Ultrastructural investigation of the CA1 region of the hippocampus after transient cerebral ischemia in gerbils

Abstract

Ultrastructural damage leading to delayed neuronal death was investigated in the mid-CA1 region of the hippocampus from the stratum (str.) moleculare to oriens after transient bilateral forebrain ischemia in Mongolian gerbils. After ischemia for 5 min without recirculation, mild swelling of the peripheral part of the apical and basal dendrites was already apparent in the str. moleculare and str. oriens. Mitochondria in the dendrites were also swollen in the same area. During recirculation for 12 h to 3 days, swelling of the dendritic cytoplasm persisted with formation of microvacuoles, but swelling of mitochondria receded. Microvacuolation and loss of microtubules were also observed in the proximal part of the dendrites during this period, and swelling and disruption of internal cristae were observed in mitochondria after recirculation for 3 days. The dendrites became severely degenerated after recirculation for 4 days. In the pyramidal cell bodies, no abnormality was observed at the end of ischemia for 5 min, but disaggregation of polyribosomes and swelling of the endoplasmic reticulum were observed 12 h after recirculation. Proliferation of the endoplasmic reticulum in parallel arrays occurred after recirculation for 1 day and persisted. Severe degeneration of the pyramidal cell bodies was obvious after recirculation for 4 days. The findings observed in the present investigation suggested that the neuronal structure most vulnerable to ischemia was the peripheral part of the dendrites and postischemic neuronal damage occurred early in this part of the dendrites.

Temporal Profiles of Axon Terminals, Synapses and Spines in the Ischemic Penumbra of the Cerebral Cortex

“…14 Also an EM study on the CA-1 showed degeneration and shrinkage of dendrite around 3 to 4 days after temporary ischemia. [15][16][17] In the present study, we found that the neurites degenerated around 4 days and that their thickness increased, in association with the recovery to normal of the number and percent volume of spines, at 12 weeks after the insult.…”

“…10 Changes in spines and dendrites were studied by time-lapse microscopy after temporary anoxia/hypoglycemia in cell culture, 11,12 by light microscopy (LMS) of Golgi stain-impregnated sections of the 3rd to 5th cortical layers of the cerebral cortex after temporary ischemia, 13 and by EM after temporary hypoxia/glycemia in hippocampal slice. 10 Changes in CA-1 dendrites after temporary ischemia were investigated by light microscopy of horseradish peroxidase-injected specimens, 14 by EM after temporary ischemia in CA-1, 15,16 and by EM of Golgi stain-impregnated cerebral cortex after temporary ischemia for 20 minutes. 17 Almost all of the above studies were performed in connection with delayed ischemia-induced injury to CA-1 neurons, and observations were made during a short period after ischemia.…”

Mechanisms of Neuronal Apoptosis In Vivo

“…1. 2000 NEURONAL APOPTOSIS AND mGluR AFTER ISCHEMIA 165 sidering the postsynaptic, somatodendritic localization of these proteins (Martin et al, 1992; Blue et al, 1997) and the rapid damage to dendritic membranes and the cytoskeletal proteolysis that occur in these neurons after ischemia (Kitagawa et al, 1989;Yamamoto et al, 1990). These abnormalities further support our conclusion that hippocampal pyramidal neurons and Purkinje cells undergo necrosis after ischemia.…”

“…These structural changes are consistent with the finding that total protein synthesis is severely reduced by 6 hours after transient global forebrain ischemia and is reduced persistently in CA1 neurons, with the vast majority of pyramidal neurons never regaining their normal biosynthetic activity (Thilmann et al, 1986; Johansen and Diemer, 1990; Furuta et al, 1993). Cytoskeletal disintegration also occurs early after ischemia, particularly in dendrites, before the degeneration of neuronal cell bodies (Kitagawa et al, 1989;Yamamoto et al, 1990). This rapid disassembly and proteolysis of the cytoskeleton after ischemia (Kitagawa et al, 1989) contrast with the organized structure of the cytoskeleton and the cytoskeletal accumulation in neurons undergoing apoptosis (see Fig.…”

Continuing Postischemic Neuronal Death in CA1

“…Early changes such as disaggregation of polyribosomes and dilated organelles 1,4,5 precede the eventual death of CA1 cells, which exhibits the typical features of necrosis (ie, mitochondrial flocculent densities, clumped chromatin, membrane breaks). [4][5][6] However, studies assessing DNA fragmentation after global ischemia have suggested biochemical See Editorial Comment, page 667 evidence for apoptosis. [7][8][9][10][11] In addition, findings of CA1 neuroprotection with protein synthesis inhibitors, such as cycloheximide or anisomycin, [12][13][14] suggest pharmacological evidence for apoptosis since this may depend on new protein synthesis.…”