Delayed Recanalization—How Late Is Not Too Late?

Abstract

Stroke has become the second most prevalent cause of mortality in the world. Currently, the treatment of ischemic stroke is based on thrombolytic and thrombectomy therapy shortly after the ischemic event (≤ 4.5 h for thrombolytic strategies; ≤ 6 h for thrombectomy strategies). However, the majority of patients are unable to receive prompt treatment, particularly in undeveloped countries. Alternative solutions are lacking for those patients that miss the optimal window of opportunity for treatment. Recently, new developments in imaging techniques and intravascular interventional devices enable the expansion of the window of opportunity for treating stroke patients. Clinical studies have reported that delayed recanalization at 24 h, or even more than 1 month, was beneficial for some patients. However, the mechanisms of neuroprotection that underly the delayed recanalization in these ischemic stroke patients remain unclear. In this review, we will summarize the clinical studies of delayed recanalization, and organize them according to the duration of occlusion. Additionally, we will discuss the changing guidelines and possible mechanisms based on animal research, and attempt to draw conclusions and future perspectives.

Macrophage Infiltration Reduces Neurodegeneration and Improves Stroke Recovery after Delayed Recanalization in Rats

“…In support of this hypothesis, one study recently reanalyzed the data from the DEFUSE 3 study and suggested that about 20% of ischemic stroke patients with LVO who are not treated with thrombectomy had a persistent mismatch of up to 48 hours [ 20 ]. Subsequently, numerous case reports suggest a functional association between delayed blood flow restoration and neurological outcome conditional to imaging mismatch beyond 3 days from symptom onset [ 46 , 47 ]. In this study, using ischemia durations of 3 days, we validated the effect of delayed recanalization on neurological deficits and the underlying mechanisms driving these effects in a rat MCAO model.…”

Mitophagy in Cerebral Ischemia and Ischemia/Reperfusion Injury

“…Unfortunately, for many years, most AIS patients were prevented from receiving effective recanalization therapy because of a narrow therapeutic window. In recent years, a series of clinical trials have indicated that delayed recanalization may still have benefits in ischemic brains during an expanded therapeutic window, up to more than 24 h, several days, and even more than 1 month after symptom onset [Reviewed by Kang et al (2020) ].…”

Exercise‐Linked Irisin Prevents Mortality and Enhances Cognition in a Mice Model of Cerebral Ischemia by Regulating Klotho Expression

“…The incidence of ischemic stroke, which is the second cause of mortality and dementia in older individuals, is increasing annually worldwide [ 1 , 2 ]. More than 50% of stroke patients will have cognitive impairment in clinic, and about 10% of them will have dementia, which seriously affects their prognosis and quality of life [ 3 , 4 ].…”