The missing link: TNF-α as a unifying mechanism in methamphetamine-induced neuronal dysfunction and blood-brain barrier compromise

Methamphetamine use disorder remains a significant public health concern, impacting neuronal function, immune responses, and vascular integrity. Of particular interest is methamphetamine's disruption of the blood–brain barrier (BBB), a key event that triggers neuroimmune dysfunction and the development of neurodegenerative conditions. While the systemic effects of methamphetamine are well-characterized, the mechanism(s) governing its dysregulation of BBB physiology remain poorly understood. Emerging evidence suggests that the methamphetamine-induced production of tumor necrosis factor (TNF), occurring both in the periphery and within the central nervous system, triggers a cascade of molecular events that compromises BBB permeability. This review provides a comprehensive overview of current findings on the cross interaction between methamphetamine and the BBB, with particular emphasis on the potential role of TNF in dysregulation of BBB permeability and dysfunction. By elucidating the complex interplay between methamphetamine, TNF, and the BBB, we aim to inform the development of targeted interventions and preventative strategies to mitigate methamphetamine-induced neurovascular and neuroimmune dysfunction.