Therapeutic Window of CAl Neuronal Damage Defined by an Ultrashort-Acting Barbiturate After Brain Ischemia in Gerbils

Previous therapeutic studies on the prevention of selective vulnerability of neurons in the hippocampus have suggested that the critical period for induction of delayed neuronal injury occurs early during recirculation. To determine the onset and duration of this period, an ultrashort-acting barbiturate (methohexital) was infused into the left carotid artery of 47 gerbils after various times of recirculation following 10 minutes of bilateral forebrain ischemia. Neuronal density in the left CAl sector was determined 7 days later by counting the number of surviving neurons per millimeter of pyramidal cell layer. In 16 saline-treated gerbils, <10% of the CAl neurons survived the 10 minutes of ischemia. Postischemic carotid infusion of methohexital improved neuronal survival, the degree of improvement depending on the timing and duration of the methohexital infusion. When carried out during the initial 40 minutes of recirculation, methohexital infusion for 10 minutes increased the number of surviving neurons to approximately 60% of that in five sham-operated control gerbils. This increase was significant for infusions carried out between the 10th and 20th minutes (n=6, p<0.05) and between the 30th and 40th minutes («=6,/>< 0.05) of recirculation. Methohexital infusion for 20 minutes increased neuronal survival to 95% and 73% of that in the controls when carried out between the Oth and 20th minutes (n=5, p< 0.005) and between the 20th and 40th minutes (n=5, p< 0.005) of recirculation, respectively. Protection was nonsignificant for 10or 20-minute methohexital infusions carried out after the 40th minute of recirculation. Our results demonstrate that the pathologic processes leading to delayed neuronal injury in the CAl sector are induced during the initial 40 minutes of recirculation and that barbiturates are able to reverse these processes only if given during this period. (Stroke 1990;21:1489-1493)