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.