Estrogen attenuates neuronal excitability in the insular cortex following middle cerebral artery occlusion.
The current investigation examined the role of estrogen in the insular cortex (IC) under both normal and ischemic conditions. Experiments were done in anaesthetized male Sprague-Dawley rats. The effect of systemic 17beta-estradiol (estrogen) administration on levels of amino acids and of endogenous estrogen obtained by microdialysis and its effect on neuronal activity of cells located in the insular cortex were measured in the absence of, and following permanent occlusion of, the right middle cerebral artery (MCA). In normal rats, intravenous (i.v.) injection of estrogen resulted in a significant increase (greater than 25 spikes/bin) in the spontaneous activity of neurons located within the insular cortex, while there was a significant decrease in gamma-aminobutyric acid (GABA) levels measured in IC dialysate. Middle cerebral artery occlusion (MCAO) resulted in a biphasic response consisting of a transient increase in the extracellular concentration of glutamate, aspartate, and GABA, followed by sustained elevations in glutamate and aspartate, but reduced GABA levels 4 h post-MCAO. MCAO also resulted in a significant increase in neuronal activity in the IC (from 28 +/- 9 to 120 +/- 88 spikes/bin). This MCAO-induced excitation was completely blocked following the prior intravenous administration of estrogen. Systemic estrogen administration also resulted in a delay in the progression and decrease in the final infarct volume by approximately 56%. Taken together, these results suggest that under normal conditions, estrogen excites neurons in the insular cortex by decreasing GABA release (disinhibition) and it plays a role in attenuating the MCAO-induced excitability and death of these neurons.
Saleh
Tarek M
TM
Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Canada. tsaleh@upei.ca
Connell
Barry J
BJ
Legge
Carolyn
C
Cribb
Alastair E
AE
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D009498:Neurotoxins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D004967:Estrogens; D018696:Neuroprotective Agents; D009498:Neurotoxins; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid