Biomedical Engineering Reference
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Numerical analysis and mathematical techniques were utilized to identify
[Ca 2+ ] i oscillations in mixed primary cultures of cortical neurons and astrocytes.
We found that stimulation of cells with 50 mMKCl followed by glutamate induced
synchronized and non-synchronized [Ca2+]i 2+ ] i oscillations. In contrast, addition of
the gamma-aminobutyric acid (GABA) receptor antagonist bicuculline, converted
spontaneously oscillating neurons into highly synchronized small networks (Figure 3) .
Since, GABA receptors are inhibitory, these results indicate that bicuculline is
causing disinhibition, revealing more excitatory behavior, in this case, as revealed
by more synchronized [Ca2+]i 2+ ] i oscillations.
Another level of control for the intact brain includes the blood-brain barrier
(BBB). The BBB is a cellular structure that is composed of endothelial cells. The pres-
ence of tight junctions in the endothelial cells with support from astrocytic end feet
makes the barrier impermeable to substances from the blood stream, thereby maintain-
ing homeostasis (Ma et al., 2005). Many neurological diseases occur as a result of the
dysfunction of the brain endothelium. The breakdown of the barrier may result in a
vicious cycle of brain injury (Bowman et al., 1983). The endothelium lining the brain
microvasculature is different from other vascular endothelia by the presence of tight
junctions and limited permeability with a unique pattern of receptors, transporters, and
ion pumps that protect the barrier from hydrophobic substances (Abbott, 2002). Ad-
enine nucleotides like adenosine triphosphate (ATP), adenosine diphosphate (ADP),
adenosine monophosphate (AMP) and adenosine mediate important signaling events
like inflammatory pathways, neurotransmission, and energy-driven processes, caus-
ing calcium influx into the cell (Gordon et al., 1986). This calcium increase occurs
in the form of a stream of calcium ions coming into the cell, called calcium waves.
These waves provide long-range signaling and act as a control mechanism providing
feedback to events like vasodilation. Hence, the study of these calcium waves on the
microvasculature of the brain provides insight into the role it has on normal brain
function, neurological diseases, and the effect it has on other brain cells (Janigro et al.,
1994). As shown in Figure 4, we are utilizing rat brain microvascularendothelial cells
(RBMVECs) in vitro which show intrinsic morphologies such as curved and circular
areas which may reflect their function in vivo of making up blood vessels.
Figure 4. Rat brain microvascular endothelial cells demonstrating differentiation in vitro. Left panel
shows cells at original magnification of 40x. Right panel shows a zoomed area of the left panel,
original magnification= 100x.
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