放射性脑损伤的治疗进展

程锦萍, 李红红, 唐亚梅

PDF(2384 KB)
PDF(2384 KB)
重庆医科大学学报 ›› 2024, Vol. 49 ›› Issue (05) : 610-616. DOI: 10.13406/j.cnki.cyxb.003490
脑损伤和神经系统少罕见病的治疗

放射性脑损伤的治疗进展

作者信息 +

Advances in the treatment of radiation-induced brain injury

Author information +
History +

摘要

放射治疗在控制头颈部肿瘤提高患者生存率的同时,对周围正常脑组织也造成不同程度的损伤,引起放射性脑坏死和认知功能下降,其发生率最高可达90%,严重影响患者的生活质量。研究人员近年来在多个层面上对放射性脑损伤的潜在病因进行了探索,通过筛查和鉴定不同干预靶点,为预防和治疗放射性损伤提供了新的策略。本文对放射性脑损伤的发生发展机制进行了综述,并回顾了现有的药物及非药物干预手段,提出了目前该领域面临的挑战及未来的研究方向。

Abstract

Although radiotherapy can significantly increase the survival rate of patients with head and neck tumors, it also causes damage to the surrounding normal brain tissue, resulting in radiation-induced brain necrosis and cognitive decline, which shows an incidence rate up to 90% and seriously affects the quality of life of patients. In recent years, researchers have explored the potential etiologies of radiation-induced brain injury(RIBI) at various levels and have identified different types of targets for intervention, providing new strategies for the prevention and treatment of radiation-induced damage. This article reviews the mechanisms of the development and progression of RIBI and related pharmaceutical and non-pharmaceutical interventions and proposes the current challenges and future research directions of this field.

关键词

放射性脑损伤 / 发病机制 / 治疗策略

Key words

radiation-induced brain injury / pathogenesis / treatment strategies

中图分类号

R651.1+5

引用本文

导出引用
程锦萍 , 李红红 , 唐亚梅. 放射性脑损伤的治疗进展. 重庆医科大学学报. 2024, 49(05): 610-616 https://doi.org/10.13406/j.cnki.cyxb.003490
Cheng Jinping, Li Honghong, Tang Yamei. Advances in the treatment of radiation-induced brain injury[J]. Journal of Chongqing Medical University. 2024, 49(05): 610-616 https://doi.org/10.13406/j.cnki.cyxb.003490

参考文献

1
Makale MT McDonald CR Hattangadi-Gluth JA,et al. Mechanisms of radiotherapy-associated cognitive disability in patients with brain tumours[J]. Nat Rev Neurol201713(1):52-64.
2
Yoshii Y. Pathological review of late cerebral radionecrosis[J]. Brain Tumor Pathol200825(2):51-58.
3
Santivasi WL Xia F. Ionizing radiation-induced DNA damage,response,and repair[J]. Antioxid Redox Signal201421(2):251-259.
4
Chopp M Chan PH Hsu CY,et al. DNA damage and repair in central nervous system injury:National Institute of Neurological Disorders and Stroke Workshop Summary[J]. Stroke199627(3):363-369.
5
d'Adda Fagagna F. Living on a break:cellular senescence as a DNA-damage response[J]. Nat Rev Cancer20088(7):512-522.
6
Rahmathulla G Marko NF Weil RJ. Cerebral radiation necrosis:a review of the pathobiology,diagnosis and management considerations[J]. J Clin Neurosci201320(4):485-502.
7
Hafner A Bulyk ML Jambhekar A,et al. The multiple mechanisms that regulate p53 activity and cell fate[J]. Nat Rev Mol Cell Biol201920(4):199-210.
8
Vousden KH Lane DP. p53 in health and disease[J]. Nat Rev Mol Cell Biol20078(4):275-283.
9
Xu Y. DNA damage:a trigger of innate immunity but a requirement for adaptive immune homeostasis[J]. Nat Rev Immunol20066(4):261-270.
10
Kam WW Banati RB. Effects of ionizing radiation on mitochondria[J]. Free Radic Biol Med201365:607-619.
11
Cheng JP Jiang JR He BX,et al. A phase 2 study of thalidomide for the treatment of radiation-induced blood-brain barrier injury[J]. Sci Transl Med202315(684):eabm6543.
12
Yang YH Li HH Xu YT,et al. Notch signaling mediates radiation-induced smooth muscle cell hypermuscularization and cerebral vasculopathy[J]. Stroke202253(12):3751-3762.
13
Lumniczky K Szatmári T Sáfrány G. Ionizing radiation-induced immune and inflammatory reactions in the brain[J]. Front Immunol20178:517.
14
Shi ZS Yu P Lin WJ,et al. Microglia drive transient insult-induced brain injury by chemotactic recruitment of CD8+ T lymphocytes[J]. Neuron2023111(5):696-710.
15
Zhang Z Jiang JR He Y,et al. Pregabalin mitigates microglial activation and neuronal injury by inhibiting HMGB1 signaling pathway in radiation-induced brain injury[J]. J Neuroinflammation202219(1):231.
16
Piao JH Major T Auyeung G,et al. Human embryonic stem cell-derived oligodendrocyte progenitors remyelinate the brain and rescue behavioral deficits following radiation[J]. Cell Stem Cell201516(2):198-210.
17
Lee HG Wheeler MA Quintana FJ. Function and therapeutic value of astrocytes in neurological diseases[J]. Nat Rev Drug Discov202221(5):339-358.
18
Monje ML Mizumatsu S Fike JR,et al. Irradiation induces neural precursor-cell dysfunction[J]. Nat Med20028(9):955-962.
19
Monje ML Toda H Palmer TD. Inflammatory blockade restores adult hippocampal neurogenesis[J]. Science2003302(5651):1760-1765.
20
Zhao XH Cheng JP Gui SS,et al. Amifostine-loaded nanocarrier traverses the blood-brain barrier and prevents radiation-induced brain injury[J]. ACS Appl Mater Interfaces202315(12):15203-15219.
21
Lee TC Greene-Schloesser D Payne V,et al. Chronic administration of the angiotensin-converting enzyme inhibitor,ramipril,prevents fractionated whole-brain irradiation-induced perirhinal cortex-dependent cognitive impairment[J]. Radiat Res2012178(1):46-56.
22
Kim JH Brown SL Kolozsvary A,et al. Modification of radiation injury by ramipril,inhibitor of angiotensin-converting enzyme,on optic neuropathy in the rat[J]. Radiat Res2004161(2):137-142.
23
Acharya MM Green KN Allen BD,et al. Elimination of microglia improves cognitive function following cranial irradiation[J]. Sci Rep20166:31545.
24
Ramanan S Kooshki M Zhao WL,et al. The PPARalpha agonist fenofibrate preserves hippocampal neurogenesis and inhibits microglial activation after whole-brain irradiation[J]. Int J Radiat Oncol Biol Phys200975(3):870-877.
25
Zhao WL Payne V Tommasi E,et al. Administration of the peroxisomal proliferator-activated receptor gamma agonist pioglitazone during fractionated brain irradiation prevents radiation-induced cognitive impairment[J]. Int J Radiat Oncol Biol Phys200767(1):6-9.
26
Zhang LY Li K Sun R,et al. Minocycline ameliorates cognitive impairment induced by whole-brain irradiation:an animal study[J]. Radiat Oncol20149:281.
27
Yang RM Duan C Yuan LY,et al. Inhibitors of HIF-1α and CXCR4 mitigate the development of radiation necrosis in mouse brain[J]. Int J Radiat Oncol Biol Phys2018100(4):1016-1025.
28
Jiang XY Perez-Torres CJ Thotala D,et al. A GSK-3β inhibitor protects against radiation necrosis in mouse brain[J]. Int J Radiat Oncol Biol Phys201489(4):714-721.
29
Xu PF Xu YT Hu B,et al. Extracellular ATP enhances radiation-induced brain injury through microglial activation and paracrine signaling via P2X7 receptor[J]. Brain Behav Immun201550:87-100.
30
Peng Y Lu K Li ZC,et al. Blockade of Kv1.3 channels ameliorates radiation-induced brain injury[J]. Neuro Oncol201416(4):528-539.
31
Hladik D Tapio S. Effects of ionizing radiation on the mammalian brain[J]. Mutat Res Rev Mutat Res2016770(Pt B):219-230.
32
Soria B Martin-Montalvo A Aguilera Y,et al. Human mesenchymal stem cells prevent neurological complications of radiotherapy[J]. Front Cell Neurosci201913:204.
33
Wang YX King AD Zhou H,et al. Evolution of radiation-induced brain injury:MR imaging-based study[J]. Radiology2010254(1):210-218.
34
Pan D Rong XM Chen DP,et al. Mortality of early treatment for radiation-induced brain necrosis in head and neck cancer survivors:a multicentre,retrospective,registry-based cohort study[J]. EClinical Medicine202252:101618.
35
Giglio P Gilbert MR. Cerebral radiation necrosis[J]. Neurologist20039(4):180-188.
36
Zhuo XH Huang XL Yan MS,et al. Comparison between high-dose and low-dose intravenous methylprednisolone therapy in patients with brain necrosis after radiotherapy for nasopharyngeal carcinoma[J]. Radiother Oncol2019137:16-23.
37
Cai JH Cheng JP Li HH,et al. A nomogram for the prediction of cerebrovascular disease among patients with brain necrosis after radiotherapy for nasopharyngeal carcinoma[J]. Radiother Oncol2019132:34-41.
38
Tye K Engelhard HH Slavin KV,et al. An analysis of radiation necrosis of the central nervous system treated with bevacizumab[J]. J Neurooncol2014117(2):321-327.
39
Lubelski D Abdullah KG Weil RJ,et al. Bevacizumab for radiation necrosis following treatment of high grade glioma:a systematic review of the literature[J]. J Neurooncol2013115(3):317-322.
40
Chung C Bryant A Brown PD. Interventions for the treatment of brain radionecrosis after radiotherapy or radiosurgery[J]. Cochrane Database Syst Rev20187(7):CD011492.
41
Levin VA Bidaut L Hou P,et al. Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system[J]. Int J Radiat Oncol Biol Phys201179(5):1487-1495.
42
Xu YT Rong XM Hu WH,et al. Bevacizumab monotherapy reduces radiation-induced brain necrosis in nasopharyngeal carcinoma patients:a randomized controlled trial[J]. Int J Radiat Oncol Biol Phys2018101(5):1087-1095.
43
Khan M Zhao ZH Arooj S,et al. Bevacizumab for radiation necrosis following radiotherapy of brain metastatic disease:a systematic review & meta-analysis[J]. BMC Cancer202121(1):167.
44
Dashti SR Spalding A Kadner RJ,et al. Targeted intraarterial anti-VEGF therapy for medically refractory radiation necrosis in the brain[J]. J Neurosurg Pediatr201515(1):20-25.
45
Baroni LV Alderete D Solano-Paez P,et al. Bevacizumab for pediatric radiation necrosis[J]. Neurooncol Pract20207(4):409-414.
46
Cai JH Xue RQ Yue ZW,et al. Neutrophil to lymphocyte ratio as a predictor for treatment of radiation-induced brain necrosis with bevacizumab in nasopharyngeal carcinoma patients[J]. Clin Transl Med202212(1):e583.
47
He L Pi YX Li Y,et al. Efficacy and safety of apatinib for radiation-induced brain injury among patients with head and neck cancer:an open-label,single-arm,phase 2 study[J]. Int J Radiat Oncol Biol Phys2022113(4):796-804.
48
Tang YM Rong XM Hu WH,et al. Effect of edaravone on radiation-induced brain necrosis in patients with nasopharyngeal carcinoma after radiotherapy:a randomized controlled trial[J]. J Neurooncol2014120(2):441-447.
49
Chan AS Cheung MC Law SC,et al. Phase Ⅱ study of alpha-tocopherol in improving the cognitive function of patients with temporal lobe radionecrosis[J]. Cancer2004100(2):398-404.
50
Robinson DM Keating GM. Memantine:a review of its use in Alzheimer's disease[J]. Drugs200666(11):1515-1534.
51
Brown PD Pugh S Laack NN,et al. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy:a randomized,double-blind,placebo-controlled trial[J]. Neuro Oncol201315(10):1429-1437.
52
Cui X Guo YE Fang JH,et al. Donepezil,a drug for Alzheimer's disease,promotes oligodendrocyte generation and remyelination[J]. Acta Pharmacol Sin201940(11):1386-1393.
53
Rapp SR Case LD Peiffer A,et al. Donepezil for irradiated brain tumor survivors:a phase Ⅲ randomized placebo-controlled clinical trial[J]. J Clin Oncol201533(15):1653-1659.
54
Ayoub R Ruddy RM Cox E,et al. Assessment of cognitive and neural recovery in survivors of pediatric brain tumors in a pilot clinical trial using metformin[J]. Nat Med202026(8):1285-1294.
55
Pasquier D Hoelscher T Schmutz J,et al. Hyperbaric oxygen therapy in the treatment of radio-induced lesions in normal tissues:a literature review[J]. Radiother Oncol200472(1):1-13.
56
Wong ST Loo KT Yam KY,et al. Results of excision of cerebral radionecrosis:experience in patients treated with radiation therapy for nasopharyngeal carcinoma[J]. J Neurosurg2010113(2):293-300.
57
Telera S Fabi A Pace A,et al. Radionecrosis induced by stereotactic radiosurgery of brain metastases:results of surgery and outcome of disease[J]. J Neurooncol2013113(2):313-325.

基金

国家杰出青年科学基金资助项目(81925031)
国家自然科学基金重点资助项目(82330099)
国家自然科学基金青年基金资助项目(82304067)

评论

PDF(2384 KB)

Accesses

Citation

Detail

段落导航
相关文章

/