Physiological Assessments of Subarachnoid Hemorrhage - Animal Models of Acute Neurological Injuries: Injury and Mechanistic Assessments - page 314

is on the intensive care unit has rendered DCI a model disease for
ischemic stroke. This notion has increasingly attracted a more gen-
eral research community with interest to study the full evolution of
ischemic stroke using sophisticated neuromonitoring technology
and perform investigator-initiated proof of concept studies on neu-
roprotectants ( 8 ). In the basic sciences, similar neuromonitoring
tools serve the purpose to expand our understanding of the clinical
conditions. The parallel use of such technologies at the bench and
the bedside provides an optimal approach for the development of
novel treatment strategies.

2. Physiological
Assessments of
the Neuronal Side

The following Chaps. 23 - 29 on the physiological assessments of SAH
start with a chapter on the process which mediates the neuronal
death in stroke for the obvious reason that all our treatment strate-
gies aim at preventing this process. Thus, it is increasingly recognized
that breakdown of the electrochemical gradients across the neuronal
membranes with prolonged intraneuronal calcium overload initiates
the cascades that eventually lead to neuronal death in stroke ( 9-14 ).
For example, toxicity of intracellular calcium was demonstrated in
cultured cortical neurons which died when treated with calcium
ionophores. The ionophores rendered the cellular membranes
permeable to calcium allowing calcium entry. The neurons underwent
apoptosis when subjected to lower and necrosis when subjected to
higher ionophore concentrations ( 14 ).
The term near-complete sustained depolarization (SD) describes
the breakdown of ion homeostasis that causes the abrupt intrac-
ellular calcium increase from about 60 nM to 25 M ( 6, 9, 15-17 ).

SD is associated with different types of synaptic dysfunction, such as
spreading depression, spreading persistent depression or non-
spreading depression of activity ( 18 ). However, the type of synaptic
dysfunction associated with SD does not determine whether or not
neurons survive a given SD. Instead, the level of sodium pump
activity and the duration of SD and, thus, the duration of the intra-
neuronal calcium surge seem to be crucial whether or not cellular
death ensues after SD. SD duration depends on the capacity of
the neurons to recruit additional sodium and calcium pump activ-
ity in order to restore the normal ionic homeostasis. Activation of
the membrane pumps is energy-dependent which explains why SD
is long-lasting and deleterious in ischemic in contrast to healthy
tissue ( 16, 19 ). The extracellular direct current (DC) shift serves as
a robust tool to assess SD duration. Experimental evidence indi-
cates that the negative extracellular DC shift associated with SD
refl ects the neuronal depolarization as it results from longitudinal
gradients of depolarization along the neurons ( 20 ).

μ