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老年大鼠脑出血后瘢痕形成的特征:去铁胺的作用

Characteristics of Scar Formation After Intracerebral Hemorrhage in Aged Rats: Effects of Deferoxamine.

作者信息

Fu Xiongjie, Wan Yingfeng, Hua Ya, Xi Guohua, Keep Richard F

机构信息

Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48109, USA.

出版信息

Cells. 2025 Jul 22;14(15):1127. doi: 10.3390/cells14151127.


DOI:10.3390/cells14151127
PMID:40801561
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12346331/
Abstract

Intracerebral hemorrhage (ICH), a severe stroke subtype common in the elderly, often results in high morbidity and mortality, with limited treatment options for long-term recovery. While glial scar formation is increasingly recognized as key to central nervous system (CNS) repair, its role and characteristics in the aging brain post-ICH remain unclear. This study investigated glial scar formation after ICH (100 μL autologous blood injected into the right basal ganglia model) in aged Fischer 344 rats and assessed the effects of deferoxamine (DFX) treatment. Histological and immunohistochemical analyses were conducted on days 7, 28, and 60 post-ICH using cell-specific and iron-related markers, with DFX administered at 100 mg/kg daily for 14 days in separate groups. Over time, the lesion core showed increased hemosiderin accumulation and astrogliosis. By day 60, the area of astrogliosis corresponded to an area with persistent neuronal loss (DARPP-32-negative). Glial composition shifted from microglia dominance on day 28 to astrocyte predominance by day 60. DFX treatment reduced iron deposition, astrogliosis, and DARPP-32-negative regions while enhancing oligodendrocyte presence. Iron-related markers (HO-1, ferritin, Perls' staining) and PDGFRβ-positive fibrotic cells were concentrated in the scar core. These findings provide novel insights into scar formation after ICH in aged rats and suggest DFX as a potential therapy to improve outcomes in elderly stroke patients.

摘要

脑出血(ICH)是老年人常见的一种严重中风亚型,常导致高发病率和死亡率,长期恢复的治疗选择有限。虽然胶质瘢痕形成越来越被认为是中枢神经系统(CNS)修复的关键,但其在脑出血后衰老大脑中的作用和特征仍不清楚。本研究调查了老年Fischer 344大鼠脑出血(将100μL自体血注入右侧基底神经节模型)后的胶质瘢痕形成情况,并评估了去铁胺(DFX)治疗的效果。在脑出血后第7天、28天和60天,使用细胞特异性和铁相关标记物进行组织学和免疫组化分析,在不同组中,DFX以100mg/kg的剂量每日给药14天。随着时间的推移,病变核心显示含铁血黄素积累增加和星形胶质细胞增生。到第60天,星形胶质细胞增生区域与持续神经元丢失区域(DARPP - 32阴性)相对应。胶质成分从第28天的小胶质细胞占主导转变为第60天的星形胶质细胞占主导。DFX治疗减少了铁沉积、星形胶质细胞增生和DARPP - 32阴性区域,同时增加了少突胶质细胞的存在。铁相关标记物(HO - 1、铁蛋白、Perls染色)和PDGFRβ阳性纤维化细胞集中在瘢痕核心。这些发现为老年大鼠脑出血后的瘢痕形成提供了新的见解,并表明DFX作为一种潜在的治疗方法,可改善老年中风患者的预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c2f/12346331/d98f2ca87f58/cells-14-01127-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c2f/12346331/ada9a4a614b6/cells-14-01127-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c2f/12346331/c01e0aaf3973/cells-14-01127-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c2f/12346331/de1c43fa244e/cells-14-01127-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c2f/12346331/570b7ef7b272/cells-14-01127-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c2f/12346331/9825840e4fad/cells-14-01127-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c2f/12346331/d98f2ca87f58/cells-14-01127-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c2f/12346331/ada9a4a614b6/cells-14-01127-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c2f/12346331/c01e0aaf3973/cells-14-01127-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c2f/12346331/de1c43fa244e/cells-14-01127-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c2f/12346331/570b7ef7b272/cells-14-01127-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c2f/12346331/9825840e4fad/cells-14-01127-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c2f/12346331/d98f2ca87f58/cells-14-01127-g006.jpg

相似文献

[1]
Characteristics of Scar Formation After Intracerebral Hemorrhage in Aged Rats: Effects of Deferoxamine.

Cells. 2025-7-22

[2]
Immune cell response after intracerebral hemorrhage in piglets and the treatment effects of deferoxamine and minocycline.

Exp Neurol. 2025-6-23

[3]
Efficacy of deferoxamine in animal models of intracerebral hemorrhage: a systematic review and stratified meta-analysis.

PLoS One. 2015-5-22

[4]
Human umbilical cord mesenchymal stem cell-derived exosomes inhibit inflammation and fibrotic scar formation after intracerebral hemorrhage.

Mol Cell Biochem. 2025-4-25

[5]
Prescription of Controlled Substances: Benefits and Risks

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[6]
Deferoxamine reduces neuronal death and hematoma lysis after intracerebral hemorrhage in aged rats.

Transl Stroke Res. 2013-10

[7]
Deferasirox for managing iron overload in people with thalassaemia.

Cochrane Database Syst Rev. 2017-8-15

[8]
Deferoxamine therapy for intracerebral hemorrhage: A systematic review.

PLoS One. 2018-3-22

[9]
PPARγ Agonists Accelerate MRI Signal Resolution Mediated by Resting-State Astroglia in Acute Intracerebral Hemorrhage.

Stroke. 2025-9

[10]
miR-210 Regulates Autophagy Through the AMPK/mTOR Signaling Pathway, Reduces Neuronal Cell Death and Inflammatory Responses, and Enhances Functional Recovery Following Cerebral Hemorrhage in Mice.

Neurochem Res. 2025-6-5

本文引用的文献

[1]
A Brief History of Ferritin, an Ancient and Versatile Protein.

Int J Mol Sci. 2024-12-29

[2]
Trial of Early Minimally Invasive Removal of Intracerebral Hemorrhage.

N Engl J Med. 2024-4-11

[3]
Porous Three-Dimensional Polyurethane Scaffolds Promote Scar-Free Endogenous Regeneration After Acute Brain Hemorrhage.

Transl Stroke Res. 2025-4

[4]
Temporal dynamics of microglia-astrocyte interaction in neuroprotective glial scar formation after intracerebral hemorrhage.

J Pharm Anal. 2023-8

[5]
DARPP-32 cells and neuropil define striosomal system and isolated matrix cells in human striatum.

J Comp Neurol. 2023-6

[6]
Intracerebral haemorrhage.

Nat Rev Dis Primers. 2023-3-16

[7]
Iron Neurotoxicity and Protection by Deferoxamine in Intracerebral Hemorrhage.

Front Mol Neurosci. 2022-6-16

[8]
2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association.

Stroke. 2022-7

[9]
Pericyte-derived fibrotic scarring is conserved across diverse central nervous system lesions.

Nat Commun. 2021-9-17

[10]
Seizures and Interictal Epileptiform Activity in the Rat Collagenase Model for Intracerebral Hemorrhage.

Front Neurosci. 2021-6-18

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