Pattern of neuronal loss in the rat hippocampus following experimental cardiac arrest-induced ischemia

The pattern of neuronal loss in the rat hippocampus following 10-min-long c ardiac arrest-induced global ischemia was analyzed using the unbiased, dise ctor morphometric technique and hierarchical sampling. On the third day aft er ischemia, the pyramidal layer of sector CA1 demonstrated significant (27 %) neuronal loss (P<0.05). At this time, no neuronal loss was observed in o ther cornu Ammonis sectors or the granular layer of the dentate gyrus. On t he 14th postischemic day, further neuronal loss in the sector CA1 pyramidal layer was noticed. At this time, this sector contained 31% fewer pyramidal neurons than on the third day (P<0.05) and 58% fewer than in the control g roup (P<0.01). On the 14th day, neuronal loss in other hippocampal subdivis ions also was observed. The pyramidal layer of sector CA3 contained 36% few er neurons than in the control group (P<0.05), whereas the granular layer o f the dentate gyrus contained 40% fewer (P<0.05). The total number of pyram idal neurons in sector CA2 remained unchanged. After the 14th day, no signi ficant alterations in the total number of neurons were observed in any subd ivision of the hippocampus until the 12th month of observation. Unbiased mo rphometric analysis emphasizes the exceptional susceptibility of sector CA1 pyramidal neurons to hypoxia/ischemia but also demonstrates significant ne uronal loss in sector CA3 and the dentate granular layer, previously consid ered 'relatively resistant'. The different timing of neuronal dropout in se ctors CA1 and CA3 and the dentate gyrus may implicate the existence of regi on-related properties, which determine earlier or later reactions to ischem ia. However, the hippocampus has a unique, unidirectional system of intrins ic connections, whereby the majority of dentate granular neuron projections target the sector CA3 pyramidal neurons, which in turn project mostly to s ector GAL. As a result, the early neuronal dropout in sector CA1 may result in retrograde transynaptic degeneration of neurons in other areas. The lac k of neuronal loss in sector CA2 can be explained by the resistance of this sector to ischemia/hypoxia and the fact that this sector is not included i n the major chain of intrahippocampal connections and hence is not affected by retrograde changes. (C) 1999 Elsevier Science BN. All rights reserved.