Therapeutic window of halothane anesthesia for reversal of delayed neuronal injury in gerbils: relationship to postischemic motor hyperactivity.
The effect of postischemic halothane anesthesia on locomotor activity and delayed neuronal injury in the hippocampal CA1 sector was examined in gerbils subjected to 5-min forebrain ischemia. Locomotor activity was assessed for 48 h after ischemia using an animal activity monitor, and CA1 injury was evaluated by counting the number of surviving neurons following 7 days of recirculation. Sham-treated animals exhibited a slight decrease of motor activity for about 1 day after surgery. Gerbils subjected to ischemia without postischemic halothane anesthesia developed significant motor hyperactivity (18 times higher than control activity) between 1.7 h and 6.7 h of recirculation. Surviving CA1 neurons in this group amounted to only 17% of those in the control animals. Postischemic halothane anesthesia during the initial 1.7 h of recirculation abolished subsequent motor hyperactivity and protected 84% of all CA1 neurons. Postischemic halothane anesthesia during 1.7 h-3.3 h of recirculation and 3.3-5 h of recirculation did not abolish motor hyperactivity except during the period of anesthesia, and did not protect hippocampal CA1 neurons (only 24% and 10% neuronal survival, respectively). These results demonstrate that the therapeutic window of halothane anesthesia for protection of hippocampal injury precedes the phase of locomotor hyperactivity, and that the appearance of the latter predicts delayed neuronal death.
Kuroiwa
T
T
Max-Planck-Institute for Neurological Research, Department of Experimental Neurology, Cologne, F.R.G.
Bonnekoh
P
P
Hossmann
K A
KA
D000758:Anesthesia; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002545:Brain Ischemia / Q000150:complications*; D016923:Cell Death / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D005260:Female; D005849:Gerbillinae; D006221:Halothane; D006624:Hippocampus / Q000098:blood supply; D006948:Hyperkinesis / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009422:Nervous System Diseases / Q000517:prevention & control*; D009474:Neurons / Q000502:physiology*
D006221:Halothane