Postischemic changes of intracellular second messengers in the gerbil brain after long-term survival: An autoradiographic study

Abstract

Receptor autoradiographic and histological techniques were used to investigate the long-term changes that occur in the gerbil brain following the induction of transient cerebral ischemia. Transient ischemia was induced for 3 and 10 min, and animals were allowed to survive for eight months. Autoradiographic analysis of second messenger systems showed that 3-min ischemia caused a significant reduction in [ 3H]inositol-1,4,5-trisphosphate binding in the hippocampal CA1 sector, whereas the alteration in [ 3H]phorbol 12,13-dibutyrate, [ 3H]forskolin and [ 3H] cyclic-AMP bindings was not found in this region. In the striatum, 3-min ischemia caused no significant alteration in [ 3H]phorbol 12,13-dibutyrate, [ 3H]inositol-1,4,5-trisphosphate and [ 3H]forskolin binding sites, whereas the [ 3H]cyclic-AMP binding showed a significant elevation. The thalamus exhibited a significant elevation only in the [ 3H]inositol-1,4,5-trisphosphate binding sites. Following 10-min ischemia, [ 3H]phorbol 12,13-dibutyrate, [ 3H]inositol-1,4,5-trisphosphate and [ 3H]cyclic-AMP binding sites revealed a significant reduction in the hippocampus, whereas the [ 3H]forskolin binding showed a significant elevation in this area. In the striatum, 10-min ischemia caused no significant alteration in [ 3H]phorbol 12,13-dibutyrate, [ 3H]inositoll, 4,5-trisphosphate and [ 3H]cyclic-AMP binding sites. However, marked reduction in the [ 3H]forskolin binding was seen in the striatum. Furthermore, the substantia nigra also exhibited a significant reduction in [ 3H]forskolin binding. Histological studies suggested that 3-min ischemia can produce severe neuronal damage and mild shrinkage to the hippocampal CA1 sector. They also showed that 10-min ischemia can cause severe tissue shrinkage and severe neuronal damage in the hippocampal CA1 sector and hippocampal CA3 sector. Thus, the hippocampal damage following ischemia was not static but progressive. Further, our autoradiographic and histological data suggested that transient ischemia can cause the damage to striatonigral projection in which the distribution of adenylate cyclase is highly concentrated. These results demonstrate that long-term survival following transient cerebral ischemia produces the alteration of second messenger systems particularly in the hippocampal formation in which severe shrinkage was noted and may thus have important functional implications.