Biology Reference
In-Depth Information
changing energy needs. Blood vessels in the brain are equipped with control
mechanisms that match oxygen and glucose delivery through blood flow with
the local metabolic demands that are imposed by neural activity (
Iadecola &
Nedergaard, 2007
). A major advance was made by the demonstration that
astrocytes, cells with extensive contacts with both synapses and cerebral
blood vessels, participate in the increases in flow evoked by synaptic activity
(
Takano et al., 2006
).
For neuronal activity to increase the blood flow, the active synapses must
generate signals that act on different segments of the cerebral vasculature. Neural
activity increases the cerebral blood flow that occur within seconds and are
highly restricted to the activated region (
Cox, Woolsey, &Rovainen, 1993
).
Thus, neuronal activity triggers various responses that act together to alter the
delivery of energy substrates to meet the local neuronal needs. Neurovascular
coupling involves the dilation of blood vessels to increase the local blood flow,
while neurometabolic coupling is the stimulation of energy metabolism to keep
up with the cellular consumption of ATP. Neuronal activity also brings about
changes in the permeability of the blood-brain barrier (BBB) whichthenalters
the transport of energy substrates through the barrier (
Leybaert, 2005
).
It is now apparent that many circulating hormones and growth factors
can cross the BBB through specific transport mechanisms that usually in-
volve their cognate receptors (
Banks, 2006
). IGF-I is one of the growth fac-
tors found to enter the brain from the circulation (
Carro, Nu˜ez, Busiguina,
& Torres-Aleman, 2000
). IGF-I is produced mainly by the liver and is an
important mediator of growth hormone actions for body growth and tissue
remodeling (
Carro, Trejo, Nunez, & Torres-Aleman, 2003
).
The serum IGF-I input to the brain is regulated by an activity-driven
process that includes changes in the permeability of the BBB to serum
IGF-I (
Nishijima et al., 2010
). IGF-1 expression is also induced by electrical
stimulation in the retina (
Morimoto et al., 2005
). Thus, electrical stimula-
tion or electrical activity may introduce circulating IGF-1 into the CNS
through the BBB or be induced. Neurons, glial cells, and vascular cells work
together to enhance neuronal activity-induced neuroprotection.
7. CONCLUSIONS: SIGNIFICANCE OF ACTIVITY-
DEPENDENT SURVIVAL
A vast amount of data has been collected on the neuronal activity-
dependent neuroprotection (
Fig. 2.1
). Much progress has been achieved
in understanding the mechanisms on how electrical activity enhances
