Spreading depression-like depolarization and selective vulnerability of neurons. A brief review.
If oxygen is withdrawn from rat hippocampal slices, a spreading depression-like response occurs earlier and is of larger amplitude in the CA1 area than in the dentate gyrus. After reoxygenation, recovery of synaptic transmission correlates inversely with the time spent in spreading depression. Recovery occurs more frequently in dentate gyrus than in CA1. Chlorpromazine and the gangliosides GM1 and AGF2 promote recovery from hypoxic depression of synaptic transmission in CA1. Prevention of irreversible loss of function correlates closely with a shortening of the time spent in spreading depression. If Ca2+ is withdrawn before hypoxia, then synaptic function recovers upon restoration of oxygen and [Ca2+]o, despite prolonged spreading depression. When spreading depression lasting more than 6-9 minutes is induced in fully oxygenated slices by superfusion with high-K+ solution, then transient recovery is followed by long-lasting loss of synaptic function. In intact brain of anesthetized rats, synaptic transmission in CA1 recovers after spreading depression-like depolarization lasting more than 30 minutes, but is lost irreversibly after 60 minutes. We conclude that entry of Ca2+ into neurons caused by spreading depression-like depolarization is important in the selective vulnerability of neurons; the duration of depolarization is critical to cell survival; and in the presence of a normal blood supply, neurons resist protracted spreading depression-like depolarization.
Somjen
G G
GG
Division of Physiology, Duke University Medical Center, Durham, N.C. 27710.
Aitken
P G
PG
Balestrino
M
M
Herreras
O
O
Kawasaki
K
K
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004594:Electrophysiology; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D051381:Rats; D013569:Synapses / Q000378:metabolism*
D011188:Potassium; D010100:Oxygen; D002118:Calcium