Microglial Metabolism After Pediatric Traumatic Brain Injury - Overlooked Bystanders or Active Participants?

Overview

Journal Front Neurol

Specialty Neurology

Date 2021 Feb 11

PMID 33569038

Citations 3

Authors

Aria C Shi

Ursula Rohlwink

Susanna Scafidi

Sujatha Kannan

Affiliations

Soon will be listed here.

Abstract

Microglia play an integral role in brain development but are also crucial for repair and recovery after traumatic brain injury (TBI). TBI induces an intense innate immune response in the immature, developing brain that is associated with acute and chronic changes in microglial function. These changes contribute to long-lasting consequences on development, neurologic function, and behavior. Although alterations in glucose metabolism are well-described after TBI, the bulk of the data is focused on metabolic alterations in astrocytes and neurons. To date, the interplay between alterations in intracellular metabolic pathways in microglia and the innate immune response in the brain following an injury is not well-studied. In this review, we broadly discuss the microglial responses after TBI. In addition, we highlight reported metabolic alterations in microglia and macrophages, and provide perspective on how changes in glucose, fatty acid, and amino acid metabolism can influence and modulate the microglial phenotype and response to injury.

Citing Articles

The mechanism of microglia-mediated immune inflammation in ischemic stroke and the role of natural botanical components in regulating microglia: A review.

Zeng J, Bao T, Yang K, Zhu X, Wang S, Xiang W Front Immunol. 2023; 13:1047550.

PMID: 36818470 PMC: 9933144. DOI: 10.3389/fimmu.2022.1047550.

Establishment and Application of a Novel Model of Microglial Activation in Traumatic Brain Injury.

Liu N, Li Y, Jiang Y, Shi S, Niamnud A, Vodovoz S J Neurosci. 2022; 43(2):319-332.

PMID: 36446585 PMC: 9838700. DOI: 10.1523/JNEUROSCI.1539-22.2022.

Significance of Microglial Energy Metabolism in Maintaining Brain Homeostasis.

Bielanin J, Sun D Transl Stroke Res. 2022; 14(4):435-437.

PMID: 35879639 PMC: 9877240. DOI: 10.1007/s12975-022-01069-6.

References

Infantino V, Iacobazzi V, Palmieri F, Menga A . ATP-citrate lyase is essential for macrophage inflammatory response. Biochem Biophys Res Commun. 2013; 440(1):105-11. DOI: 10.1016/j.bbrc.2013.09.037. View

McKenna M, Scafidi S, Robertson C . Metabolic Alterations in Developing Brain After Injury: Knowns and Unknowns. Neurochem Res. 2015; 40(12):2527-43. PMC: 4961252. DOI: 10.1007/s11064-015-1600-7. View

Sinz E, Kochanek P, Heyes M, Wisniewski S, Bell M, Clark R . Quinolinic acid is increased in CSF and associated with mortality after traumatic brain injury in humans. J Cereb Blood Flow Metab. 1998; 18(6):610-5. DOI: 10.1097/00004647-199806000-00002. View

Wen J, Jones M, Tanaka M, Selvaraj P, Symes A, Cox B . WWL70 protects against chronic constriction injury-induced neuropathic pain in mice by cannabinoid receptor-independent mechanisms. J Neuroinflammation. 2018; 15(1):9. PMC: 5759843. DOI: 10.1186/s12974-017-1045-9. View

Kumar A, Loane D . Neuroinflammation after traumatic brain injury: opportunities for therapeutic intervention. Brain Behav Immun. 2012; 26(8):1191-201. DOI: 10.1016/j.bbi.2012.06.008. View

Matcovitch-Natan O, Winter D, Giladi A, Aguilar S, Spinrad A, Sarrazin S . Microglia development follows a stepwise program to regulate brain homeostasis. Science. 2016; 353(6301):aad8670. DOI: 10.1126/science.aad8670. View

Li X, Melief E, Postupna N, Montine K, Keene C, Montine T . Prostaglandin E2 receptor subtype 2 regulation of scavenger receptor CD36 modulates microglial Aβ42 phagocytosis. Am J Pathol. 2014; 185(1):230-9. PMC: 4278245. DOI: 10.1016/j.ajpath.2014.09.016. View

Kaindl A, Zabel C, Stefovska V, Lehnert R, Sifringer M, Klose J . Subacute proteome changes following traumatic injury of the developing brain: Implications for a dysregulation of neuronal migration and neurite arborization. Proteomics Clin Appl. 2010; 1(7):640-9. DOI: 10.1002/prca.200600696. View

Frisca F, Sabbadini R, Goldshmit Y, Pebay A . Biological effects of lysophosphatidic acid in the nervous system. Int Rev Cell Mol Biol. 2012; 296:273-322. DOI: 10.1016/B978-0-12-394307-1.00005-9. View

10.

Schwab J, Beschorner R, Meyermann R, Gozalan F, Schluesener H . Persistent accumulation of cyclooxygenase-1-expressing microglial cells and macrophages and transient upregulation by endothelium in human brain injury. J Neurosurg. 2002; 96(5):892-9. DOI: 10.3171/jns.2002.96.5.0892. View

11.

White C, Lee J, Choi J, Chu T, Scafidi S, Wolfgang M . Determining the Bioenergetic Capacity for Fatty Acid Oxidation in the Mammalian Nervous System. Mol Cell Biol. 2020; 40(10). PMC: 7189099. DOI: 10.1128/MCB.00037-20. View

12.

Katz P, Sulzer J, Impastato R, Teng S, Rogers E, Molina P . Endocannabinoid degradation inhibition improves neurobehavioral function, blood-brain barrier integrity, and neuroinflammation following mild traumatic brain injury. J Neurotrauma. 2014; 32(5):297-306. PMC: 4348366. DOI: 10.1089/neu.2014.3508. View

13.

Holmin S, Soderlund J, Biberfeld P, Mathiesen T . Intracerebral inflammation after human brain contusion. Neurosurgery. 1998; 42(2):291-8; discussion 298-9. DOI: 10.1097/00006123-199802000-00047. View

14.

Tchantchou F, Zhang Y . Selective inhibition of alpha/beta-hydrolase domain 6 attenuates neurodegeneration, alleviates blood brain barrier breakdown, and improves functional recovery in a mouse model of traumatic brain injury. J Neurotrauma. 2012; 30(7):565-79. PMC: 3636589. DOI: 10.1089/neu.2012.2647. View

15.

Guerriero R, Giza C, Rotenberg A . Glutamate and GABA imbalance following traumatic brain injury. Curr Neurol Neurosci Rep. 2015; 15(5):27. PMC: 4640931. DOI: 10.1007/s11910-015-0545-1. View

16.

Wu Y, Dissing-Olesen L, MacVicar B, Stevens B . Microglia: Dynamic Mediators of Synapse Development and Plasticity. Trends Immunol. 2015; 36(10):605-613. PMC: 4841266. DOI: 10.1016/j.it.2015.08.008. View

17.

Bazan N . Omega-3 fatty acids, pro-inflammatory signaling and neuroprotection. Curr Opin Clin Nutr Metab Care. 2007; 10(2):136-41. DOI: 10.1097/MCO.0b013e32802b7030. View

18.

Afridi R, Lee W, Suk K . Microglia Gone Awry: Linking Immunometabolism to Neurodegeneration. Front Cell Neurosci. 2020; 14:246. PMC: 7438837. DOI: 10.3389/fncel.2020.00246. View

19.

Wallisch J, Simon D, Bayir H, Bell M, Kochanek P, Clark R . Cerebrospinal Fluid NLRP3 is Increased After Severe Traumatic Brain Injury in Infants and Children. Neurocrit Care. 2017; 27(1):44-50. PMC: 5680164. DOI: 10.1007/s12028-017-0378-7. View

20.

Im D . Functions of omega-3 fatty acids and FFA4 (GPR120) in macrophages. Eur J Pharmacol. 2015; 785:36-43. DOI: 10.1016/j.ejphar.2015.03.094. View