*2.3. Current Treatment Options for Ischemic Stroke*

Treating ischemic stroke is to restore blood flow to the brain as soon as possible, and reperfusion is a major tool to bring the blood back to the brain. The clinical methods include intravenous administration of tissue plasminogen activator (tPA) and mechanical thrombectomy (MT) [34]. Tissue plasminogen activator (tPA) is the gold standard treatment for ischemic stroke. The treatment window using tPA is in 4.5 h when patients show the stroke symptom, and the outcomes dramatically decrease beyond 4.5 h [35]. However, tPA treatment may potentially cause the intracerebral hemorrhage and lead to more mortality [36]. When patients appear with a large artery occlusion (the clot burden is high) or tPA treatment is beyond the best time window, the MT surgery is an alternative strategy to treat ischemic stroke. In MT surgery, a microcatheter is inserted to clotting blood vessels to remove the clots. The treatment procedure for stroke patients is summarized in Figure 2.

**Figure 2.** The procedure to treat stroke patients. CT: computed tomography; MRI: magnetic resonance imaging; LVO: large vessel occlusion; IV-tPA: intravenous injection of trans-plasminogen activator; ICU: intensive care unit; NIHSS: National Institutes of Health Stroke Scale; Y: yes; N: no.

Except for the reperfusion, supportive care is also very important. For example, 25% of patients may show neurological deficiency in 24–48 h, and care is needed to prevent further brain damage [37]. Although stroke and its pathogenesis have been investigated for many years, there are no pharmacological agents available in clinic to effectively treat ischemic stroke [38,39].

There are several drugs that have been tested to target inflammatory pathways in ischemic stroke. NXY-059 is a scavenger of free radicals and shows the neuroprotective effect in a pre-clinical stroke model [40]. However, NXY-059 was less effective in Stroke–Acute Ischemic NXY Treatment II (SAINT II) trial [41]. The failure may be due to the high water solubility of NXY-059 that has low permeability to BBB. Therefore, developing new drug delivery approaches are needed to solve the current issues on treating ischemic stroke.
