Key role of tissue plasminogen activator in neurovascular coupling Academic Article uri icon


MeSH Major

  • Neurons
  • Tissue Plasminogen Activator


  • The increase in blood flow evoked by synaptic activity is essential for normal brain function and underlies functional brain imaging signals. Nitric oxide, a vasodilator released by NMDA receptor activation, is critical for the flow increase, but the factors linking NMDA receptor activity to nitric oxide-dependent hyperemia are poorly understood. Here, we show that tissue plasminogen activator (tPA), a serine protease implicated in NMDA receptor signaling, is required for the flow increase evoked by somatosensory stimulation. tPA acts by facilitating neuronal nitric oxide release, but this effect does not involve enhancement of NMDA currents or the associated intracellular Ca(2+) rise. Rather, the evidence suggests that tPA controls NMDA-dependent nitric oxide synthesis by influencing the phosphorylation state of neuronal nitric oxide synthase. These findings unveil a previously unrecognized role of tPA in vital homeostatic mechanisms coupling NMDA receptor signaling with nitric oxide synthesis and local cerebral perfusion.

publication date

  • January 22, 2008



  • Academic Article



  • eng

PubMed Central ID

  • PMC2242693

Digital Object Identifier (DOI)

  • 10.1073/pnas.0708823105

PubMed ID

  • 18195371

Additional Document Info

start page

  • 1073

end page

  • 8


  • 105


  • 3