Exogenous brain-derived neurotrophic factor prevents postischemic downregulation of [3H]muscimol binding to GABA(A) receptors in the cortical penumbra.

Abstract

We have previously shown that exogenous application of brain-derived neurotrophic factor (BDNF) reduces infarct volume in the cortical ischemic penumbra after experimental focal ischemia [Stroke 31 (2000) 2212-2217]. Since BDNF is known to modulate the expression and function of various neurotransmitter receptors, we addressed the question whether BDNF may act via modification of postischemic ligand binding to excitatory NMDA and AMPA and/or inhibitory GABA(A) receptors, respectively. Transient focal cerebral ischemia was induced in male Wistar rats for 2 h using the suture occlusion technique. A period of 30 min after occlusion of the middle cerebral artery, BDNF (300 microg/kg per hour in vehicle; n=5) or vehicle alone (n=5) was continuously infused intravenously for 3 h. Using quantitative receptor autoradiography, postischemic ligand binding of [(3)H]MK-801, [(3)H]AMPA and [(3)H]muscimol was analyzed in the ischemic core, the ischemic cortical penumbra and corresponding regions of the contralateral hemisphere. Transient focal ischemia caused a significant reduction of [(3)H]muscimol binding to GABA(A) receptors within the ischemic cortical penumbra of placebo-treated rats. This was largely prevented by exogenous application of BDNF. [(3)H]MK-801 and [(3)H]AMPA binding values were also reduced in the cortical penumbra and the corresponding area of the contralateral hemisphere. Our data suggest that the neuroprotective effect of BDNF against ischemic damage in the cortical penumbra may be mediated in part by maintained activity of the inhibitory GABAergic system which likely counteracts glutamate induced excitotoxicity.

• Authors: Clemens Sommer, Rainer Kollmar, Stefan Schwab, Marika Kiessling, Wolf Rüdiger Schäbitz
• Journal: Brain research. Molecular brain research (Brain Res Mol Brain Res) Vol. 111 Issue 1-2 Pg. 24-30 (Mar 17 2003) ISSN: 0169-328X [Print] Netherlands
• PMID: 12654502 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Brain-Derived Neurotrophic Factor
• Excitatory Amino Acid Agonists
• Excitatory Amino Acid Antagonists
• GABA Agonists
• Neuroprotective Agents
• Receptors, GABA-A
• Receptors, N-Methyl-D-Aspartate
• Tritium
• Muscimol
• Dizocilpine Maleate
• alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid

Topics

• Animals
• Binding, Competitive (drug effects, physiology)
• Brain Ischemia (drug therapy, metabolism, physiopathology)
• Brain-Derived Neurotrophic Factor (metabolism, pharmacology)
• Cerebral Cortex (drug effects, metabolism, physiopathology)
• Cerebral Infarction (drug therapy, metabolism, physiopathology)
• Dizocilpine Maleate (pharmacology)
• Down-Regulation (drug effects, physiology)
• Excitatory Amino Acid Agonists (pharmacology)
• Excitatory Amino Acid Antagonists (pharmacology)
• GABA Agonists (pharmacology)
• Male
• Muscimol (pharmacology)
• Neurons (drug effects, metabolism)
• Neuroprotective Agents (metabolism, pharmacology)
• Rats
• Rats, Wistar
• Receptors, GABA-A (drug effects, metabolism)
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors, metabolism)
• Tritium
• alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (pharmacology)