Vasileios-Arsenios Lioutas, MD

IV tPA is the main weapon in our armamentarium for acute stroke treatment. Its beneficial effect comes at the cost of symptomatic intracranial hemorrhage with significant impact on mortality and functional outcome for the affected patients, especially with delayed administration. An agent that would attenuate the hemorrhage risk without interfering with the fibrinolytic activity would be ideal as adjunctive therapy.

In this interesting proof of concept study, Amarenco et al investigated the effect of HDL administered intravenously along with tPA in ischemic stroke in rats. Two different models of middle cerebral artery occlusion characterized by high incidence of post tPA parenchymal hematoma formation and mortality. HDLs were chosen due to their suggested pleiotropic endothelial protective effects (e.g. anti-oxidant, anti-inflammatory).

Infarct volume and 24-hour mortality were significantly decreased and the incidence of parenchymal hemorrhage was decreased by 90% in the HDL treated group compared to tPA alone. Moreover, both in vivo and in vitro data unequivocally showed a beneficial effect of HDL in blood-brain barrier integrity, without attenuation of tPA’s fibrinolytic activity in vitro or ex vivo.

These are undeniably impressive results that offer support to the original hypothesis that HDLs have a neuro- and vasculo- protective effect. Several points need to be underlined: HDLs comprise a structurally and functionally heterogeneous group of lipoproteins. Their in vivo function is quite complex, as they very likely act as transporters of other molecules that render their biological action acutely efficacious. Their composition and functionality are altered in the context of disease processes. Therefore, HDLs derived from plasma of healthy individuals are very likely biologically different compared to those from patients with metabolic syndrome and recombinant HDLs created in the lab. 

The results of this study are promising, but limited to short term outcome and need to be replicated by further experiments. First and foremost, it remains to be seen whether HDLs will have the fate of so many other neuroprotective agents, which failed the ultimate test of human stroke clinical trials despite auspicious results in preclinical studies.