Apoptosis and Acute Brain Ischemia in Ischemic Stroke

Abstract

Apoptosis may contribute to a significant proportion of neuron death following acute brain ischemia (ABI), but the underlying mechanisms are still not fully understood. Brain ischemia may lead to stroke, which is one of the main causes of long-term morbidity and mortality in both developed and developing countries. Therefore, stroke prevention and treatment is clinically important. There are two important separate areas of the brain during ABI: the ischemic core and the ischemic penumbra. The ischemic core of the brain experiences a sudden reduction of blood flow, just minutes after ischemic attack with irreversible injury and subsequent cell death. On the other hand, apoptosis within the ischemic penumbra may occur after several hours or days, while necrosis starts in the first hours after the onset of ABI in the ischemic core. ABI is characterized by key molecular events that initiate apoptosis in many cells, such as overproduction of free radicals, Ca2+ overload and excitotoxicity. These changes in cellular homeostasis may trigger either necrosis or apoptosis, which often depends on cell type, cell age, and location in the brain. Apoptosis results in DNA fragmentation, degradation of cytoskeletal and nuclear proteins, cross-linking of proteins, formation of apoptotic bodies, expression of ligands for phagocytic cell receptors and finally uptake by phagocytic cells. This review focuses on recent findings based on animal and human studies regarding the apoptotic mechanisms of neuronal death following ABI and the development of potential neuroprotective agents that reduce morbidity. The effects of statins on stroke prevention and treatment as well as on apoptotic mediators are also considered.

Neural Stem Cells Expressing bFGF Reduce Brain Damage and Restore Sensorimotor Function after Neonatal Hypoxia-Ischemia

“…Mechanistic studies had revealed that the apoptosis of neuron in hippocampus, corpus striatum and cortex was the causal events leading to sensorimotor dysfunction after HI [33, 34]. In this study, we had performed cylinder rearing test at 14, 21, 28 and 35 days after HI.…”

Z‐Guggulsterone attenuates astrocytes‐mediated neuroinflammation after ischemia by inhibiting toll‐like receptor 4 pathway

“…After the onset of ischemia, the brain cells suffer depletion of energy supply, excessive accumulation of intracellular calcium, overproduction of free radicals, and potentiation of inflammatory responses (Li et al 2015a;Hoque et al 2016). These events initiate a complex sequence of signaling cascades that eventually result in neuronal dysfunction and cell death by necrosis or apoptosis (Radak et al 2017). In this study, Z-GS remarkably improved the neurological outcome and decreased the infarct volume compared with the MCAO group.…”

“…These events initiate a complex sequence of signaling cascades that eventually result in neuronal dysfunction and cell death by necrosis or apoptosis (Radak et al . ). In this study, Z‐GS remarkably improved the neurological outcome and decreased the infarct volume compared with the MCAO group.…”

Isolation and quantification of blood apoptotic bodies in neurological patients

“…It should be highlighted that the isolation procedure of unbroken apoptotic bodies from neurological patients blood samples could be of great utility for in vivo study of apoptosis in pathologies, such as cerebral ischemia, multiple sclerosis and Parkinson´s disease, in which alteration of such cell death type has been identified as the main mechanism involved [9][10][11][12]. Specifically, the quantification of circulating isolated apoptotic bodies would potentially serve as a non-invasive tool for determining the degree of apoptotic cell death that has occurred in a particular neurological patient, which is, in fact, highly relevant to the understanding and treatment of such human diseases.…”

“…It is now becoming evident that an increasing number of pathological situations can be related to aberrant apoptosis, such as cerebrovascular and neurodegenerative diseases [9][10][11][12]. Thus, the evaluation of the apoptotic processes, in these neurological diseases would be useful in daily clinical practice, since it would allow an earlier and more accurate prognosis, more effective monitoring of evolution of the disease, and the selection of the most appropriate treatment for each patient.…”