Cerebral ischemia causes dysregulation of synaptic adhesion in mouse synaptosomes.

Synaptic pathology is observed during hypoxic events in the central nervous system in the form of altered dendrite structure and conductance changes. These alterations are rapidly reversible, on the return of normoxia, but are thought to initiate subsequent neuronal cell death. To characterize the effects of hypoxia on regulators of synaptic stability, we examined the temporal expression of cell adhesion molecules (CAMs) in synaptosomes after transient middle cerebral artery occlusion (MCAO) in mice.

Cerebral ischemia induces neuronal expression of novel VL30 mouse retrotransposons bound to polyribosomes.

Mammalian genomes are burdened with a large heterogeneous group of endogenous replication defective retroviruses (retrotransposons). Previously, we identified a transcript resembling a virus-like 30S (VL30) retrotransposon increasing in mouse brain following transient cerebral ischemia. Paradoxically, this non-coding RNA was found bound to polyribosomes.

Translation-state analysis of gene expression in mouse brain after focal ischemia.

Confounding any genome-scale analysis of gene expression after cerebral ischemia is massive suppression of protein synthesis. This inefficient translation questions the utility of examining profiles of total transcripts. Our approach to such postischemic gene profiling in the mouse by microarray analysis was to concentrate on those mRNAs bound to polyribosomes.

Absence of the transcription factor E2F1 attenuates brain injury and improves behavior after focal ischemia in mice.

Because of observations that cultured neurons from mice deficient in the transcription factor E2F1 exhibit resistance after treatment with a wide variety of cell-death inducers, the authors investigated whether resistance extended to a cerebral ischemic insult. No differences in cerebral blood flow or physiologic parameters were observed in the mutant E2F1 littermates after the focal ligation. After 2 hours of left middle cerebral artery occlusion and 1 day of reperfusion, a 33% smaller infarct (P < 0.

Molecular mechanisms of cerebral ischemia-induced neuronal death.

The mode of neuronal death caused by cerebral ischemia and reperfusion appears on the continuum between the poles of catastrophic necrosis and apoptosis: ischemic neurons exhibit many biochemical hallmarks of apoptosis but remain cytologically necrotic. The position on this continuum may be modulated by the severity of the ischemic insult. The ischemia-induced neuronal death is an active process (energy dependent) and is the result of activation of cascades of detrimental biochemical events that include perturbion of calcium homeostasis leading to increased excitotoxicity, malfunction of endoplasmic reticulum and mitochondria, elevation of oxidative stress causing DNA damage, alteration in proapoptotic gene expression, and activation of the effector cysteine proteases (caspases) and endonucleases leading to the final degradation of the genome.