Statins for neuroprotection in spontaneous intracerebral hemorrhage

Abstract

Statins, a common drug class for treatment of dyslipidemia, may be neuroprotective for spontaneous intracerebral hemorrhage (ICH) by targeting secondary brain injury pathways in the surrounding brain parenchyma. Statin-mediated neuroprotection may stem from downregulation of mevalonate and its derivatives, targeting key cell signaling pathways that control proliferation, adhesion, migration, cytokine production, and reactive oxygen species generation. Preclinical studies have consistently demonstrated the neuroprotective and recovery enhancement effects of statins, including improved neurologic function, reduced cerebral edema, increased angiogenesis and neurogenesis, accelerated hematoma clearance, and decreased inflammatory cell infiltration. Retrospective clinical studies have reported reduced perihematomal edema, lower mortality rates, and improved functional outcomes in patients who were taking statins before ICH. Several clinical studies have also observed lower mortality rates and improved functional outcomes in patients who were continued or initiated on statins after ICH. Subgroup analysis of a previous randomized trial has raised concerns of a potentially elevated risk of recurrent ICH in patients with previous hemorrhagic stroke who are administered statins. However, most statin trials failed to show an association between statin use and increased hemorrhagic stroke risk. Variable statin dosing, statin use in the pre-ICH setting, and selection biases have limited rigorous investigation of the effects of statins on post-ICH outcomes. Future prospective trials are needed to investigate the association between statin use and outcomes in ICH.

MicroRNAs hsa-miR-618 and hsa-miR-297 Might Modulate the Pleiotropic Effects Exerted by Statins in Endothelial Cells Through the Inhibition of ROCK2 Kinase: in-silico Approach

“…Several studies in animal models of spontaneous intracerebral hemorrhage that have been treated with statins have improved neurological function, reduced cerebral edema effects, increasing angiogenesis, and neurogenesis, and have decreased the infiltration of inflammatory cells. This supports the possible neuroprotective effects of statins (55)(56)(57).…”

Predicting mortality from intracranial hemorrhage in patients who undergo allogeneic hematopoietic stem cell transplantation

“…First, our findings indicate that it is reasonable to manage the low-and intermediate-risk patients according to the current AHA/ASA guidelines and a nihilistic clinical response should never be taken, although ICH on top of allo-HSCT has traditionally been considered fatal 3 . Second, the dismal prognosis of high-risk patients shows that the treatments currently in use are not sufficient for them and novel treatments for ICH may be considered, which include minimal invasive surgery (MIS), novel hemostatic agents and neuroprotective agents 36,[58][59][60][61][62][63][64][65][66][67][68][69] (Supplemental Table 4). The DCA results also showed that it would be beneficial to use the LAWS score to aid clinicians in selecting patients at higher risk of early mortality and in more urgent need of novel ICH treatments other than the standard ones [28][29][30] .…”

A Retrospective Study on Statins and Post-stroke Patients: What About Functional Outcome and Follow-Up in a Stroke Rehabilitation Cohort?

“…In mice with embolic stroke, low atorvastatin doses are able to induce the expression of vascular endothelial growth factor (VEGF), thus promoting neovascularization, and improve neurological function by enhancing synaptogenesis and proliferation of neural progenitor cells ( 10 ). Neuroprotective effects of statins, including antioxidative, anti-inflammatory, angiogenic, neurogenic, and antiapoptotic properties, have also been demonstrated in animals with hemorrhagic stroke ( 37 ). All these findings led to hypothesized that statin administration may positively influence cerebral repair after injury acting on neurogenesis and angiogenesis ( 7 , 9 , 10 , 16 , 36 ).…”