Interrupted intracarotid artery cold saline infusion as an alternative method for neuroprotection after ischemic stroke

Abstract

<jats:sec> <jats:title>Object</jats:title> <jats:p>Intracarotid artery cold saline infusion (ICSI) is an effective method for protecting brain tissue, but its use is limited because of undesirable secondary effects, such as severe decreases in hematocrit levels, as well as its relatively brief duration. In this study, the authors describe and investigate the effects of a novel ICSI pattern (interrupted ICSI) relative to the traditional method (uninterrupted ICSI).</jats:p></jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Ischemic strokes were induced in 85 male Sprague-Dawley rats by occluding the middle cerebral artery for 3 hours using an intraluminal filament. Uninterrupted infusion groups received an infusion at 15 ml/hour for 30 minutes continuously. The same infusion speed was used in the interrupted infusion groups, but the whole duration was divided into trisections, and there was a 20-minute interval without infusion between sections. Forty-eight hours after reperfusion, H &amp; E and silver nitrate staining were utilized for morphological assessment. Infarct sizes and brain water contents were determined using H &amp; E staining and the dry-wet weight method, respectively. Levels of neuron-specific enolase (NSE), S100β protein, and matrix metalloproteinase 9 (MMP-9) in the serum were determined using enzyme-linked immunosorbent assay. Neurological deficits were also evaluated.</jats:p></jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Histology showed that interrupted ICSI did not affect neurons or fibers in rat brains, which suggests that this method is safe for brain tissues with ischemia. The duration of hypothermia induced by interrupted ICSI was longer than that induced via the traditional method, and the decrease in hematocrit levels was less pronounced. There were no differences in infarct size or brain water content between uninterrupted and interrupted ICSI groups, but neuron-specific enolase and matrix metalloproteinase 9 serum levels were more reduced after interrupted ICSI than after the traditional method.</jats:p></jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Interrupted ICSI is a safe method. Compared with traditional ICSI, the interrupted method has a longer duration of hypothermia and less effect on hematocrit and offers more potentially improved neuroprotection, thereby making it more attractive as an infusion technique in the clinic.</jats:p></jats:sec>

Intermittent Hypothermia Is Neuroprotective in an in vitro Model of Ischemic Stroke

“…Continuous ICSI requires a large volume of cold saline to achieve a therapeutic hypothermia and thus generates significant side effects such as hematocrit dilution. Intermittent ICSI can significantly reduce the volume of cold saline; using a rat model of focal cerebral ischemia, intermittent ICSI could lower down brain temperature effectively, resulting in prolonged continuous hypothermia and greater neuroprotection, while minimizing its impact on hematocrit comparing to continuous ICSI 6. Of note, intermittent ICSI could solve the problem of infusion volume; however it may produce re-warming complications to stroke patients.…”

TFP5 peptide, derived from CDK5-activating cofactor p35, provides neuroprotection in early-stage of adult ischemic stroke

“…A modified intraluminal filament model was used to induce MCAO as previously described3839. After 2 h of MCAO, reperfusion was established by retracting the filament.…”

“…The sections were photographed with a digital camera after 2 h, and the infarct size was measured by ImageJ software (National Institutes of Health, US). To eliminate the contribution of post-ischemic edema to the volume of injury, infarct size was corrected as described previously3839. The infarct size (%) was calculated as [(volume of the left hemisphere - noninfarct volume of the right hemisphere)/volume of the left hemisphere] × 100%.…”

Hypothermia in Stroke Therapy: Systemic versus Local Application

“…This is consistent with other reports on the topic, which suggests that Egr-1 is the key component modulated by TH. However, information regarding early cellular response to ischemia and hypothermia has largely been conlicting, leaving the speciics of its involvement unclear [38] and inconsistent [31,32].…”

“…Pre-reperfusion LEVI has since been shown to reduce infarct volumes by 75 [29] to 90% [30] and signiicantly conserve motor function both hours and weeks after stroke [29,30]. Post-reperfusion LEVI has also been considered in some studies, in which a catheter was introduced into the internal carotid artery after blood low to the ischemic territory had been reestablished [31,32]. Signiicant improvements in both infarct volume and functional recovery were observed in every post-reperfusion LEVI trial tested, but these improvements were not as pronounced as those from pre-reperfusion LEVI.…”