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脊髓脊膜膨出患儿血浆 GDNF 水平及其与神经功能损害的关系:一项即时检测研究。

Plasma GDNF levels in spinal dysraphism and its relation with neurological impairment in children: A point of care study.

机构信息

Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi, 110029, India.

Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, 110029, India.

出版信息

J Pediatr Urol. 2024 Feb;20(1):46.e1-46.e8. doi: 10.1016/j.jpurol.2023.09.019. Epub 2023 Oct 5.

Abstract

AIMS

GDNF plays a crucial role in the stimulation of recovery, neuroplasticity and synaptic reorganization after spinal cord injury providing neuroprotection and neuroregeneration. Plasma GDNF levels are upregulated in cases of spina bifida owing to the intrauterine damage of the exposed spinal cord. Our aim was to compare the plasma GDNF levels in patients of spina bifida with non-spina bifida cases and assess the correlation with neurological impairment at one year of follow up.

METHODS

Single centre prospective analysis of cases of spina bifida from 2020 to 2022 at presentation and after one year of follow up post-surgery. Cases with hernia and hydrocele without any other disorders were recruited into the control group. Plasma GDNF levels were assessed with immunoassay kits and compared with neurological involvement.

RESULTS

85 cases were included in the study. GDNF levels were elevated in cases compared to controls (mean 6.62 vs 1.76) with significant p value (<0.01). Same was observed for open and closed defects (mean 7.63 vs 4.86: p < 0.01). At follow up of 52 cases post-surgery cases with neurogenic bladder with abnormal urodynamic studies, sphincter involvement and motor impairment had significantly elevated baseline levels of GDNF compared with those who did not have this neurological impairment (p < 0.01).

DISCUSSION

The neurotrophic factor up-regulation can reflect an endogenous attempt at neuroprotection against the biochemical and molecular cascades triggered by the spinal cord damage. This upregulation can be represented as important biochemical markers of severe spinal cord damage and can be associated with severity of spine injury in MMC patients. Our results are in keeping with these findings, that, there were increased levels of plasma GDNF levels in cases of spinal dysraphism compared to control population. Also, the type of lesion reflecting the severity whether a closed or an open dysraphism, showed significant difference in levels between them suggesting, yet again, more damage in open defect as expected. The levels were higher with involvement of bladder, sphincter and lower limb power.

CONCLUSION

There is significant elevation of plasma GDNF levels in cases of spina bifida and this elevation is proportional to the degree of spinal damage and hence the neurological impairment. GDNF levels are a good predictor for assessing the severity of the lesion and thus the outcome in these cases. Additional prospective and long-term studies with a larger cohort are needed for a better understanding of neurotrophin pattern modulation in MMC.

摘要

目的

GDNF 在脊髓损伤后的恢复、神经可塑性和突触重排中发挥关键作用,提供神经保护和神经再生。由于暴露的脊髓在子宫内受损,脊柱裂患者的血浆 GDNF 水平升高。我们的目的是比较脊柱裂患者和非脊柱裂患者的血浆 GDNF 水平,并评估其与一年随访时的神经损伤的相关性。

方法

对 2020 年至 2022 年在我院就诊的脊柱裂患者进行单中心前瞻性分析,并在手术后一年进行随访。招募无其他疾病的疝和阴囊积水患者作为对照组。采用免疫试剂盒检测血浆 GDNF 水平,并与神经受累情况进行比较。

结果

85 例患者纳入研究。与对照组相比,病例组 GDNF 水平升高(平均 6.62 比 1.76,p 值<0.01)。开放性和闭合性缺损组也是如此(平均 7.63 比 4.86,p<0.01)。术后 52 例随访的神经源性膀胱患者,存在异常尿动力学研究、括约肌受累和运动障碍,其 GDNF 基线水平明显高于无神经功能障碍的患者(p<0.01)。

讨论

神经营养因子的上调可以反映内源性的神经保护作用,对抗脊髓损伤引发的生化和分子级联反应。这种上调可以作为严重脊髓损伤的重要生化标志物,并与 MMC 患者脊柱损伤的严重程度相关。我们的研究结果与这些发现一致,即与对照组相比,脊柱发育不良患者的血浆 GDNF 水平升高。此外,反映损伤严重程度的病变类型,无论是闭合性还是开放性脊柱发育不良,两者之间的水平存在显著差异,这再次表明开放性缺损的损伤更严重,这是预期的结果。当涉及膀胱、括约肌和下肢力量时,水平更高。

结论

脊柱裂患者的血浆 GDNF 水平显著升高,且这种升高与脊髓损伤程度成正比,进而与神经损伤程度成正比。GDNF 水平是评估病变严重程度和因此评估这些患者预后的良好预测因子。需要更多前瞻性和长期研究,纳入更大的队列,以更好地了解 MMC 中神经营养因子模式的调节。

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