Biomedical Engineering Reference
In-Depth Information
is co-transported with Na
+
ions). Astrocytic glutamate uptake
prevents excitotoxicity, and in doing so, helps maintain gluta-
mate homeostasis
(11, 12)
. Glutamate and glutamine are more
concentrated respectively in neurons and astrocytes. Glutamate
is used in astrocytes to synthesize glutamine which, in turn, is
a precursor of glutamate synthesis in neurons. Re-establishment
of glutamate reserves (requiring energy input) is essential for
continuous signaling at the glutamatergic nerve terminal. The
glutamate-glutamine cycle, therefore, is a necessary part of overall
cellular excitability
(17)
, but more importantly, links membrane
depolarization to synaptic activity
(11, 12)
. A prudent advisory,
however, to the highlighted events at the nerve terminal is that
synaptic activity is
not
exclusively mediated by digital (i.e., all or
none) signaling alone
(2)
. Membrane potential changes can also
be quite graded (and slow) to produce analog signals which may
also influence activities at the nerve terminal
(18)
.
3. Energy Demand
and Blood Flow
Signaling at the glutamatergic nerve terminal, spanning wide
bandwidths
(19)
, depends on synchronized electrical as well as
chemical events where neurons and astrocytes play complemen-
tary roles
(6, 7)
. Removal of any one step from the rest com-
promises function of the entire system
(11, 12)
. While most of
the energy is expended for moving Na
+
and K
+
ions against
large chemical gradients, a small but non-negligible fraction is
needed for intracellular Ca
2
+
homeostasis and neurotransmitter
recycling/synthesis/repackaging
(6, 7)
. Because activities at the
nerve terminal are in continuous need of energy, demand for it
is
a fundamental requirement
(20)
.
In no other organ is the continuous energy supply more
imperative than in the brain. In humans, the brain is merely 2% of
the body's weight but it consumes more than 20% of the oxida-
tive fuels in the entire body
(21)
and receives nearly 15% of the
cardiac output
(22)
to supply nutrients (i.e., glucose and oxygen).
Furthermore, endogenous energy reserves in the brain - glucose
(1-3 mM
(23)
), oxygen (50-100
μ
M
(24)
), glycogen (2-4 mM
(25)
), and creatine (8-10 mM
(26)
)-areminimal
(27)
.Normal
function, therefore, needs blood circulation to efficiently provide
nutrients (and remove waste) throughout the brain
(28)
.Energy
demand and blood flow are well correlated over different brain
regions
(29)
.
The energetic costs for brain work are mainly met by
ATP derived exclusively from glucose oxidation
(30)
. Glucose
metabolism is limited by phosphorylation, not transport
(31)
.
