Biochemical and Molecular Biological Assessments of Subarachnoid Hemorrhage - Animal Models of Acute Neurological Injuries: Injury and Mechanistic Assessments - page 406

oxygen that can often occur by the addition of an extra electron.
However, that molecule will not want to “share” that electron in
an ionic bond, it will tend to form covalent bonds, which means
that new molecules are formed. Reactive oxygen species are not
necessarily ionized, but are oxygen containing molecules that are
chemically active, such as hydrogen peroxide. These molecules as
representatives for their molecular families can chemically modify
numerous molecules susceptible to their nucleophilic attack. The
result is a host of covalently modifi ed molecules.
Lipid oxidations are a common occurrence when there is
oxidative stress because the brain and all cell membranes contain
lipids that can be oxidized. Typically unsaturated lipids are more
susceptible to oxidation because their double bonds produce an
electron cloud in the pi orbital that forms a partial negative charge,
the constitutive positive charge caused by electron withdraw is
prone to covalent modifi cation from negatively charged oxygen-
free radicals. The result is that poly unsaturated fatty acids, such as
arachidonic acid, are covalently modifi ed to produce compounds,
such as the HETEs and EETs ( 2-4 ). The observation of HETEs
and EETs in blood and spinal fl uid of subarachnoid hemorrhage
patients is indicative of lipid oxidation. The type of lipids oxidized
contain information concerning the pathology/damage being
done and a growing body of evidence suggests that the products of
such oxidations may be biologically active and contribute to
complications postsubarachnoid hemorrhage ( 2, 5-8 ).
Lipids, even oxidized lipids, such as HETEs and EETs, are
good candidates for markers that can be assessed in the spinal fl uid
as well as blood markers. Further several HETEs and EETs are
known to activate the immune system, so concomitant activation
of infl ammatory markers is expected ( 9-11 ). A lack of apparent
response may indicate a threshold for HETEs and/or EETs or that
the duration of their levels may be insuffi cient for an immune
response. Thus, this introduces an important component to the
ethos or theme for this part of the discussion. One marker being
evaluated could impact on other markers and thus a physician
learning to evaluate spinal fl uid and blood markers will need to
learn how they interact. Similar to when physicians are learned to
read pH markers in a CBC and have an understanding of renal
versus respiratory compensation for pH, the physician will need to
understand how markers interact as well.

Our lab has been studying the structure, time course, and biological
activity of blood products in the spinal fl uid of the subarachnoid
hemorrhage patient ( 1, 6, 7, 12-18 ). Historically, bilirubin was
implicated in the pathogenesis seen in subarachnoid hemorrhage
patients and complications seen therein ( 19-24 ), but the cause and
effect role for bilirubin was unclear. The time course for bilirubin
appearance in the spinal fl uid was concomitant with complications

2.2. Blood Products