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Tissue plasminogen activator is required for striatal post-ischemic synaptic potentiation
Diego Centonze1, Emilia Saulle, Antonio Pisani
1Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy.
Neuroreport
|April 2, 2002
Summary
Tissue plasminogen activator (tPA) contributes to excitotoxicity after stroke. Preventing tPA activity protected against NMDA-dependent synaptic potentiation, suggesting a neuroprotective role for tPA inhibition.
Area of Science:
- Neuroscience
- Molecular Biology
- Cerebrovascular Research
Background:
- Tissue plasminogen activator (tPA) is implicated in neuronal damage following cerebral ischemia and excitotoxicity.
- The precise mechanism by which tPA promotes ischemia-induced neuronal damage remains unclear.
Purpose of the Study:
- To investigate the role of tPA in ischemia-induced neuronal damage and synaptic potentiation.
- To clarify how tPA influences excitotoxicity in the context of cerebral ischemia.
Main Methods:
- In vitro electrophysiological experiments were conducted using striatal slices from mice genetically engineered to lack tPA.
- Neurons were exposed to combined oxygen and glucose deprivation to simulate ischemic conditions.
Main Results:
- tPA deficiency did not alter membrane depolarization in striatal neurons during oxygen and glucose deprivation.
- Ablation of tPA completely prevented the induction of NMDA-dependent post-ischemic long-term potentiation.
- The absence of post-ischemic potentiation in tPA-lacking mice correlated with significant neuroprotection after middle cerebral artery occlusion.
Conclusions:
- tPA is crucial for the development of NMDA-dependent synaptic potentiation following ischemic events.
- Inhibiting tPA confers neuroprotection against ischemic brain injury, likely by preventing excitotoxic synaptic changes.