Duhaime Ann-Christine, Saykin Andrew J, McDonald Brenna C, Dodge Carter P, Eskey Clifford J, Darcey Terrance M, Grate Loretta L, Tomashosky Paul
Department of Pediatric Neurosurgery, Children's Hospital at Dartmouth, Dartmouth Hitchcock Medical Center and Dartmouth Medical School, Lebanon, New Hampshire 03756, USA.
J Neurosurg. 2006 Apr;104(4 Suppl):259-64. doi: 10.3171/ped.2006.104.4.259.
The piglet is an excellent model for the developing human brain, and has been used increasingly in various centers for studies of traumatic brain injury and other insults. Unlike rodent or primate models, however, there are few behavioral scales for the piglet, and the available ones are used to test general responsiveness rather than specific functional outcome. The differing behavioral repertoires of animals of different ages provide an additional challenge when age-dependent injury responses are compared. To overcome these experimental limitations of piglets in brain injury research, the authors developed a functional magnetic resonance (fMR) imaging paradigm that can be used to track recovery in the somatosensory cortex over time in anesthetized animals of different ages.
Fifteen fMR imaging studies in eight piglets were performed before and after scaled cortical impact injury to the primary somatosensory cortex subserving snout sensation. Specific anesthetic and imaging protocols enabled visualization of cortical activation, and comparison with somatosensory evoked potentials obtained before and after injury was obtained. A piglet brain template for group-level analysis of these data was constructed, similar to the fMR imaging techniques used in humans, to allow for group comparisons and longitudinal change analysis over time.
Loss of function in a specifically traumatized cortical region and its subsequent recovery over time can now be demonstrated visually by fMR imaging in the piglet. Besides its value in understanding intrinsic recovery mechanisms and plasticity at different ages, this functional outcome measure will enable the use of the piglet model in treatment trials specifically designed for the immature brain.
仔猪是发育中的人类大脑的优秀模型,已在各个中心越来越多地用于创伤性脑损伤和其他损伤的研究。然而,与啮齿动物或灵长类动物模型不同,仔猪的行为量表很少,现有的量表用于测试一般反应性而非特定的功能结果。当比较年龄依赖性损伤反应时,不同年龄动物不同的行为模式带来了额外的挑战。为了克服仔猪在脑损伤研究中的这些实验局限性,作者开发了一种功能磁共振(fMR)成像范式,可用于跟踪不同年龄麻醉动物体感皮层随时间的恢复情况。
对8只仔猪进行了15次fMR成像研究,在对负责口鼻感觉的初级体感皮层进行标准化皮层撞击损伤前后进行。特定的麻醉和成像方案能够可视化皮层激活,并与损伤前后获得的体感诱发电位进行比较。构建了一个用于对这些数据进行组水平分析的仔猪脑模板,类似于人类使用的fMR成像技术,以允许进行组间比较和随时间的纵向变化分析。
现在可以通过fMR成像在仔猪中直观地显示特定创伤皮层区域的功能丧失及其随时间的后续恢复。除了在理解不同年龄的内在恢复机制和可塑性方面的价值外,这种功能结果测量将使仔猪模型能够用于专门为未成熟大脑设计的治疗试验。