scholarly journals Simvastatin improves clinical scores in a rabbit multiple infarct ischemic stroke model: Synergism with a ROCK inhibitor but not the thrombolytic tissue plasminogen activator

2010 ◽  
Vol 1344 ◽  
pp. 217-225 ◽  
Author(s):  
Paul A. Lapchak ◽  
Moon Ku Han
Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Tao Peng ◽  
George L Britton ◽  
Jaroslaw Aronowski ◽  
Davide Cattano ◽  
Melvin E Klegerman ◽  
...  

BACKGROUND: Ischemic stroke is the second most common cause of death worldwide and a major cause of disability. Intravenous (iv) tissue plasminogen activator (tPA) in combination with the neuroprotective gas, xenon (Xe), is a promising strategy for ischemic stroke treatment. However, Xe delivery by inhalation may reduce oxygen uptake and tPA activity. We have developed novel Xe-containing echogenic liposomes (Xe-ELIP). In this study, we investigated the therapeutic effect of Xe-ELIP in a rat embolic stroke model. METHODS: Xe-ELIP was prepared by the pressurized-freeze method. Thrombotic strokes were induced in male Sprague-Dawley rats (n=16) by injecting a 13mm long blood clot into the middle cerebral artery (MCA). In the treatment group, tPA (10mg/kg) was infused intravenously at 2 hours after the onset occlusion. Xe-ELIP was administrated into the common carotid artery just before iv tPA. Continuous wave ultrasound (1 MHz, 50% duty cycle, 0.5 W/cm 2 ) was applied to trigger Xe release from ELIP during the 5 min of Xe-ELIP administration. Behavioral tests (limb placement, grid walking and beam walking) were conducted three days after the thrombotic stroke. Two mm-thick coronal brain sections were cut and stained with TTC to determine infarct size. RESULTS: The thrombotic stroke control group without any treatment exhibited the largest damage and infarct size (17±5% of the whole brain); tPA treatment reduced the damage and the infarct size to 5.2±0.4% of (p=0.025 vs stroke). tPA treatment in combination with Xe-ELIP further reduced the infarct size to 1.5±0.4% (p=0.05 vs tPA group) ( Fig 1a, 1b). Behavioral deficit correlated with the infarct volume reduction. Regional blood flow velocity monitored by a laser Doppler flow meter was the same in both tPA and tPA+Xe-ELIP treatment groups. CONCLUSIONS: This study has demonstrated a significant neuroprotective effect of ELIP-encapsulated xenon released by application of 1 MHz ultrasound. Xe-ELIP can be used in combination with tPA without affecting tPA thrombolytic activity.


2020 ◽  
Vol 17 ◽  
Author(s):  
Jie Chen ◽  
Fu-Liang Zhang ◽  
Shan Lv ◽  
Hang Jin ◽  
Yun Luo ◽  
...  

Objective:: Increased leukocyte count are positively associated with poor outcomes and all-cause mortality in coronary heart disease, cancer, and ischemic stroke. The role of leukocyte count in acute ischemic stroke (AIS) remains important. We aimed to investigate the association between admission leukocyte count before thrombolysis with recombinant tissue plasminogen activator (rt-PA) and 3-month outcomes in AIS patients. Methods:: This retrospective study included consecutive AIS patients who received intravenous (IV) rt-PA within 4.5 h of symptom onset between January 2016 and December 2018. We assessed outcomes including short-term hemorrhagic transformation (HT), 3-month mortality, and functional independence (modified Rankin Scale [mRS] score of 0–2 or 0–1). Results:: Among 579 patients who received IV rt-PA, 77 (13.3%) exhibited HT at 24 h, 43 (7.4%) died within 3 months, and 211 (36.4%) exhibited functional independence (mRS score: 0–2). Multivariable logistic regression revealed admission leukocyte count as an independent predictor of good and excellent outcomes at 3 months. Each 1-point increase in admission leukocyte count increased the odds of poor outcomes at 3 months by 7.6% (mRS score: 3–6, odds ratio (OR): 1.076, 95% confidence interval (CI): 1.003–1.154, p=0.041) and 7.8% (mRS score: 2–6, OR: 1.078, 95% CI: 1.006–1.154, p=0.033). Multivariable regression analysis revealed no association between HT and 3-month mortality. Admission neutrophil and lymphocyte count were not associated with 3-month functional outcomes or 3-month mortality. Conclusion:: Lower admission leukocyte count independently predicts good and excellent outcomes at 3 months in AIS patients undergoing rt-PA treatment.


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