The cutting edge: apoptosis and therapeutic opportunity - Artificial Cells, Cell Engineering and Therapy - page 121

several ways, including the alteration of the mitochondrial permeability transi-
tion pores (mPTP), allowing for the release of pro-apoptotic proteins, promoting
release of cytochrome c from the inner mitochondrial membrane, as well as the
activation of transcription factors of various pro- and anti-apoptotic factors
(Nomura et al., 2000).
Numerous other pathways have also been identified as leading to apoptosis in
post-mitotic cells such as receptor mediated, as well as caspase dependent and
independent; however in cases of neurodegenerative diseases such as stroke, an
increase in ROS after injury is the primary trigger of neuronal death because of
the brain's strong susceptibility to damage from oxidative stress. Specifically,
there are several reasons for the detrimental effects of ROS on the brain:
primarily, the brain makes up a small percentage of the overall body weight
(2%) but consumes nearly 20% of oxygen entering the body. Secondly, the brain
contains relatively low levels of antioxidant species while levels of lipids
sensitive to oxidation remain high. In addition, some regions are found to be rich
in iron, which can catalyze formation of free radicals (Cherubini et al., 2005).
5.4 Stroke management
5.4.1 Stroke management: current treatment strategies
Presently, treatment of stroke involves several drug therapies including anti-
coagulants such as warfarin and thrombolytic recombinant tissue plasminogen
activator (r-TPA) (Margaill et al., 2005). Anticoagulant drugs therapies are used
to treat stroke or cardiac arrest patients; however this is more of a preventive
measure. For example, acetylsalicylic acid (ASA) and warfarin work by
decreasing the ability of clot-forming components (platelet cells in the blood)
from sticking together, thus limiting the possibility of clot formation.
Thrombolytic drugs are used in cases of ischemic stroke; that is when a clot is
blocking the blood supply to a particular part of the brain. In these cases, this
therapy must be applied within 3 h of stroke onset, which is severely limiting
since many patients are unaware of their symptoms and take hours or days to
seek treatment. However, when taken within the correct time period this therapy
can successfully allow reperfusion of the oxygen-deprived region. In some
cases, if the affected part of the brain is small enough, rTPA can lead to
complete reversal of symptoms. Unfortunately, it is not uncommon for patients
to experience weakness or paralysis in various body parts as well as difficulty in
speaking owing to irreversible damage to the core and penumbra regions of the
brain, discussed above.
5.4.2 Stroke management: recent progress
Although reperfusion can restore proper blood flow to affected regions in the
brain, as previously discussed, a consequence to this treatment is the generation