Protective effects of ischemic preconditioning against neuronal apoptosis and dendritic injury in the hippocampus are age‐dependent

Abstract

Ischemic preconditioning with non‐lethal ischemia can be protective against lethal forebrain ischemia. We hypothesized that aging may aggravate ischemic susceptibility and reduce brain plasticity against preconditioning. Magnetic resonance diffusion tensor imaging (DTI) is a sensitive tool to detect brain integrity and white matter architecture. This study used DTI and histopathology to investigate the effect of aging on ischemic preconditioning. In this study, adult and middle‐aged male Mongolian gerbils were subjected to non‐lethal 5‐min forebrain ischemia (ischemic preconditioning) or sham‐operation, followed by 3 days of reperfusion, and then lethal 15‐min forebrain ischemia. A 9.4‐Tesla MR imaging system was used to study DTI indices, namely fractional anisotropy (FA), mean diffusivity (MD), and intervoxel coherence (IC) in the hippocampal CA1 and dentate gyrus (DG) areas. In situ expressions of microtubule‐associated protein 2 (MAP2, dendritic marker protein) and apoptosis were also examined. The 5‐min ischemia did not cause dendritic and neuronal injury and any significant change in DTI indices and MAP2 in adult and middle‐aged gerbils. The 15‐min ischemia‐induced significant delayed neuronal apoptosis and early dendritic injury evidenced by DTI and MAP2 studies in both CA1 and DG areas with more severe injury in middle‐aged gerbils than adult gerbils. Ischemic preconditioning could improve neuronal apoptosis in CA1 area and dendritic integrity in both CA1 and DG areas with better improvement in adult gerbils than middle‐aged gerbils. This study thus suggests an age‐dependent protective effect of ischemic preconditioning against both neuronal apoptosis and dendritic injury in hippocampus after forebrain ischemia.

Higher cerebral small vessel disease burden is associated with smaller hematoma volume in mixed‐location intracerebral hemorrhage

“…Taken together, cerebral white matter might be a possible epicenter for brain protection and could heighten brain health by mechanistic pathways 36 . Recently, one experimental study shows that preconditioning non‐lethal ischemia, evaluated by diffusion tensor imaging induces which reflected microstructural changes in white matter, has protective effect on neuronal injury following subsequent lethal ischemia 37 . Although there is no animal research on the effect of white matter on following lethal ICH up to now, we hypothesize that this protective effect of non‐lethal ischemia also exists in ICH, which needs to be verified in future experimental studies.…”

DUSP6 Deficiency Attenuates Neurodegeneration after Global Cerebral Ischemia

“…Ischemic preconditioning has gained attention as a potential neuroprotective therapy. It is defined as a state produced by brief episodes of sublethal ischemic stress that protects cells from a subsequent episode of potentially lethal ischemia [30,31]. ERK1/2 has been shown to play a protective role in ischemic preconditioning [8,30,31].…”

“…It is defined as a state produced by brief episodes of sublethal ischemic stress that protects cells from a subsequent episode of potentially lethal ischemia [30,31]. ERK1/2 has been shown to play a protective role in ischemic preconditioning [8,30,31]. Preconditioning with mild tGCI for 3 min enhanced the phosphorylation of Erk1/2 in the CA1 region of the rat hippocampus [32].…”

Comparative Characteristics of the Ultrastructure of the Pyramidal Neurons of the Parietal Cortex in Cerebral Ischemia of Varying Severity

“…in neuronal organelles [10][11][12][13][14][15][16][17]. At the same time, with a 7-day interval between dressings, these ultra-structural changes were minimal, even hypertrophy of the cistern of the endoplasmic reticulum was noted.…”