Gramsbergen Albert
Medical Physiology, University of Groningen, Ant. Deusinglaan 1, Groningen, The Netherlands.
Neurosci Biobehav Rev. 2007;31(8):1088-94. doi: 10.1016/j.neubiorev.2007.10.002.
The widely held view, known as Kennard's principle, that lesions in the human central nervous system in the perinatal period are followed by better compensation than equivalent lesions sustained at a later age is under challenge from results of animal experiments. Experiment in rats have demonstrated, contrastingly, that lesions at early stages generally lead to more behavioral impairments than lesions of a similar size and location at adult stages. It also has been demonstrated that early lesions often lead to extensive neural reorganizations. Certain experiments even indicated that the extent of these reorganizations (e.g., after lesions in the motor cortex or the cerebellum) is inversely related to the degree of behavioral compensation. The question arises, why there is a discrepancy between the results in the human, suggesting enhanced functional recovery after lesions at perinatal ages, and those from animal experiments? One explanation is that lesions in animal experiments often are much larger than those occurring in the human. Secondly, the timing of the insult relative to the brain development seems to be critical. For each neural system a specific relation seems to exist between the timing of the insult, the degree of the neuronal reorganization and the behavioral consequences. Results from experimental research have suggested that the recruitment of stem cells in the brain after early lesions in certain regions might play a role in the repair of lesioned areas and also, that stem cells might play a role in the rescue of compromised cells. Ultimately such therapies might help to alleviate the consequences of perinatal brain lesions in the human.
一种被广泛接受的观点,即所谓的肯纳德原则,认为围产期人类中枢神经系统受损后的代偿情况优于在较晚年龄遭受的同等损伤,这一观点正受到动物实验结果的挑战。相反,对大鼠的实验表明,早期损伤通常比成年期类似大小和位置的损伤导致更多的行为障碍。研究还表明,早期损伤常导致广泛的神经重组。某些实验甚至表明,这些重组的程度(例如,在运动皮层或小脑损伤后)与行为代偿程度呈负相关。问题来了,为什么人类实验结果表明围产期损伤后功能恢复增强,而动物实验结果却不同呢?一种解释是,动物实验中的损伤往往比人类发生的损伤大得多。其次,相对于大脑发育而言,损伤的时间似乎至关重要。对于每个神经系统,损伤时间、神经元重组程度和行为后果之间似乎都存在特定的关系。实验研究结果表明,某些区域早期损伤后大脑中干细胞的募集可能在损伤区域的修复中起作用,而且干细胞可能在挽救受损细胞方面发挥作用。最终,此类疗法可能有助于减轻人类围产期脑损伤的后果。