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Synergistic disruption of the blood-brain barrier in tree shrews by Methamphetamine and HIV-1 Tat via TRPM2-Mediated astrocyte inflammation - PubMed

4 hours ago
  • #Blood-brain barrier
  • #TRPM2
  • #Neuroinflammation
  • Methamphetamine (METH) and HIV-1 Tat protein (Tat) synergistically disrupt the blood-brain barrier (BBB) in tree shrews.
  • The disruption is mediated via TRPM2 channels in astrocytes, leading to neuroinflammation and BBB damage.
  • Both in vitro and in vivo models showed that METH and Tat decrease tight junction proteins and increase BBB permeability.
  • Pharmacological inhibition or astrocyte-specific knockdown of TRPM2 mitigated BBB damage and neuroinflammation.
  • TRPM2 inhibition also alleviated METH + Tat-induced behavioral impairments in tree shrews.
  • The study identifies TRPM2 as a potential therapeutic target for neurotoxicity caused by METH and HIV-1 Tat.