Biology Reference
In-Depth Information
2.
Manganese-enhanced magnetic resonance imaging to detect
gliosis.
In experimental studies, manganese chloride (MnCl
2
) is increas-
ingly being used as a positive contrast agent in manganese-
enhanced magnetic resonance imaging (MEMRI) that is
sensitive to biological brain processes. Several applications of
MEMRI have been recently developed. Since the Mn
2+
ion can
enter cells via calcium channels, imaging protocols have been
developed to examine activation-induced regional brain
activity. Also, direct injection of MnCl
2
into specifi c brain
regions enables the use of MEMRI for anterograde mapping
and this protocol has been used to detail connections of several
brain pathways. The third application of MEMRI is as a whole
brain contrast agent after peripheral injection as a new method
of molecular imaging to characterize anatomical changes in
brain regions (
15
). Recently, an MEMRI protocol using whole
brain contrast was developed to evaluate reactive astrocytosis
after ischemic brain injury in rats (
16
). In this report, it was
hypothesized that since glutamine synthetase, an enzyme
located primarily in astrocyte, requires Mn that reactive
astrocytes would accelerate Mn uptake and accumulation that
could be detected using Mn-enhanced T1 (longitudinal relax-
ation time) weighted MRI. They demonstrated that MEMRI
reliably detected reactive gliosis and confi rmed the MRI fi nd-
ings with corresponding histochemical evaluation of GFAP-
immunoreactivity. The MEMRI was particularly reliable in
detecting gliosis at 11 and 22 days post-infarct (
16
). Since Mn,
particularly at high concentrations, is toxic to brain tissue,
MEMRI is not anticipated to be developed as a clinical imaging
technique. However, the experimental studies demonstrate
good agreement between the MEMRI signal and GFAP-
positive reactive astrocytes after experimental brain injury
which suggests that MEMRI could be used as a new experi-
mental technique to measure astrogliosis that potentially could
be applied to repeated evaluations or longitudinal studies in
living animals.
3.
Electrophysiology evaluation of inwardly rectifying potassium
currents Kir4.1 in astrocytes
.
As mentioned above, the precise signaling pathways that regu-
late reactive astrogliosis remain unknown; yet, a growing body
of evidence suggests that alteration in potassium (K
+
) infl ux in
astrocytes is critical. It is well established that the highly nega-
tive resting membrane potential and high K
+
permeability of
astrocytes is maintained by the inwardly rectifying K
+
channel
Kir4.1 (
17, 18
). Moreover, Kir4.1 is the channel that supports
K
+
spatial buffering and homeostasis, both vital astrocyte
functions that maintain normal neuronal fi ring (
18
). Clues to the
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