Apoptotic Cell Death Following Traumatic Injury to the Central Nervous System

Abstract

Apoptotic cell death is a fundamental and highly regulated biological process in which a cell is instructed to actively participate in its own demise. This process of cellular suicide is activated by developmental and environmental cues and normally plays an essential role in eliminating superfluous, damaged, and senescent cells of many tissue types. In recent years, a number of experimental studies have provided evidence of widespread neuronal and glial apoptosis following injury to the central nervous system (CNS). These studies indicate that injury-induced apoptosis can be detected from hours to days following injury and may contribute to neurological dysfunction. Given these findings, understanding the biochemical signaling events controlling apoptosis is a first step towards developing therapeutic agents that target this cell death process. This review will focus on molecular cell death pathways that are responsible for generating the apoptotic phenotype. It will also summarize what is currently known about the apoptotic signals that are activated in the injured CNS, and what potential strategies might be pursued to reduce this cell death process as a means to promote functional recovery.

Noninvasive molecular imaging of apoptosis in vivo using a modified firefly luciferase substrate, Z-DEVD-aminoluciferin

“…As mentioned above, cellular apoptosis not only has an essential role in normal physiology and development but is also instrumental in a number of disorders, including Parkinson's, Alzheimer's, cerebral ischemia, and many cardiovascular diseases. [5][6][7] Therefore, this probe may also have utility in applications across numerous therapeutic targets and research disciplines through the usage of luciferase-expressing cell lines or transgenic animal models specific to these disease states.…”

“…5 Furthermore, many studies have reported extensive neuronal and glial apoptosis after injury to the central nervous system. 6 Apoptosis is also an important process fundamental to many diseases of the cardiovascular system, including chronic heart failure, atherosclerotic vascular disease, and myocardial ischemia and reperfusion injury. 7 Therefore, development of imaging probes targeting cells undergoing apoptosis may allow evaluation of therapeutic efficacy in a wide range of preclinical applications.…”

Effect of Endogenous Androgens on 17β-Estradiol-Mediated Protection after Spinal Cord Injury in Male Rats

“…It has been over a decade since the earliest reports of apoptotic cell death in SCI, and reduction and=or regulation of apoptosis remains a therapeutic target (Beattie, 2004;Springer, 2002). The Bcl-2 protein family includes both proand anti-apoptotic members, which regulate the permeability of the mitochondrial outer membrane through control of the formation of a permeability transition pore (Antignani and Youle, 2006).…”

Selective Loss of Catecholaminergic Wake–Active Neurons in a Murine Sleep Apnea Model

“…Caspase-3 is a proteolytic enzyme that, when activated, destroys numerous critical cellular proteins; this enzyme is considered one of the key executioner proteins of apoptosis (Cohen, 1997;Springer, 2002;Rami, 2003). Thus, whereas cleaved caspase-3 is upregulated transiently in synaptic remodeling (Huesmann and Clayton, 2006), prolonged activation of caspase-3 is considered a marker of neural injury in models of ischemia, trauma, and neurodegeneration (Cohen, 1997;Springer, 2002;Rami, 2003). Additionally, cleaved caspase-3 has been identified in cortical neurons of animals exposed to LTIH (Xu et al, 2004) and thus may highlight injured wake-active neurons.…”