Alterations of hippocampal postsynaptic densities following transient ischemia

A transient interruption in cerebral blood flow can lead to delayed neurona l death in certain vulnerable cell populations several days after blood flo w is restored. Among the most vulnerable cell populations in: the forebrain are hippocampal CA1 pyramidal neurons, which die between 48-72 h after the ischemic insult. Neurons in the dentate gyrus and area CA3 are relatively resistant, and will recover from the same insult. Uncovering the factors th at render some neuronal populations vulnerable to transient ischemia is key to understanding mechanisms leading to cell death and to developing therap eutic interventions, By applying selective staining and three-dimensional ( 3D) imaging with electron tomography, we uncovered dramatic structural modi fications in postsynaptic densities in the postischemic brain. Postsynaptic densities in the postischemic brain appeared both thicker and less condens ed than those from sham-operated controls. Although the class of synapse co uld not be determined with the methods used, most are likely to be glutamat ergic synapses onto dendritic spines, because the majority of synapses in t he region examined belong to this class. Further analysis using electron to mography to examine the 3D structure of postsynaptic densities revealed deg enerative changes, as evidenced by an overall loosening of the normally com pact structure. Synaptic modifications were particularly severe and persist ent in hippocampal area CA1 compared to the dentate gyrus. These structural modifications correlate well with biochemical and physiological studies in dicating that alterations in synaptic transmission occur in the postischemi c brain. The combination of selective staining and 3D reconstruction provid es a valuable tool for revealing aspects of synaptic morphology not apparen t from standard electron microscopic evaluation. Hippocampus 2000;10:610-61 6. (C) 2000 Wiley-Liss, Inc.