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脑与脊髓创伤:我们对胰岛素生长因子1基因治疗的治疗潜力的了解。

Brain and spinal cord trauma: what we know about the therapeutic potential of insulin growth factor 1 gene therapy.

作者信息

Bellini María Jose, Labombarda Florencia

机构信息

Lab de Bioquímica del Envejecimiento, INIBIOLP- CONICET, Facultad de Ciencias Medicina, Universidad Nacional de La Plata, La Plata, Argentina.

Laboratory of Neuroendocrine Biochemistry, IBYME-CONICET; Department of Human Biochemistry, Faculty of Medicine, Universidad de Buenos Aires, Buenos Aires, Argentina.

出版信息

Neural Regen Res. 2023 Feb;18(2):253-257. doi: 10.4103/1673-5374.343902.

Abstract

Although little attention has been paid to cognitive and emotional dysfunctions observed in patients after spinal cord injury, several reports have described impairments in cognitive abilities. Our group also has contributed significantly to the study of cognitive impairments in a rat model of spinal cord injury. These findings are very significant because they demonstrate that cognitive and mood deficits are not induced by lifestyle changes, drugs of abuse, and combined medication. They are related to changes in brain structures involved in cognition and emotion, such as the hippocampus. Chronic spinal cord injury decreases neurogenesis, enhances glial reactivity leading to hippocampal neuroinflammation, and triggers cognitive deficits. These brain distal abnormalities are recently called tertiary damage. Given that there is no treatment for Tertiary Damage, insulin growth factor 1 gene therapy emerges as a good candidate. Insulin growth factor 1 gene therapy recovers neurogenesis and induces the polarization from pro-inflammatory towards anti-inflammatory microglial phenotypes, which represents a potential strategy to treat the neuroinflammation that supports tertiary damage. Insulin growth factor 1 gene therapy can be extended to other central nervous system pathologies such as traumatic brain injury where the neuroinflammatory component is crucial. Insulin growth factor 1 gene therapy could emerge as a new therapeutic strategy for treating traumatic brain injury and spinal cord injury.

摘要

尽管脊髓损伤患者出现的认知和情感功能障碍很少受到关注,但已有几份报告描述了认知能力受损的情况。我们团队也在脊髓损伤大鼠模型的认知障碍研究方面做出了重大贡献。这些发现非常重要,因为它们表明认知和情绪缺陷不是由生活方式改变、滥用药物及联合用药引起的。它们与涉及认知和情绪的脑结构变化有关,比如海马体。慢性脊髓损伤会减少神经发生,增强胶质细胞反应性导致海马体神经炎症,并引发认知缺陷。这些脑远端异常最近被称为三级损伤。鉴于目前尚无针对三级损伤的治疗方法,胰岛素生长因子1基因疗法成为一个不错的选择。胰岛素生长因子1基因疗法可恢复神经发生,并诱导小胶质细胞表型从促炎向抗炎极化,这代表了一种治疗支持三级损伤的神经炎症的潜在策略。胰岛素生长因子1基因疗法可扩展至其他中枢神经系统疾病,如神经炎症成分至关重要的创伤性脑损伤。胰岛素生长因子1基因疗法可能成为治疗创伤性脑损伤和脊髓损伤的一种新治疗策略。

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