Structural Remodeling of Astrocytes in the Injured CNS

Only 23 pages and every neurologist and researcher should be able to recite this to you verbatim.
http://nro.sagepub.com/content/early/2011/10/04/1073858411423441.full.pdf+html?utm_source=neuroscience_A&utm_medium=LandingPage&utm_content=TheNeuroscientist&utm_campaign=1112050
Abstract
Astrocytes respond to all forms of CNS insult and disease by becoming reactive, a nonspecific but highly characteristic
response that involves various morphological and molecular changes. Probably the most recognized aspect of reactive
astrocytes is the formation of a glial scar that impedes axon regeneration. Although the reactive phenotype was first
suggested more than 100 years ago based on morphological changes, the remodeling process is not well understood.
We know little about the actual structure of a reactive astrocyte, how an astrocyte remodels during the progression
of an insult, and how populations of these cells reorganize to form the glial scar. New methods of labeling astrocytes,
along with transgenic mice, allow the complete morphology of reactive astrocytes to be visualized. Recent studies
show that reactivity can induce a remarkable change in the shape of a single astrocyte, that not all astrocytes react in
the same way, and that there is plasticity in the reactive response.
Keywords
protoplasmic, fibrous, reactive astrocytes, review, GFAP, glial scar
Astrocytes are the most abundant nonneuronal cell type
within the brain. They are intimately associated with the
surrounding neurons and blood vessels, and their processes
envelop all cellular components of the CNS. Progress
in our knowledge of astrocytes has lagged our
understanding of neuronal morphology and function. The
reasons may be that astrocytes have traditionally been
thought of as simply filling in the spaces between neurons
and that they do not generate action potentials. We have
learned much about the functional diversity of neurons
with different morphologies, but we are only beginning to
discover the complex and diverse roles of astrocytes.
Astrocytes contact blood vessels and make gap junction
connections with other astrocytes and oligodendrocytes.
They support activities essential for neuronal
function, including promoting synapse formation, regulating
the extracellular concentrations of ions and neurotransmitters,
providing metabolic substrates for
neurons, coupling blood flow to neuronal activity, and
maintaining the blood-brain barrier (Ullian and others
2001; Simard and Nedergaard 2004; Iadecola and
Nedergaard 2007; Pellerin and others 2007; Rouach and
others 2008; Robel and others 2011). Central questions
are whether all astrocytes or just specific types share
these functions and what the relevance is of these differences
to human disease.
Astrocytes alter their morphology in pathological
states. While studying brains from patients with multiple
sclerosis, Carl Frommann described pathological glial
cells in general as larger and having fewer processes compared
to normal glia. He also noted that glial cells were
still present in areas of fiber degeneration. In 1910, Alois
Alzheimer concluded that any type of pathology is accompanied
by a glial response. We now know that astrocytes
respond to multiple forms of CNS insult (trauma, ischemia,
infection, inflammation, neurodegeneration) by
becoming “reactive,” changing their morphology, physiology,
function, and gene expression. This response is
graded; depending on the nature and severity of the insult,
there is a continuum of progressive alterations.
In this review, we focus on the morphological remodeling
of reactive astrocytes. Although the reactive phenotype
was first suggested more than 100 years ago based
on morphological changes, some simple but fundamental
questions remain. What does an individual reactive astrocyte
look like? Do all astrocytes remodel in the same
way, and do all insults produce the same effect? The ability
of reactive astrocytes to remodel and form a glial scar
that impedes axon regeneration led to an overall negative
connotation of the effects of reactivity. Recent work,
however, reveals that they can also play a beneficial role
(Sofroniew 2009; Sofroniew and Vinters 2010). We do
not know how a population of these cells reorganizes to
form the glial scar. How long do these changes last? We
begin by describing the normal morphology and spatial
organization of astrocytes in the gray and white matter
and then discuss how they remodel after insult.