Aszmann Oskar C, Winkler Tobias, Korak Klaus, Lassmann Hans, Frey Manfred
Division of Plastic and Reconstructive Surgery, Department of Surgery, University Clinics of Vienna School of Medicine, Waehringer Guertel 18-20, 1090 Vienna, Austria.
Neurol Res. 2004 Mar;26(2):211-7. doi: 10.1179/016164104225013789.
Injuries of the peripheral nerve in the early post-natal period are known to cause massive loss in the motoneuron pools of the spinal cord. However, the exact time frame and extent of motoneuron death in the cervical spinal cord after a brachial plexus lesion and the altered course after neuroprotection with different trophic factors is not known. In the present study, the time course of induced motoneuron death after a neonatal peripheral nerve injury and the effect of GDNF was investigated over a 4 week time period to determine the window of opportunity for possible therapeutic interventions in obstetrical plexus palsy. The brachial plexus of a total of 70 animals was explored within 12 hours after birth and divided at trunc level. The plexus was then labeled with a fluorescent tracer to identify the corresponding motoneuron pool. Two groups were prepared: Group I remained untreated to assess the natural course of induced neuronal death. Group II received GDNF immediately after the lesion. Post-operatively the animals were evaluated sequentially over 29 days. Surviving motoneurons were evaluated quantitatively counting the nucleoli. The entire brachial plexus of the rat is supplied by a total of about 4000 motoneurons. After injury the number of motoneurons steadily diminished within the first 10 days to reach a plateau of about 20% of the original number. At this time the GDNF treated group still had 85% (3330 +/- 247) of motoneurons viable. This further decreased so that at the termination of the experiment at day 29 there were still 2527 +/- 285 motoneurons alive. This study clearly shows that pathology after a brachial plexus injury in the newborn is not restricted to the peripheral nerve alone. In this model 64% of motoneurons underwent apoptosis within the first week after injury, reaching a plateau after 10 days at 20%. GDNF successfully rescued motoneurons so that after 4 weeks still 65% were present. We conclude that GDNF leads to enhanced motoneuron survival so that exogenous trophic support of motoneurons might have a role in the treatment of all types of severe neonatal plexopathies, maintaining the viability of motoneurons until reconstructive surgery provides them with a pathway for regeneration and endogenous trophic support.
已知出生后早期的周围神经损伤会导致脊髓运动神经元池大量减少。然而，臂丛神经损伤后颈脊髓运动神经元死亡的确切时间范围和程度，以及不同营养因子进行神经保护后的变化过程尚不清楚。在本研究中，对新生儿周围神经损伤后诱导的运动神经元死亡的时间进程以及胶质细胞源性神经营养因子（GDNF）的作用进行了为期4周的研究，以确定在产瘫中可能进行治疗干预的时机窗口。在出生后12小时内对总共70只动物的臂丛神经进行探查，并在截断水平进行划分。然后用荧光示踪剂标记臂丛神经，以识别相应的运动神经元池。制备了两组：第一组不进行治疗，以评估诱导神经元死亡的自然进程。第二组在损伤后立即给予GDNF。术后对动物进行为期29天的连续评估。通过定量计数核仁来评估存活的运动神经元。大鼠的整个臂丛神经由总共约4000个运动神经元供应。损伤后，运动神经元的数量在最初10天内稳步减少，达到约原始数量20%的平台期。此时，GDNF治疗组仍有85%（3330±247）的运动神经元存活。这一数量进一步减少，以至于在实验第29天结束时，仍有2527±285个运动神经元存活。这项研究清楚地表明，新生儿臂丛神经损伤后的病理变化不仅限于周围神经。在这个模型中，64%的运动神经元在损伤后第一周内发生凋亡，10天后达到20%的平台期。GDNF成功挽救了运动神经元，以至于4周后仍有65%存在。我们得出结论，GDNF可提高运动神经元的存活率，因此外源性营养支持运动神经元可能在治疗所有类型的严重新生儿丛病中发挥作用，在重建手术为它们提供再生途径和内源性营养支持之前维持运动神经元的活力。
