1.Introduction
Acute ischemic stroke (AIS) is the most common type of stroke. It has
the characteristics of high morbidity, high mortality, and high
disability, which seriously endangers the health and life of patients.
(1) Effective treatment after AIS will directly affect the prognosis of
patients. (1)
The devastating, often crippling aftermath of stroke makes it second
only to cardiac ischemia as a cause of death worldwide. Therapy for AIS
centers first on rapid revascularization of arterial territories, with
additional focus on managing blood pressure and cerebral
edema.(2)Revascularization is currently achieved by the intravenous
administration of tissue plasminogen activator (tPA) and intravascular
therapy. However, the benefit of tPA is highly time-dependent,
considering that pooled analysis has documented loss of benefit beyond
4.5 h from onset of symptoms.(2-4). Despite numerous clinical trials
conducted to salvage cells from death, no significant breakthrough has
been made to improve the outcome of stroke patients.(2, 5, 6)
Cerebral ischemia-induced cell death swiftly activates the immune system
and initiates inflammation within the brain.(7-11)In an early phase,
these immune responses appear to exacerbate neurovascular dysfunction by
promoting thrombus formation, and accumulation of blood components in
the cerebral microvasculature.(11-13)These changes subsequently
exacerbate the ischemic cascade catalyzing neural cell death in the
penumbra, resulting in the extension of infarction, which potentially
limits the efficacy of pharmacologic or mechanical reperfusion. (11,
14-16)
Fingolimod
is a sphingosine analog that acts on sphingosine-1-phosphate
receptors(S1PR). It was approved by the US. Food and Drug Administration
in 2010 as the first oral disease-modifying therapy for the
relapsing-remitting form of multiple sclerosis (MS). (17, 18) Fingolimod
inhibits the egress of lymphocytes from lymph nodes and limits their
recirculation.(18, 19) Additional effects on the integrity of the
blood-brain barrier(BBB) and direct action on neurons and glia that bear
sphingosine-1-phosphate receptor may also contribute to its beneficial
attributes in MS.(18, 20-22) Recently, the safety and efficacy of
fingolimod in both patients with intracerebral hemorrhage and patients
with AIS have been investigated in proof-of-concept trials.(2, 18)
Fingolimod limited the expansion
of infarct volume and ameliorated hemorrhagic transformation in patients
with acute ischemic stroke who received intravenous alteplase within 4.5
hours after stroke onset(11, 18), Meanwhile, in patients with acute
anterior circulation occlusion who are >4.5 hours after
disease onset, fingolimod significantly improved the clinical outcome,
reduced secondary lesion growth, and decreased microvascular
permeability. (18) In this
systematic review, we performed a meta-analysis to evaluate the efficacy
and safety of fingolimod for acute ischemic stroke.