PMID- 18239176 OWN - NLM STAT- MEDLINE DCOM- 20080331 LR - 20161122 IS - 1524-4628 (Electronic) IS - 0039-2499 (Linking) VI - 39 IP - 3 DP - 2008 Mar TI - Brain-derived neurotrophic factor but not forced arm use improves long-term outcome after photothrombotic stroke and transiently upregulates binding densities of excitatory glutamate receptors in the rat brain. PG - 1012-21 LID - 10.1161/STROKEAHA.107.495069 [doi] AB - BACKGROUND AND PURPOSE: Both application of neurotrophic factors like brain-derived neurotrophic factor (BDNF) and constraint-induced movement therapy like forced arm use have been shown to potentially improve outcome after stroke. The aim of the present study was to check whether postischemic long-term outcome correlates to specific modifications in the abundance of various neurotransmitter receptors. METHODS: Adult male Wistar rats were subjected to photothrombotic ischemia and assigned to various treatment groups (n=5 each) with end points at 3 and 6 weeks: (1) ischemic control (saline); (2) BDNF (ischemia, 20 microg BDNF); (3) forced arm use (ischemia, saline, and ipsilateral plaster cast for 5 or 14 days for the 3- and 6-week groups, respectively); and (4) combined treatment (combi; ischemia, 20 microg BDNF, forced arm use). Animals received intravenous bolus infusions of saline or BDNF 1 hour 3 and 5 days after ischemia, respectively. A group of sham rats (n=2) served as a control. A battery of behavioral tests was performed before and up to 6 weeks after ischemia. Quantitative in vitro receptor autoradiography was performed on 12-microm-thick cryostat sections using [(3)H]MK-801, [(3)H]AMPA, and [(3)H]muscimol for labeling of NMDA, AMPA, and GABA(A) receptors, respectively. RESULTS: Best functional outcome was seen after BDNF treatment, whereas vice versa rats with forced arm use did worse in behavioral performance. Improved behavioral outcome was associated with increased perilesional binding densities of NMDA and AMPA receptors 3 weeks after stroke. CONCLUSIONS: Our findings suggest that transient enhanced neurotransmission as reflected by increased ligand binding of NMDA and AMPA receptors may participate in successful postlesional reorganization processes. FAU - Muller, Harald D AU - Muller HD AD - Department of Neuropathology, Johannes Gutenberg-University of Mainz, Mainz, Germany. FAU - Hanumanthiah, Kiran M AU - Hanumanthiah KM FAU - Diederich, Kai AU - Diederich K FAU - Schwab, Stefan AU - Schwab S FAU - Schabitz, Wolf-Rudiger AU - Schabitz WR FAU - Sommer, Clemens AU - Sommer C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080131 PL - United States TA - Stroke JT - Stroke JID - 0235266 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Excitatory Amino Acid Antagonists) RN - 0 (GABA Agonists) RN - 0 (Ligands) RN - 0 (Receptors, Glutamate) RN - 2763-96-4 (Muscimol) RN - 6LR8C1B66Q (Dizocilpine Maleate) RN - 77521-29-0 (alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid) SB - IM MH - Animals MH - Autoradiography MH - Brain/*metabolism/pathology MH - Brain-Derived Neurotrophic Factor/*therapeutic use MH - Cerebral Infarction/etiology/pathology MH - Dizocilpine Maleate/metabolism MH - Excitatory Amino Acid Antagonists/metabolism MH - *Forelimb MH - GABA Agonists/metabolism MH - Intracranial Thrombosis/complications MH - Ligands MH - Male MH - Motor Activity/drug effects MH - Muscimol/metabolism MH - *Physical Therapy Modalities MH - Rats MH - Rats, Wistar MH - Receptors, Glutamate/*metabolism MH - Restraint, Physical MH - Stroke/etiology/physiopathology/*therapy MH - Up-Regulation MH - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/metabolism EDAT- 2008/02/02 09:00 MHDA- 2008/04/01 09:00 CRDT- 2008/02/02 09:00 PHST- 2008/02/02 09:00 [pubmed] PHST- 2008/04/01 09:00 [medline] PHST- 2008/02/02 09:00 [entrez] AID - STROKEAHA.107.495069 [pii] AID - 10.1161/STROKEAHA.107.495069 [doi] PST - ppublish SO - Stroke. 2008 Mar;39(3):1012-21. doi: 10.1161/STROKEAHA.107.495069. Epub 2008 Jan 31.