Assessments of Reactive Astrogliosis Following CNS Injuries - Animal Models of Acute Neurological Injuries: Injury and Mechanistic Assessments - page 52

extracellular ionic homeostasis, removing extracellular glutamate,
regulating blood fl ow, and are active signaling partners to neurons
in synaptic function and plasticity ( 1-3 ). Under pathological
conditions, such as acute traumatic brain injury (TBI) or spinal
cord injury (SCI), ischemia, infection, neurodegeneration, or seizure/
epilepsy, astrocytes become reactive. However, the precise defi ni-
tion of reactive astrogliosis remains an area of active scientifi c
debate and ongoing research; accordingly, the reader is directed to
an excellent recent review of the issues surrounding defi ning
reactive astrogliosis ( 2 ). The defi nition of reactive astrogliosis
proposed in this review contains four critical components. First is
that reactive astrogliosis is a spectrum of changes that occurs in
response to a graded severities of injury/insult, and secondly that
the changes in astrocytes are dependent on the nature and severity
of the injury. Additionally, the astrogliotic response is regulated by
the context in which it occurs. Lastly, the functional consequences
of reactive astrogliosis occur through both gain and loss of astrocyte
functions and can have either benefi cial or detrimental conse-
quences to surrounding tissue. This defi nition emphasizes the
importance of understanding the attributes and functional conse-
quences of reactive astrogliosis in the context of the CNS insult
and underscores the importance of studying reactive astrogliosis in
response to different types and severities of CNS insults ( 2 ).

1.2. Histological
Techniques to Evaluate
Reactive Astrogliosis

Although the molecular, biochemical, and functional changes
associated with reactive gliosis are not fully elucidated, the mor-
phological changes are better described ( 4 ). One morphological
hallmark of reactive astrogliosis is the up-regulation of the inter-
mediate fi lament proteins glial fi brillary acidic protein (GFAP) and
vimentin which is often accompanied by a thickening of the main
astrocyte processes, or hypertrophy ( 5, 6 ). In healthy tissue, GFAP
is the main intermediate fi lament expressed and the levels of vimen-
tin are typically low and depend upon the subpopulation of astro-
cytes examined ( 6 ). However, the expression of both these proteins
is signifi cantly increased in reactive astrogliosis albeit heterogeneity
and regional differences remain ( 7, 8 ). Thus, one of the most
commonly used techniques to measure reactive gliosis is to evaluate
the expression of GFAP. As demonstrated by a recent review of
research studies cited in PubMed from January 2008 until March
2010 obtained by searching the keywords “gliosis and brain injury”
and “gliosis and spinal cord injury,” a vast majority of the published
work uses evaluation of GFAP expression as the main outcome
measure for gliosis (Fig. 1 ). It is important to note that in both
non-reactive and reactive astrocytes, the expression of GFAP
protein that can be detected by immunohistochemistry (IHC) is
limited to the proximal portions of cell processes which means that
the complexity of the fi ne distal processes and their associated
volume cannot be visualized with GFAP-IHC (for review, see ref. ( 6 ).