Propofol treatment modulates neurite extension regulated by immunologically challenged rat primary astrocytes: a possible role of PAI-1

다국어 초록 (Multilingual Abstract)

Propofol, a widely used anesthetic, regulatesneurological processes including neurotoxicity, neuroprotection,glial activation, synaptic plasticity and neuronalmaturation. Tissue plasminogen activator/tissue plasminogenactivator inhibitor-1 (tPA/PAI-1) in CNS acts as aneuromodulator regulating synaptic plasticity, neuriteoutgrowth, seizure spreading and cell survival. Here, weinvestigated the effects of propofol on tPA/PAI-1 systemusing cultured neurons and astrocytes and their role in theregulation of neurite extension. Cultured rat primaryastrocytes were treated with propofol (1–10 lM) and LPS(10 ng/ml). The expression of functional tPA/PAI-1 wasexamined by casein zymography, Western blot and RTPCR.
Alternatively, culture supernatants were added tocultured rat primary neuron to investigate the effects onneurite extension. Propofol alone did not affect tPA activityin rat primary cortical neuron. Similarly, propofol alonechanged neither tPA nor PAI-1 activity in rat primaryastrocytes. In immunologically challenged situation usingLPS, propofol synergistically increased expression of PAI-1 in rat primary astrocytes without affecting tPA expressionin a manner dependent on MAPKs activation. Increased expression of PAI-1 reduced tPA activity in LPSplus propofol-treated rat primary astrocytes. Consistentwith the critical role of tPA activity in the regulation ofneurite extension (Cho et al. 2013), the diminished tPAactivity in astrocyte culture supernatants resulted indecreased neurite extension when administered to culturedrat primary cortical neuron. The results from the presentstudy suggest that propofol, especially in immunologicallychallengedsituation, dysregulates tPA/PAI-1 system inbrain. Whether the dysregulated tPA/PAI-1 activityadversely affects neural differentiation as well as regenerationof neuron in vivo should be empirically determined inthe future.

참고문헌 (Reference)

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