Physiological Assessments of Subarachnoid Hemorrhage - Animal Models of Acute Neurological Injuries: Injury and Mechanistic Assessments - page 316

is a signifi cant component of DCI but proximal vasospasm alone
does not provide the explanation of the problem.
The phenomenon of spreading ischemia probably deserves
special attention since it is complex as it results from a vicious cycle
between neuronal and vascular dysfunction and seems to play
a role in the early and delayed brain damage after SAH ( 8, 18 ).
As mentioned above, SD not only occurs under ischemic condi-
tions but can also be ignited in relatively healthy, normally perfused
cortex. Under this condition, SD is a short-lasting and harmless
event. However, SD causes a fall of tissue ATP by 50% even in
healthy, normally perfused tissue since sodium and calcium pumps
are immediately activated to restore the normal ion homeostasis
( 32 ). To match this increased energy demand, regional vasodilatation
and blood fl ow increase are coupled to SD under normal conditions
(normal hemodynamic response) ( 33 ). However, in the presence
of different pathological conditions, such as the presence of eryth-
rocyte degradation products in the subarachnoid space, the vascular
reactivity changes, thus, severe microvascular spasm is coupled to SD
(inverse hemodynamic response) ( 26 ). This produces a mismatch
between energy demand and delivery which prevents the recovery
from SD, prolongs the deleterious intraneuronal calcium surge as
well as the negative extracellular DC shift and maintains the neu-
ronal/astroglial release of vasoconstrictors. Thus, a vicious cycle is
established that eventually leads to widespread focal necrosis
( 17, 34, 35 ). By defi nition, the term spreading ischemia describes
the SD-induced perfusion defi cit when it leads to a prolonged
negative extracellular DC shift ( 26 ). Thus, the combination of
DC-electrocorticography with a method to measure regional cere-
bral blood fl ow is needed to record spreading ischemia.
4. Outlook
The last decade has witnessed a paradigmatic change on the neuronal
and vascular side of the pathogenesis of brain damage following
SAH. Direct clinical evidence now exists for a number of phenomena
in addition to the traditional player, proximal vasospasm. Among
those are SD and spreading ischemia in the early and delayed period
after SAH (demonstrated using subdural opto-electrodes for
electrocorticography and laser-Doppler fl owmetry) ( 6, 8 ) as well
as microthrombosis (demonstrated in autoptic specimens) ( 29 ).
Moreover, blood-brain barrier (BBB) disruption should be men-
tioned here although it has been known for a long time to follow
SAH ( 36 ). However, experimental evidence has recently suggested
that BBB disruption of itself can induce secondary neuronal degen-
eration and epileptogenesis ( 37, 38 ). This should boost attention
to its specifi c role in the pathogenesis of brain damage after SAH.