Discussion
This case is an example of a combination widely used: aspirin and the
neuroprotective drug Cerebrolysin which can be applied in other similar
cases. It further provides evidence that the combination of Cerebrolysin
with high dose aspirin is safe and might have a synergistic effect in
the treatment of ischemic stroke.
The clinical effectiveness of Cerebrolysin has repeatedly been
demonstrated in randomized double-blind placebo-controlled multicenter
studies [1, 2]. A meta-analysis confirms previous evidence that
Cerebrolysin has a beneficial effect on early global neurological
deficits in patients with acute ischemic stroke [5]. These
underlying mechanisms of Cerebrolysin are associated with the inhibition
of calpain and consequently the stabilization of neuronal cells and with
the induction of neuronal sprouting and neurogenesis. It has also been
shown to affect a number of signaling pathways including the
phosphatidylinositol 3-kinase (PI3)/AKT pathway, the glycogen synthase
kinase 3 beta (GSK3β) pathway, the Sonic hedgehog (Shh) pathway as well
as other pathways, which are responsible for the formation and
maintenance of the blood-brain barrier integrity [4].
Antithrombotic treatment is an effective management tool for acute
ischemic stroke and early secondary prevention as it reduces the risk of
recurrent ischemic stroke with a low risk of hemorrhagic complications.
This effect is mediated by inhibition of COX-1 in the platelets
preventing their adhesion to the vascular wall, as well as by the
inhibition of acetylation of coagulation proteins which ultimately
increases the rate of fibrinolysis [7]. The neuroprotective effect
of Aspirin occurs once the blood flow in the thrombosed vessel is
restored and is due to its inhibition of COX-2 in brain tissue, a
decrease of NOTCH-1 gene expression as well as IL-6 levels, which
downregulates neuroinflammation [9,10]. Furthermore, Aspirin has
also been shown to interact with the ischemic cascade on the level of
glutamate and to significantly decrease its levels post stroke [9].
Therefore, the combined treatment of ischemic infarction with the
simultaneous use of high-dose aspirin and Cerebrolysin should act
synergistically and contribute to a more complete neurological deficit
recovery through the combined neuroprotective and neurotrophic effects
of both agents. It further provides evidence that the combination of
Cerebrolysin with high dose aspirin is safe and might have a synergistic
effect in the treatment of ischemic
stroke.
The use of Cerebrolysin in combination with high doses of aspirin may
have been the main reason for the almost complete remission of
neurological deficit in the patient with moderately severe stroke in the
right posterior cerebral artery basin, which clearly justifies the
further use of this combination in prospective studies and clinical
practice.