Nicotine inhalant via E‐cigarette facilitates sensorimotor function recovery by upregulating neuronal BDNF–TrkB signalling in traumatic brain injury

Abstract Background and Purpose Traumatic brain injury (TBI) causes lifelong physical and psychological dysfunction in affected individuals. The current study investigated the effects of chronic nicotine exposure via E‐cigarettes (E‐cig) (vaping) on TBI‐associated behavioural and biochemical changes. Experimental Approach Adult C57/BL6J male mice were subjected to controlled cortical impact (CCI) followed by daily exposure to E‐cig vapour for 6 weeks. Sensorimotor functions, locomotion, and sociability were subsequently evaluated by nesting, open field, and social approach tests, respectively. Immunoblots were conducted to examine the expression of mature brain‐derived neurotrophic factor (mBDNF) and associated downstream proteins (p‐Erk, p‐Akt). Histological analyses were performed to evaluate neuronal survival and neuroinflammation. Key Results Post‐injury chronic nicotine exposure significantly improved nesting performance in CCI mice. Histological analysis revealed increased survival of cortical neurons in the perilesion cortex with chronic nicotine exposure. Immunoblots revealed that chronic nicotine exposure significantly up‐regulated mBDNF, p‐Erk and p‐Akt expression in the perilesion cortex of CCI mice. Immunofluorescence microscopy indicated that elevated mBDNF and p‐Akt expression were mainly localized within cortical neurons. Immunolabelling of Iba1 demonstrated that chronic nicotine exposure attenuated microglia‐mediated neuroinflammation. Conclusions and Implications Post‐injury chronic nicotine exposure via vaping facilitates recovery of sensorimotor function by upregulating neuroprotective mBDNF/TrkB/Akt/Erk signalling. These findings suggest potential neuroprotective properties of nicotine despite its highly addictive nature. Thus, understanding the multifaceted effects of chronic nicotine exposure on TBI‐associated symptoms is crucial for paving the way for informed and properly managed therapeutic interventions.