Figure 4 Molecular process of neuronal ischaemia. (Colledge, Walker and Ralston., 2010, p. 1182)
Available treatments for stroke
Patients, who have already endured a stroke, are at high risk of stroke recurrence. The medicines used for treatment of ischemic stroke at the moment are: thrombolytics (alteplase), anti-platelet medication (Aspirin), anticoagulants (Warfarin) and mechanical thrombectomy.
Aspirin reduces the risk of stroke in 23% of the cases (Diener., 2004). As soon as ischaemic stroke has been recognized, patients are given aspirin in sensible doses (160-350 mg/d), improving survival and reducing the risk of recurring strokes.
The benefits of aspirin in stroke patients are due to its ability to suppress prostaglandin and thromboxane synthesis, by irreversibly inactivating prostaglandin-endoperoxide synthase(PTGS) enzyme. Platelets do not possess DNA and therefore, are unable to produce more PTGS, thus aspirin inhibits platelet aggregation, preventing blood clot formation (Figure 5).
Figure 5 The mechanism of aspirin inhibiting ptgs enzyme (Novara., 2013)
However, haemorrhagic strokes cannot be treated or prevented with aspirin, as it can cause excess bleeding, especially in high doses or during long-term use and increase the risk of another haemorrhagic stroke.
Aspirin is cost-effective and widely available and can be used in combination with other anti-platelet agents, such as dipyridamole to prevent strokes. For treatment of embolic strokes in high risk patients, aspirin is not sufficient and stronger anti-coagulants, such as warfarin are used.
Thrombolysis medications, such as alteplase, a recombinant tissue plasminogen activator (rt-PA), work by binding to fibrin rich haemostatic clots, via the fibronectin type 1 domain and the Kringle 2 domain. Plasminogen is the inactive precursor of plasmin and is activated by rt-PA. The protease domain in rt-PA then cleaves the Arg561 - Val562 peptide bond in plasminogen to create plasmin. Plasmin is a serine protease and can cleave the haemostatic clot, consisting of polymerized fibrin and platelets by proteolytic digestion. Therefore, rt-PA mediates recanalization of the congested vessels (Figure 6).
Figure 6 Mechanism of t-pa action, (Genentech, 2014)
Rt-PA is contraindicated in hemorrhagic stroke and older ischaemic stroke patients with mild or resolving symptoms and thrombophilia (hypercoagulability of blood, which increases the risk of thrombosis), as it increases the risk of intracranial bleeding.
Thrombectomy is the surgical removal of the blood clot, mechanically recanalising the obstructed vessels. It is used in patients unsuitable for rt-PA therapy or in combinations with it. It can be proximal and distal (Figure 7). Proximal thrombectomy involves the placement of an aspiration catheter at the proximal site of the thrombus, followed by manual suction. Then, manual aspiration is applied and the catheter is retrieved under constant negative pressure. Distal thrombectomy is more technically challenging. To deliver the device distally to the thrombus, a microcatheter is passed at the occlusion site. To avoid thromboembolic problems, a balloon guide catheter is placed in the cervical internal cerebral artery and aspiration during device retrieval is recommended for most devices.
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Figure
7
Thrombectomy illustrated.
(Mordasini et al.,
2012)
A
- Catheter aspiration thrombectomy
B
- Mechanical thrombectomy devices
C
- Proximal embolic protection devices
D
and E - Distal embolic protection devices
Stem cells are unspecialized cells competent of self-renewal through mitosis, even after being inactive for a long time. Stem cells are able to differentiate into organ or tissue specific cells and adopt their functions. Activation of stem cells relies on physiological environment or experimental conditions used for stem cell culturing. These characteristics allow stem cell differentiation from other cell types.
Types of stem cells include: embryonic stem cells, adult stem cells and induced pluripotent stem cells