Astroglia: Important mediators of traumatic brain injury
Introduction
Traumatic brain injury (TBI) research to date has focused almost exclusively on the pathophysiology of injured neurons with very little attention paid to non-neuronal cells. This near-exclusive focus on neuroprotection likely reflects the predominant paradigm of the neuroscience community as a whole, which characterized glial cells as a specialized type of connective tissue that merely provided support for the neurons. However in the past decade, exciting discoveries have challenged this century-old view of passive glial cells and have led to a reinterpretation of the role of glial cells in central nervous system (CNS) biology and pathology. In this chapter we review several lines of evidence, indicating that glial cells, particularly astrocytes, are active partners to neurons in the brain, and summarize recent findings which detail the significance of astrocyte pathology in traumatic brain injury.
Section snippets
Astrocytes in normal brain function: recasting an old “star”
One line of evidence that astrocytes are more than supportive connective tissue comes from recent detailed analyses of the cellular morphology. A unique morphological feature of astrocytes is that nearly the entire cell surface is covered with processes that extend and become lamellae or filopodia as indicated by three-dimensional reconstruction of electron micrographs. Most lamellae and filopodia originate from processes, which, like the cell body, contain organelles and cytoskeletal elements;
Revisiting and revising the “Classical View” of astrocytes in CNS trauma
As discussed in the introduction, TBI research to date has focused mainly on neuroprotection and given little consideration to the role of glial cells in injury. This has significant implications for the understanding of brain pathology after TBI since the population of glial cells in brain is actually much larger than neurons. Furthermore, the importance of the complex communication and interaction between astrocytes and neurons described above are becoming more apparent in normal brain
Unraveling the mechanisms of acute astrocyte damage with in vitro mechanical injury
It is clear from the studies described above that in vivo experimental TBI or ischemia produces rapid and profound damage to astrocytes. Moreover, several in vitro models of ischemia also show acute astrocyte pathology. Additionally, several of the astrocytic intracellular events occurring acutely after TBI have been characterized in a series of in vitro studies using a mechanical injury model developed by Ellis et al. (1995). In this model, cells are grown on a membrane that is subjected to a
Conclusion
With some notable exceptions such as the study of gliosis and astrocytic swelling, most TBI research has generally focused on the pathophysiology of neurons. However, many recent developments in the field of glial biology demonstrate the active nature of neuronal-astrocyte signaling indicating the vital importance of astrocytes in normal brain function. Furthermore, recent studies in Neurotrauma demonstrate the vulnerability of astrocytes to CNS insults. Therefore, defining the time course of
Acknowledgments
Support provided by UCD Health Systems Research Award (CLF), NIH NS29995 (BGL), NIH NS45136 (BGL).
References (188)
- et al.
New roles for astrocytes: gap junction hemichannels have something to communicate
Trends Neurosci.
(2003) - et al.
A neuron-glia signalling network in the active brain
Curr. Opin. Neurobiol.
(2001) - et al.
Ca2+ waves in astrocytes
Cell Calcium
(1991) - et al.
Compartmentation of brain glutamate metabolism in neurons and glia
J. Nutr.
(2000) The high affinity uptake system for excitatory amino acids in the brain
Prog. Neurobiol.
(1994)Glutamate uptake
Prog. Neurobiol.
(2001)- et al.
Neuronal activity triggers calcium waves in hippocampal astrocyte networks
Neuron
(1992) - et al.
Aniracetam attenuates apoptosis of astrocytes subjected to simulated ischemia in vitro
Neurotoxicology
(2002) - et al.
Control of gap-junctional communication in astrocytic networks
Trends Neurosci.
(1996) - et al.
Kynurenate is neuroprotective following experimental brain injury in the rat
Brain Res.
(1994)