Biochemical and Molecular Biological Assessments of Subarachnoid Hemorrhage - Animal Models of Acute Neurological Injuries: Injury and Mechanistic Assessments - page 407

postsubarachnoid hemorrhage, such as vasospasm, but bilirubin in
experimental settings did not cause vasospasm or neurologic defi cits.
Interestingly, there is a large body of evidence demonstrating
that bilirubin has antioxidant activity. While the mechanisms of
many antioxidants is known to be an electron acceptor or trans-
porter to other electron acceptors bilirubin appeared/appears to
be a direct electron acceptor as an antioxidant. However, prior to
the year 2000, there was relatively little characterization of the
chemical changes that occurred when bilirubin was oxidized ( 25 ).
Bilirubin oxidation products (BOXes) are a relatively new family
of oxidized bilirubin that appear to be produced postsubarachnoid
hemorrhage and associated with neurologic decline and vasospasm
( 6 ). Recent mechanistic studies have found that BOXes may act in
vascular smooth muscle by manipulating phosphorylation and
dephosphorylation pathways ( 26, 27 ). These signaling pathway
changes are consistent with several of the clinical observations seen
in patients postsubarachnoid hemorrhage, thus the presence, time
course, and activity of BOXes can be employed to better evaluate the
events occurring in the subarachnoid hemorrhage patient.

2.3. Proteomics

Proteomics is a fi eld where proteins are determined and correlated
to conditions ( 28 ). Proteomic detection can detect thousands of
proteins and peptides in a sample of blood or spinal fl uid. There
are enormous problems when analyzing blood because of the large
amount of albumin, globins, hemoglobin, and immunoglobulins
in the sample. These overload many systems and can mask impor-
tant proteomic signals. It is also important to have control samples
to compare these against such that changes or differences can be
assessed. The fi eld has not yet been established long enough to
have a wide range of normal values for all the possible protein hits
that might occur. The technology is also lacking sophistication to
precisely determine subtle concentration differences, so gross pres-
ence or absence (or orders of magnitude change) tends to be
reported. It is not uncommon for a proteomic analysis on a patient
to show hundreds of differences from a baseline or control data-
base. The vast amount of data thrown at a physician or scientist
becomes unwieldy and unmanageable. The result is the research
and clinical communities are slow to adopt these methods.
However, and importantly, there are ways to simplify the proteomic
message and make it more useful.
Recent advances in microfl uidics and mass spectrometry have
enabled the latest level of technology advancement to focus pro-
teomic studies. For example, recent reports on spinal fl uid from
subarachnoid hemorrhage patients ( 29, 30 ) have found that met-
alo proteins or phosphorylated proteins can be specifi cally detected
and analyzed ( 31 ).
In 2005, the fi rst commercially available microfl udic (lab on a
chip type of technology) nano mass spectroscopy (nano-LC-ESI-MS)