Antimicrobial Peptides and Complement in Neonatal Hypoxia-ischemia Induced Brain Damage

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2015 Mar 3

PMID 25729383

Citations 43

Authors

Eridan Rocha-Ferreira

Mariya Hristova

Affiliations

Soon will be listed here.

Abstract

Hypoxic-ischemic encephalopathy (HIE) is a clinical condition in the neonate, resulting from oxygen deprivation around the time of birth. HIE affects 1-5/1000 live births worldwide and is associated with the development of neurological deficits, including cerebral palsy, epilepsy, and cognitive disabilities. Even though the brain is considered as an immune-privileged site, it has innate and adaptive immune response and can produce complement (C) components and antimicrobial peptides (AMPs). Dysregulation of cerebral expression of AMPs and C can exacerbate or ameliorate the inflammatory response within the brain. Brain ischemia triggers a prolonged inflammatory response affecting the progression of injury and secondary energy failure and involves both innate and adaptive immune systems, including immune-competent and non-competent cells. Following injury to the central nervous system (CNS), including neonatal hypoxia-ischemia (HI), resident microglia, and astroglia are the main cells providing immune defense to the brain in a stimulus-dependent manner. They can express and secrete pro-inflammatory cytokines and therefore trigger prolonged inflammation, resulting in neurodegeneration. Microglial cells express and release a wide range of inflammation-associated molecules including several components of the complement system. Complement activation following neonatal HI injury has been reported to contribute to neurodegeneration. Astrocytes can significantly affect the immune response of the CNS under pathological conditions through production and release of pro-inflammatory cytokines and immunomodulatory AMPs. Astrocytes express β-defensins, which can chemoattract and promote maturation of dendritic cells (DC), and can also limit inflammation by controlling the viability of these same DC. This review will focus on the balance of complement components and AMPs within the CNS following neonatal HI injury and the effect of that balance on the subsequent brain damage.

Citing Articles

Inter-alpha Inhibitor Proteins Modulate Microvascular Endothelial Components and Cytokines After Exposure to Hypoxia-Ischemia in Neonatal Rats.

Koehn L, Nguyen K, Tucker R, Lim Y, Chen X, Stonestreet B Mol Neurobiol. 2024; 62(4):5057-5072.

PMID: 39505805 DOI: 10.1007/s12035-024-04594-7.

Identification and analysis of oxidative stress-related genes in hypoxic-ischemic brain damage using bioinformatics and experimental verification.

Jin N, Sha S, Ruan Y, Ouyang Y Immun Inflamm Dis. 2024; 12(8):e70000.

PMID: 39172048 PMC: 11340634. DOI: 10.1002/iid3.70000.

NKG2D knockdown improves hypoxic-ischemic brain damage by inhibiting neuroinflammation in neonatal mice.

Liu L, Yang Y, Wu T, Du J, Long F Sci Rep. 2024; 14(1):2326.

PMID: 38282118 PMC: 10822867. DOI: 10.1038/s41598-024-52780-3.

Knockdown of interleukin-6 plays a neuroprotective role against hypoxia-ischemia in neonatal rats via inhibition of caspase 3 and Bcl-2-associated X protein signaling pathway.

Yang X, Liao K, Deng I, Zhang L Ibrain. 2023; 8(3):413-428.

PMID: 37786746 PMC: 10529178. DOI: 10.1002/ibra.12067.

Periventricular Microglia Polarization and Morphological Changes Accompany NLRP3 Inflammasome-Mediated Neuroinflammation after Hypoxic-Ischemic White Matter Damage in Premature Rats.

Yang L, Zhang Y, Yu X, Li D, Liu N, Xue X J Immunol Res. 2023; 2023:5149306.

PMID: 37636861 PMC: 10460280. DOI: 10.1155/2023/5149306.

References

Doni A, Peri G, Chieppa M, Allavena P, Pasqualini F, Vago L . Production of the soluble pattern recognition receptor PTX3 by myeloid, but not plasmacytoid, dendritic cells. Eur J Immunol. 2003; 33(10):2886-93. DOI: 10.1002/eji.200324390. View

Vincent V, Tilders F, van Dam A . Inhibition of endotoxin-induced nitric oxide synthase production in microglial cells by the presence of astroglial cells: a role for transforming growth factor beta. Glia. 1997; 19(3):190-8. DOI: 10.1002/(sici)1098-1136(199703)19:3<190::aid-glia2>3.0.co;2-3. View

Trouw L, Blom A, Gasque P . Role of complement and complement regulators in the removal of apoptotic cells. Mol Immunol. 2007; 45(5):1199-207. DOI: 10.1016/j.molimm.2007.09.008. View

Aly H, Khashaba M, El-Ayouty M, El-Sayed O, Hasanein B . IL-1beta, IL-6 and TNF-alpha and outcomes of neonatal hypoxic ischemic encephalopathy. Brain Dev. 2005; 28(3):178-82. DOI: 10.1016/j.braindev.2005.06.006. View

Bax M, Goldstein M, Rosenbaum P, Leviton A, Paneth N, Dan B . Proposed definition and classification of cerebral palsy, April 2005. Dev Med Child Neurol. 2005; 47(8):571-6. DOI: 10.1017/s001216220500112x. View

Okroj M, Heinegard D, Holmdahl R, Blom A . Rheumatoid arthritis and the complement system. Ann Med. 2007; 39(7):517-30. DOI: 10.1080/07853890701477546. View

Okinaga S, Slattery D, Humbles A, Zsengeller Z, Morteau O, Kinrade M . C5L2, a nonsignaling C5A binding protein. Biochemistry. 2003; 42(31):9406-15. DOI: 10.1021/bi034489v. View

Fonseca M, Chu S, Berci A, Benoit M, Peters D, Kimura Y . Contribution of complement activation pathways to neuropathology differs among mouse models of Alzheimer's disease. J Neuroinflammation. 2011; 8(1):4. PMC: 3033336. DOI: 10.1186/1742-2094-8-4. View

Gavrilyuk V, Kalinin S, Hilbush B, Middlecamp A, McGuire S, Pelligrino D . Identification of complement 5a-like receptor (C5L2) from astrocytes: characterization of anti-inflammatory properties. J Neurochem. 2005; 92(5):1140-9. DOI: 10.1111/j.1471-4159.2004.02942.x. View

10.

Lew S, Gross C, Bednar M, Russell S, Fuller S, Ellenberger C . Complement depletion does not reduce brain injury in a rabbit model of thromboembolic stroke. Brain Res Bull. 1999; 48(3):325-31. DOI: 10.1016/s0361-9230(99)00004-0. View

11.

Schutte B, Mitros J, Bartlett J, Walters J, Jia H, Welsh M . Discovery of five conserved beta -defensin gene clusters using a computational search strategy. Proc Natl Acad Sci U S A. 2002; 99(4):2129-33. PMC: 122330. DOI: 10.1073/pnas.042692699. View

12.

Van Cauwenberghe C, Bettens K, Engelborghs S, Vandenbulcke M, Van Dongen J, Vermeulen S . Complement receptor 1 coding variant p.Ser1610Thr in Alzheimer's disease and related endophenotypes. Neurobiol Aging. 2013; 34(9):2235.e1-6. DOI: 10.1016/j.neurobiolaging.2013.03.008. View

13.

Zanjani H, Finch C, Kemper C, Atkinson J, McKeel D, Morris J . Complement activation in very early Alzheimer disease. Alzheimer Dis Assoc Disord. 2005; 19(2):55-66. DOI: 10.1097/01.wad.0000165506.60370.94. View

14.

Gimsa U, Mitchison N, Brunner-Weinzierl M . Immune privilege as an intrinsic CNS property: astrocytes protect the CNS against T-cell-mediated neuroinflammation. Mediators Inflamm. 2013; 2013:320519. PMC: 3760105. DOI: 10.1155/2013/320519. View

15.

Fraser D, Pisalyaput K, Tenner A . C1q enhances microglial clearance of apoptotic neurons and neuronal blebs, and modulates subsequent inflammatory cytokine production. J Neurochem. 2009; 112(3):733-43. PMC: 2809134. DOI: 10.1111/j.1471-4159.2009.06494.x. View

16.

Bona E, Andersson A, Blomgren K, Gilland E, Gustafson K, Hagberg H . Chemokine and inflammatory cell response to hypoxia-ischemia in immature rats. Pediatr Res. 1999; 45(4 Pt 1):500-9. DOI: 10.1203/00006450-199904010-00008. View

17.

Nijnik A, Madera L, Ma S, Waldbrook M, Elliott M, Easton D . Synthetic cationic peptide IDR-1002 provides protection against bacterial infections through chemokine induction and enhanced leukocyte recruitment. J Immunol. 2010; 184(5):2539-50. DOI: 10.4049/jimmunol.0901813. View

18.

Volpe J . Neurobiology of periventricular leukomalacia in the premature infant. Pediatr Res. 2001; 50(5):553-62. DOI: 10.1203/00006450-200111000-00003. View

19.

Bowman C, Rasley A, Tranguch S, Marriott I . Cultured astrocytes express toll-like receptors for bacterial products. Glia. 2003; 43(3):281-91. DOI: 10.1002/glia.10256. View

20.

Benjelloun N, Renolleau S, Represa A, Ben-Ari Y, Charriaut-Marlangue C . Inflammatory responses in the cerebral cortex after ischemia in the P7 neonatal Rat. Stroke. 1999; 30(9):1916-23; discussion 1923-4. DOI: 10.1161/01.str.30.9.1916. View