Altered pattern of light transmittance and resistance to AMPA-induced swelling in the dentate gyrus of the epileptic hippocampus.
Glutamate receptor-mediated changes in light transmittance were imaged in the dentate gyri of the epileptic hippocampi, taken from patients with temporal lobe epilepsy and the rat pilocarpine model, to investigate epilepsy-associated alterations in activity-induced cell swelling. A static pattern of light transmittance corresponded to the layered structure of dentate gyrus and reflected epilepsy-associated alterations. Hypoosmotic stress produced more than 35% of dynamic changes in the increase of light transmittance as a reflection of osmotic swelling in the epileptic dentate gyri. This degree of increase was not different from the increase observed in control dentate gyri, suggesting that the capability of osmotically regulating cell volume was preserved in the epileptic dentate gyri. In contrast, alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) induced activity-dependent swelling and an increase in light transmittance by 60.5% in the control dentate gyri, whereas the degree of increase in the epileptic dentate gyri remained 17.9% in response to AMPA. Selective attenuation of light transmittance in response to AMPA in the epileptic but not control dentate gyri suggested a possible alteration in the swelling properties of the epileptic dentate gyri that are linked to the AMPA receptor activation. Surviving cells in the epileptic hippocampus may have a mechanism of downregulating neuronal activity-dependent swelling to maintain optimal cell volume during repeated network hyperexcitation in epilepsy.
Isokawa
M
M
Brain Research Institute and Department of Neurology, University of California, Los Angeles, USA. misokawa@mednet.ucla.edu
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000328:Adult; D000818:Animals; D001929:Brain Edema / Q000473:pathology / Q000503:physiopathology*; D018891:Dentate Gyrus / Q000473:pathology / Q000503:physiopathology*; D004833:Epilepsy, Temporal Lobe / Q000473:pathology / Q000503:physiopathology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D008027:Light; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000473:pathology / Q000502:physiology; D055095:Optics and Photonics; D009924:Organ Culture Techniques; D009997:Osmotic Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D018698:Glutamic Acid; D013779:Tetrodotoxin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid