骨骼变化似乎与步态和姿势的轻度损伤同时出现。我们基于产前缺血的白质损伤啮齿动物模型重现了许多有围产期缺氧缺血病史的早产婴儿中观察到的轻度运动缺陷和肌肉骨骼变化,并有助于更好地理解随后遇到的脑损伤、肌肉骨骼组织病理学和步态障碍之间的相互作用。