Biology Reference
In-Depth Information
changes in brain activity and energy metabolism. Any alterations in
this neurovascular coupling in the diseased brain will greatly alter
brain function and neuronal survival. Monitoring of rCBF changes in
animal models of aneurysmal subarachnoid hemorrhage (SAH) is of
great importance to elucidate the interrelation between occurrence
of disturbed coupling and tissue damage and to determine the under-
lying pathophysiology. In fact, the study of the pathological condi-
tions following SAH yielded the original discovery that disturbed
neurovascular coupling of itself can be detrimental to the tissue (
2
).
Near-complete sustained depolarizations (SDs) occur on the
neuronal side of this process. SDs are characterized by the break-
down of the brain's ion homeostasis and were shown to occur fre-
quently in SAH animal models of the initial (
3, 4
) as well as the
delayed time period (
2, 5
). Moreover, SDs were observed in abun-
dance in patients with SAH (
6
). As explained in Chaps.
28
and
29
,
SD establishes and maintains the intraneuronal calcium surge that
initiates the cascades leading to neuronal death if the calcium surge
exceeds a certain time limit (
7, 8
).
Even under resting conditions, the main expenditure of the
brain's energy budget is related to ATP consumption by the sodium
pumps to maintain the normal ion gradients across the neuronal
membranes and, thus, to prevent the intracellular calcium surge.
Recovery from SD requires massive additional energy-dependent
recruitment of sodium and calcium pump activity to restore the
normal ion homeostasis. Thus, even in healthy, normally perfused
tissue where SD is harmless and recovery from SD is achieved
within 1 or 2 min, ATP falls by about 50% (
9
). In response to the
increase of energy demand, vasodilatation and increase of rCBF are
coupled to SD. Thus, oxygen and glucose availability increases
(
10, 11
). The opposite of the normal neurovascular response to
SD occurs when there is dysfunction of the microvasculature, such
as after SAH. Inverse neurovascular coupling was discovered and
extensively studied in an animal model for the conditions following
SAH and has been recently found in patients with SAH (
2, 5,
12-14
). With inverse coupling, severe microvascular spasm is cou-
pled to SD instead of vasodilatation. This results in spreading isch-
emia. The perfusion defi cit in turn causes prolongation of the
neuronal depolarization and prolongation of the detrimental intra-
neuronal calcium surge. Thereby, a relatively harmless SD becomes
a deleterious wave that results in widespread focal necrosis (
15
).
2. Material
and Instruments
Investigations on the relationship between changes in rCBF and
neuronal activity and on the interrelation between SD and spread-
ing ischemia are mostly done in paradigms which use open or
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