Pelargonium Graveolens Essential Oil Improves Recovery after Experimental Traumatic Brain Injury

Traumatic brain injury (TBI) is a significant global health issue, causing cognitive, motor, and psychological impairments while increasing neurodegenerative disease risk. Essential oil extracted from Pelargonium graveolens ( Pg ), also known as geranium oil, is Food and Drug Administration (FDA)-approved and classified as generally recognized as safe for use in the food industry. Pg oil contains low molecular weight lipophilic compounds, which potentially traverse the blood–brain barrier and modulate brain functions. We have previously demonstrated that Pg oil exhibits anti-inflammatory and neuroprotective effects. Given the significant role of these processes in TBI pathophysiology and the absence of FDA-approved treatments, our goal in this study was to investigate the therapeutic potential of Pg oil in the closed-head injury (CHI) model for TBI. For this purpose, male C57BL/6JOlaHsd mice (8–9 weeks old, 20–25 g) underwent CHI using a modified weight-drop device and were treated orally with Pg oil for 2 weeks; 56 mice served as controls. Treatment group assignment was randomized based on neurological severity score (NSS) evaluation at 1-hour postinjury. Mice were monitored for 1 month following injury using a comprehensive behavioral battery administered in a blinded manner, then sacrificed for histopathological assessment. Pg was obtained from the Newe Ya’ar Research Center MAP Germplasm collection and prepared via steam distillation. The essential oil composition was characterized using gas chromatography–mass spectrometry (GC–MS). The therapeutic efficacy of Pg oil was demonstrated through multiple behavioral assessments, including the Barnes Maze, Y-maze, and novel object recognition test. Pg oil significantly enhanced cognitive performance in the injured mice, with effects persisting for at least 1-month post-injury. Histopathological evaluation revealed that Pg oil reduced axonal damage and increased neuronal survival in cortical and hippocampal regions. Additionally, Pg oil treatment significantly improved brain tissue preservation, as evidenced by reduced cortical and corpus callosum atrophy and decreased ventricle enlargement. The therapeutic benefits stemmed from anti-inflammatory and antioxidant activities, evidenced by reduced tumor necrosis factor-α, interleukin-1β, and lipid peroxidation levels, along with M2 phenotype immunomodulation, and elevated phosphorylated cyclic-AMP response element binding protein levels. The exclusive use of male mice in this study necessitates future investigation of Pg effects in female subjects. Our findings support the potential applications of Pg oil as a novel nutraceutical and a therapeutic candidate for TBI treatment and improvement of cognitive outcomes, warranting further translational research in TBI patients.