Analysis of pathological formation of fiber connection in a rat model of cerebral palsy

对象：脑瘫（CP）发生在大脑发育的早期阶段，表现为痉挛性轻瘫，通常与认知功能障碍有关。CP的现有治疗方法，包括康复、肉毒杆菌毒素、选择性背根切断术和鞘内巴氯芬（ITB），用于管理痉挛状态，不影响运动无力或高级脑功能。在本研究中，我们研究了使用ITB治疗痉挛状态是否也会影响运动功能，使用ITB改善运动能力是否与受损大脑的组织学恢复相关，以及痉挛状态的缓解是否与智力功能的改善相关。对照、CP模型和早期或晚期ITB therapy的CP模型。在CP模型中，出生后第7天（P7）的大鼠在结扎右侧颈总动脉后置于低氧（8%O_2）条件下150 min ...更多信息 动脉在ITB therapy组中，在P21（早期）或P35（晚期）将脊髓导管连接至充满巴氯芬的渗透泵，并置于脊髓蛛网膜下腔。每日12 μ g巴氯芬连续给药，直至P49，治疗28或14天。结果：CP组完成P49横梁行走试验所需的时间与对照组相比显著增加（4.09 ± 0.18秒vs.对照组2.10 ± 0.13秒）。在ITB治疗组中，这被标准化为2.26 ± 0.16秒（早期）和2.52 ± 0.15秒（晚期）。在P49上的径向臂迷宫表现表明，CP组的空间参考记忆恶化（0.85 ± 0.34分，对照组为2.27 ± 0.35分），并且在诱导CP后，工作记忆也下降（0.14 ± 0.18分，对照组为0.64 ± 0.30分）。ITB治疗后，这些功能未恢复。P49时CP组胼胝体厚度为147.9 ± 24.6 μ m，明显小于对照组（446.1 ± 22.1 μ m）。结论：使用ITB治疗痉挛的管理改善了大鼠CP模型的行走能力。这种改善不是由于受损大脑的结构再生，而是由于功能补偿或适应。ITB可将痉挛状态引起的有害感觉和运动刺激降低至更佳水平;这有助于运动功能的恢复。然而，ITB对大鼠CP模型中的智力恢复的作用不充分。少

Object : Cerebral palsy (CP) arises in the early stages of brain development and manifests as spastic paresis that is often associated with cognitive dysfunction. Available treatments for CP, including rehabilitation, botulinum toxin, selective dorsal rhizotomy, and intrathecal baclofen (ITB), are used for the management of spasticity and do not affect motor weakness or higher cerebral function. In this study, we investigated whether the management of spasticity using ITB can also affect motor function, whether improvement in motor ability by the use of ITB is associated with histological recovery of the damaged brain, and whether the release of spasticity is associated with an improvement in intellectual function.Methods : Sprague-Dawley rats were placed into 4 groups : control, CP model, and CP model with either early or late ITB therapy. For the CP model, rats on postnatal day 7 (P7) were placed under hypoxic conditions (8% O_2) for 150 min after ligation of the right common carotid … More artery. In the ITB therapy groups, a spinal catheter was connected to an osmotic pump filled with baclofen and placed in the spinal subarachnoid space on P21 (early) or P35 (late). A daily dose of 12μg of baclofen was continuously administered until P49, resulting in 28 or 14 days of therapy. Changes in spasticity in the CP and CP with ITB treatment groups were confirmed using an evoked potential in the planter muscle.Results : In the CP group, the time required to complete a beam walking test on P49 was significantly increased compared with that in the control group (4.09±0.18 sec vs. 2.10±0.13 sec in the control group). This was normalized to 2.26±0.16 sec (early) and 2.52±0.15 sec (late) in the ITB treatment groups. Radial arm maze performance on P49 indicated that spatial reference memory had deteriorated in the CP group (0.85±0.34 points vs. 2.27±0.35 points in the control group), and working memory was also decreased upon induction of CP (0.14±0.18 points vs. 0.64±0.30 points in the control group). These functions did not recover after ITB treatment. On P49, the thickness of the corpus callosum decreased to 147.9±24.6μm in the CP group ; this was significantly lesser than that in the control group (446.1±22.1μm). The corpus callosum was not restored by ITB treatment.Conclusions : Management of spasticity using ITB therapy improved walking ability in a rat CP model. This improvement was not due to structural regeneration of the damaged brain but due to functional compensation or adaptation. ITB reduces harmful sensory and motor stimulation caused by spasticity to more optimal levels ; this contributes to the recovery of motor function. However, the effect of ITB was not sufficient for intellectual recovery in the rat CP model. Less