Altered hippocampal lipid profile underlies anxiety-like behavior secondary to mild traumatic brain injury

Traumatic brain injury (TBI) remains a major cause of neurological morbidity worldwide, and mild TBI (mTBI) is frequently associated with emotional disturbances, including anxiety-like behavior. Although classical mechanisms of secondary injury have been extensively characterized, metabolic alterations, particularly those involving cerebral lipid homeostasis, remain incompletely defined. Given the structural and regulatory roles of lipids in the central nervous system, disruption of lipid metabolism may contribute to early post-traumatic dysfunction. We hypothesized that mTBI induces region-specific alterations in brain lipid metabolism and that these changes are associated with anxiety-like behavior during the acute post-injury phase. Adult male C57BL/6 mice were subjected to a weight-drop model of mTBI and evaluated 48–72 h post-injury using different behavioral paradigms. Lipid classes were quantified in the hippocampus, prefrontal cortex, and serum by thin-layer chromatography. mTBI induced anxiety-like behavior without locomotor impairment. Biochemical analyses revealed region-dependent lipid alteration predominantly in the ipsilateral hippocampus, characterized by reduced diacylglycerol and monoacylglycerol levels alongside increased total phospholipids and specific subclasses. Correlation analyses demonstrated significant associations between anxiety-related behavioral parameters and lipid classes across tissues. These findings indicate that mild TBI is accompanied by early, region-specific lipid alterations that are associated with behavioral changes during the acute post-injury period.