Einfluss der Wachstumsfaktoren BDNF und G-CSF auf die Neurotransmitter-Rezeptor-Regulation und die Proteinexpression Plastizitäts-assoziierter Markerproteine nach experimenteller zerebraler Ischämie
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Purpose: Recent data indicate that both brain-derived neurotrophic factor (BDNF) and granulocyte-colony stimulating factor (G-CSF) exert substantial neuroregenerative effects and improve functional outcome after ischemic stroke. In the present study, we checked for potential differences in the postischemic modulation of various excitatory and inhibitory neurotransmitter receptors as well as various marker molecules for structural plasticity by BDNF versus G-CSF. Methods: Adult male Wistar rats were subjected to photothrombotic ischemia and subsequently treated with NaCl, BDNF or G-CSF, respectively. After 6 weeks, postischemic protein expression of the NR1, GluR1 and a2 subunit of the NMDA, AMPA and GABA_A receptor, respectively, was semiquantitatively determined ipsi- and contralateral to the ischemic lesion. Structural plasticity was further analyzed immunohistochemically using antibodies against MAP1B, MAP2 and synaptophysin. Results: Only BNDF caused a significantly reduced postischemic protein expression of the GABA_A receptor a2 subunit and the NR1 subunit of the NMDA receptor in the hippocampus. Furthermore, BDNF compared to G-CSF increased MAP1B protein expression in the periischemic regenerative region. Conclusions: Although both BDNF and G-CSF have been shown to improve postischemic functional outcome to a similar extent, exogenous administration results in different underlying structural reorganization processes suggesting specific modulations of plasticity-associated events by these trophic factors.
Subject HeadingsBrain-derived neurotrophic factor [MeSH]
Granulocyte colony-stimulating factor [MeSH]
Intercellular signaling peptides and proteins [MeSH]
Neuronal plasticity [MeSH]
Receptors, neurotransmitter [MeSH]