Hypertonic environment prevents depolarization and improves functional recovery from hypoxia in hippocampal slices.
Treatments that postpone hypoxic spreading depression (SD)-like depolarization (also called anoxic depolarization) facilitate recovery of function after transient cerebral hypoxia. Hypertonia reduces cerebral excitability, and we tested whether it also offers protection against SD-like depolarization and hypoxia. Oxygen was withdrawn from hippocampal slices bathed in normal artificial cerebrospinal fluid (ACSF) and, simultaneously, from slices cut from the same hippocampus but bathed in strongly hypertonic ACSF. Extracellular osmolarity (pi(o)) was increased by adding 100 mM mannitol or fructose to ACSF. Slices in normal pi(o) underwent SD-like negative extracellular voltage shift (delta Vo). The hypertonic slices usually showed no SD-like delta Vo but only a small, gradual negative voltage shift. Hypertonia also prevented the precipitate drop of interstitial calcium level ([Ca2+]o). When oxygenation and normal osmolarity were restored, synaptic transmission in the previously hypertonic slices recovered completely, but 3 h after reoxygenation orthodromically transmitted population spikes of the control slices recovered only 25.1% of the initial control amplitude. We conclude that hypertonic treatment during hypoxia improves subsequent recovery of synaptic function. The protection is probably due to the prevention of calcium uptake by blocking the SD-like depolarization, with the prevention of hypoxic cell swelling playing a lesser role.
Huang
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Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, USA.
Aitken
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Somjen
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D000818:Animals; D013181:Cortical Spreading Depression / Q000502:physiology; D004594:Electrophysiology; D005632:Fructose / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D006982:Hypertonic Solutions / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D006982:Hypertonic Solutions; D005632:Fructose; D008353:Mannitol; D010100:Oxygen