Different postischemic protein expression of the GABA(A) receptor alpha2 subunit and the plasticity-associated protein MAP1B after treatment with BDNF versus G-CSF in the rat brain.
OBJECTIVE
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 alpha2 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 alpha2 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.
Müller
Harald D
HD
Division of Neuropathology, Bezirkskrankenhaus Günzburg, Günzburg, Germany.
Neder
Angelika
A
Sommer
Clemens
C
Schäbitz
Wolf-Rüdiger
WR
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D020767:Intracranial Thrombosis / Q000150:complications; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D020521:Stroke / Q000188:drug therapy / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D016708:Synaptophysin / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; C520011:Gabra2 protein, rat; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D011963:Receptors, GABA-A; D016708:Synaptophysin; C085284:microtubule-associated protein 1B; D016179:Granulocyte Colony-Stimulating Factor