Microglia As Therapeutic Target for Radiation-Induced Brain Injury

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Aug 12

PMID 35955439

Authors

Qun Liu

Yan Huang

Mengyun Duan

Qun Yang

Boxu Ren

Fengru Tang

Affiliations

Soon will be listed here.

Abstract

Radiation-induced brain injury (RIBI) after radiotherapy has become an increasingly important factor affecting the prognosis of patients with head and neck tumor. With the delivery of high doses of radiation to brain tissue, microglia rapidly transit to a pro-inflammatory phenotype, upregulate phagocytic machinery, and reduce the release of neurotrophic factors. Persistently activated microglia mediate the progression of chronic neuroinflammation, which may inhibit brain neurogenesis leading to the occurrence of neurocognitive disorders at the advanced stage of RIBI. Fully understanding the microglial pathophysiology and cellular and molecular mechanisms after irradiation may facilitate the development of novel therapy by targeting microglia to prevent RIBI and subsequent neurological and neuropsychiatric disorders.

Citing Articles

Intranasal delivery of AEP inhibitor-loaded neuron-targeted liposome ameliorates radiation-induced brain injury.

Liao K, Gao Y, Cheng M, Zhang Y, Zhao J, Zhou L Mater Today Bio. 2025; 31:101568.

PMID: 40026629 PMC: 11872414. DOI: 10.1016/j.mtbio.2025.101568.

Central Nervous System Response Against Ionizing Radiation Exposure: Cellular, Biochemical, and Molecular Perspectives.

Kumar R, Kumari P, Kumar R Mol Neurobiol. 2025; .

PMID: 39875779 DOI: 10.1007/s12035-025-04712-z.

The current research status of the mechanisms and treatment of radioactive brain injury.

Wang Y, Bao X, Zhang Y, Wu Q Am J Cancer Res. 2025; 14(12):5598-5613.

PMID: 39803653 PMC: 11711531. DOI: 10.62347/BEAU4974.

Structural and functional changes in the hippocampus induced by environmental exposures.

Albadawi E Neurosciences (Riyadh). 2025; 30(1):5-19.

PMID: 39800422 PMC: 11753596. DOI: 10.17712/nsj.2025.1.20240052.

Hyperbaric oxygen therapy attenuates brain radiation-induced cognitive deficits in rats.

Ho S, Lin C, Huang C, Lin C, Lin M, Wang Y Int J Med Sci. 2025; 22(2):283-297.

PMID: 39781518 PMC: 11704689. DOI: 10.7150/ijms.104248.

References

Azrad M, Zeineh N, Weizman A, Veenman L, Gavish M . The TSPO Ligands 2-Cl-MGV-1, MGV-1, and PK11195 Differentially Suppress the Inflammatory Response of BV-2 Microglial Cell to LPS. Int J Mol Sci. 2019; 20(3). PMC: 6387401. DOI: 10.3390/ijms20030594. View

Ueno M, Fujita Y, Tanaka T, Nakamura Y, Kikuta J, Ishii M . Layer V cortical neurons require microglial support for survival during postnatal development. Nat Neurosci. 2013; 16(5):543-51. DOI: 10.1038/nn.3358. View

Varol D, Mildner A, Blank T, Shemer A, Barashi N, Yona S . Dicer Deficiency Differentially Impacts Microglia of the Developing and Adult Brain. Immunity. 2017; 46(6):1030-1044.e8. DOI: 10.1016/j.immuni.2017.05.003. View

Strosznajder A, Wojtowicz S, Jezyna M, Sun G, Strosznajder J . Recent Insights on the Role of PPAR-β/δ in Neuroinflammation and Neurodegeneration, and Its Potential Target for Therapy. Neuromolecular Med. 2020; 23(1):86-98. PMC: 7929960. DOI: 10.1007/s12017-020-08629-9. View

Michailidou I, Willems J, Kooi E, van Eden C, Gold S, Geurts J . Complement C1q-C3-associated synaptic changes in multiple sclerosis hippocampus. Ann Neurol. 2015; 77(6):1007-26. DOI: 10.1002/ana.24398. View

Casciati A, Dobos K, Antonelli F, Benedek A, Kempf S, Belles M . Age-related effects of X-ray irradiation on mouse hippocampus. Oncotarget. 2016; 7(19):28040-58. PMC: 5053708. DOI: 10.18632/oncotarget.8575. View

Ali F, Arevalo O, Zorofchian S, Patrizz A, Riascos R, Tandon N . Cerebral Radiation Necrosis: Incidence, Pathogenesis, Diagnostic Challenges, and Future Opportunities. Curr Oncol Rep. 2019; 21(8):66. DOI: 10.1007/s11912-019-0818-y. View

Kang E, Hwang J, Lee W, Lee G, Choi M, Paek K . Ligand-activated PPARδ inhibits angiotensin II-stimulated hypertrophy of vascular smooth muscle cells by targeting ROS. PLoS One. 2019; 14(1):e0210482. PMC: 6324793. DOI: 10.1371/journal.pone.0210482. View

Li Q, Cheng Z, Zhou L, Darmanis S, Neff N, Okamoto J . Developmental Heterogeneity of Microglia and Brain Myeloid Cells Revealed by Deep Single-Cell RNA Sequencing. Neuron. 2019; 101(2):207-223.e10. PMC: 6336504. DOI: 10.1016/j.neuron.2018.12.006. View

10.

Pannasch U, Farber K, Nolte C, Blonski M, Chiu S, Messing A . The potassium channels Kv1.5 and Kv1.3 modulate distinct functions of microglia. Mol Cell Neurosci. 2006; 33(4):401-11. DOI: 10.1016/j.mcn.2006.08.009. View

11.

Vukovic J, Colditz M, Blackmore D, Ruitenberg M, Bartlett P . Microglia modulate hippocampal neural precursor activity in response to exercise and aging. J Neurosci. 2012; 32(19):6435-43. PMC: 6621117. DOI: 10.1523/JNEUROSCI.5925-11.2012. View

12.

Ramanan S, Kooshki M, Zhao W, Hsu F, Riddle D, Robbins M . The PPARalpha agonist fenofibrate preserves hippocampal neurogenesis and inhibits microglial activation after whole-brain irradiation. Int J Radiat Oncol Biol Phys. 2009; 75(3):870-7. PMC: 2789462. DOI: 10.1016/j.ijrobp.2009.06.059. View

13.

Li W, Zhang Z, Zhang K, Xue Z, Li Y, Zhang Z . Arctigenin Suppress Th17 Cells and Ameliorates Experimental Autoimmune Encephalomyelitis Through AMPK and PPAR-γ/ROR-γt Signaling. Mol Neurobiol. 2015; 53(8):5356-66. DOI: 10.1007/s12035-015-9462-1. View

14.

Schnegg C, Kooshki M, Hsu F, Sui G, Robbins M . PPARδ prevents radiation-induced proinflammatory responses in microglia via transrepression of NF-κB and inhibition of the PKCα/MEK1/2/ERK1/2/AP-1 pathway. Free Radic Biol Med. 2012; 52(9):1734-43. PMC: 3341532. DOI: 10.1016/j.freeradbiomed.2012.02.032. View

15.

Reed S, Escayg A . Extracellular vesicles in the treatment of neurological disorders. Neurobiol Dis. 2021; 157:105445. PMC: 8817677. DOI: 10.1016/j.nbd.2021.105445. View

16.

Yuan H, Gaber M, Boyd K, Wilson C, Kiani M, Merchant T . Effects of fractionated radiation on the brain vasculature in a murine model: blood-brain barrier permeability, astrocyte proliferation, and ultrastructural changes. Int J Radiat Oncol Biol Phys. 2006; 66(3):860-6. DOI: 10.1016/j.ijrobp.2006.06.043. View

17.

Chang E, Wefel J, Hess K, Allen P, Lang F, Kornguth D . Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009; 10(11):1037-44. DOI: 10.1016/S1470-2045(09)70263-3. View

18.

Zhang F, Qian L, Flood P, Shi J, Hong J, Gao H . Inhibition of IkappaB kinase-beta protects dopamine neurons against lipopolysaccharide-induced neurotoxicity. J Pharmacol Exp Ther. 2010; 333(3):822-33. PMC: 2879929. DOI: 10.1124/jpet.110.165829. View

19.

Meucci O, Fatatis A, Simen A, Miller R . Expression of CX3CR1 chemokine receptors on neurons and their role in neuronal survival. Proc Natl Acad Sci U S A. 2000; 97(14):8075-80. PMC: 16672. DOI: 10.1073/pnas.090017497. View

20.

Zhang F, Zhang Y, Lv X, Xu B, Zhang H, Yan J . Evolution of an X-Linked miRNA Family Predominantly Expressed in Mammalian Male Germ Cells. Mol Biol Evol. 2019; 36(4):663-678. PMC: 6445303. DOI: 10.1093/molbev/msz001. View