Glycerophospholipids (GPLs) are amphipathic lipids that contain polar phosphate groups and hydrophobic fatty acyl chains attached to a glycerol backbone (Farooqui, Horrocks et al. 2000; Montealegre, Verardo et al. 2014). They are the primary building blocks of cellular membranes, which serve as a boundary for cellular and subcellular structures and maintain their integrity (Montealegre, Verardo et al. 2014; Wang and Tontonoz 2019). They also serve as docking platforms for different receptors and play an important role in cellular signal transduction pathways (Farooqui, Horrocks et al. 2000). Any perturbation of phospholipid composition and abundance can have deleterious impact on cellular function and survival. They are vulnerable to oxidative stress and metabolic dysfunctions. Phospholipid homeostasis is disrupted in different pathological conditions including traumatic brain injury (TBI) (Farooqui, Horrocks et al. 2000; Sarkar, Jones et al. 2020).

TBI is caused by the physical impact of external forces to the brain, which can be due to falls, motor vehicle accidents, assaults, combat situations or contact sport activities (Werner and Engelhard 2007; Xiong, Mahmood et al. 2013; Gardner and Zafonte 2016). It is one of the major causes of premature death for people of all ages. Those who survive the early impact of TBI may develop lifelong disabilities. Globally around 27 million people suffer from TBI or TBI related illness annually. In the US, this number is around 1.7 million (Injury and Spinal Cord Injury 2019). The pathophysiology of TBI is highly complex. Primary mechanical injury initiates a cascade of biochemical events leading to acute and progressive neurodegeneration and neuroinflammation (Werner and Engelhard 2007; Stoica and Faden 2010, Faden, Wu et al. 2016). These biochemical events include calcium imbalance, glutamate excitotoxicity, oxidative stress, ER stress, mitochondrial and lysosomal dysfunction. (Stoica and Faden 2010; Nguyen, Fiest et al. 2016; Vemuganti and Hall 2017). Recent studies also demonstrate that many types of phospholipids are dysregulated following TBI (Abdullah, Evans et al. 2014; Anthonymuthu, Kenny et al. 2019; Sarkar, Jones et al. 2020; Thomas, Dickens et al. 2022). Such changes in phospholipids homeostasis in response to TBI have been detected in the different regions of the injured brain as well as systemically in the blood. In this review, we discuss the mechanisms and implications of glycerophospholipids dysregulations after TBI.