Early recovery of protein synthesis following ischemia in hippocampal neurons with induced tolerance in the gerbil

Abstract

Following brief cerebral ischemia, tolerance to subsequent ischemia is induced in the hippocampal neurons. In this experiment, recovery of protein synthesis was investigated autoradiographically in gerbils with induced tolerance. The animals were subjected to single forebrain ischemia for 5 min (5-min ischemia group) or 2 min (2-min ischemia group). To observe the effect of tolerance acquisition, double forebrain ischemia (double ischemia group), 2-min ischemia followed by 5-min ischemia was induced 2 days later. At various recirculation periods (90 min, 6 h, 1 day, and 4 days following ischemia), animals received a single dose of L-[2,3-3H]valine. In the 5-min ischemia group, protein synthesis in the CA1 sector was severely suppressed during the period from 90 min to 1 day of recirculation and never returned to the normal level even at 4 day of recirculation. In the 2-min ischemia group, protein synthesis recovered gradually and returned to near normal at 4 days of recirculation. On the other hand, in the double ischemia group, recovery of protein synthesis in the CA1 sector was rapid. At 1 day of recirculation, protein synthesis returned to near normal. Protein synthesis in the CA2 sector was inhibited during the 4 days of recirculation in this group. The present study revealed an early recovery of protein synthesis in the hippocampal CA1 neurons in the gerbil with induced tolerance. We suggest that recovery of protein synthesis is essential for the survival of neurons exposed to transient ischemia.

Transient cerebral ischaemia in mongolian gerbils pre-exposed to hypoxia

“…In the normoxic group, 5-minute-forebrain ischaemia induced delayed neuronal death. These changes were similar to those reported in previous reports [13,14,22]. In the hypoxic group, the CAt pyramidal cells were more damaged after 5-minute-forebrain ischaemia than those in the normoxic group.…”

“…It has been reported that neurotoxic actions of synaptically released excitatory amino-acids play a crucial role in delayed neuronal damage [23,28], but the mechanism is not fully understood. Pre-treatment of the brain with a sublethal stress has been reported to increase neuronal tolerance to a subsequent episode of cerebral ischaemia [3,15,22]. In an in vitro study, hippocampal neurons have been reported to become more vulnerable to glutamate neurotoxicity after subcritical hypoxia [18].…”

Effect of ischemic preconditioning on cerebral blood flow after subsequent lethal ischemia in gerbils

“…However, Nakagomi et al (1993) showed that the recovery rate of protein synthesis in gerbil brain after ischemic preconditioning is more rapid than that in nonpreconditioned gerbils. These results indicate that ischemic preconditioning contributes to the early recovery of protein synthesis.…”

Calpain-induced Proteolysis After Transient Global Cerebral Ischemia and Ischemic Tolerance in a Rat Model

“…In addition, preconditioning serves to genetically reprogram the response to ischemia [29]. Nonetheless, it is important to note that translation is deeply inhibited during early post-ischemic reperfusion [35], and is only partially restored by IT [31,51,52]. Therefore, translation might modulate the synthesis of the protein products of these inducible genes, and be responsible for the observed discrepancy between the messenger RNA (mRNA) and protein expression patterns [53].…”