scholarly journals Differential Temporal Evolution Patterns in Brain Temperature in Different Ischemic Tissues in a Monkey Model of Middle Cerebral Artery Occlusion

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Zhihua Sun ◽  
Jing Zhang ◽  
Yingmin Chen ◽  
Yunting Zhang ◽  
Xuejun Zhang ◽  
...  

Brain temperature is elevated in acute ischemic stroke, especially in the ischemic penumbra (IP). We attempted to investigate the dynamic evolution of brain temperature in different ischemic regions in a monkey model of middle cerebral artery occlusion. The brain temperature of different ischemic regions was measured with proton magnetic resonance spectroscopy (1H MRS), and the evolution processes of brain temperature were compared among different ischemic regions. We found that the normal (baseline) brain temperature of the monkey brain was 37.16°C. In the artery occlusion stage, the mean brain temperature of ischemic tissue was 1.16°C higher than the baseline; however, this increase was region dependent, with 1.72°C in the IP, 1.08°C in the infarct core, and 0.62°C in the oligemic region. After recanalization, the brain temperature of the infarct core showed a pattern of an initial decrease accompanied by a subsequent increase. However, the brain temperature of the IP and oligemic region showed a monotonously and slowly decreased pattern. Our study suggests thatin vivomeasurement of brain temperature could help to identify whether ischemic tissue survives.

2007 ◽  
Vol 412 (2) ◽  
pp. 114-117 ◽  
Author(s):  
John C. Ashton ◽  
Rosanna M.A. Rahman ◽  
Shiva M. Nair ◽  
Brad A. Sutherland ◽  
Michelle Glass ◽  
...  

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Alexander Akhmedov ◽  
Remo D Spescha ◽  
Francesco Paneni ◽  
Giovani G Camici ◽  
Thomas F Luescher

Background— Stroke is one of the most common causes of death and long term disability worldwide primarily affecting the elderly population. Lectin-like oxidized LDL receptor 1 (LOX-1) is the receptor for oxidized LDL identified in endothelial cells. Binding of OxLDL to LOX-1 induces several cellular events in endothelial cells, such as activation of transcription factor NF-kB, upregulation of MCP-1, and reduction in intracellular NO. Accumulating evidence suggests that LOX-1 is involved in endothelial dysfunction, inflammation, atherogenesis, myocardial infarction, and intimal thickening after balloon catheter injury. Interestingly, a recent study demonstrated that acetylsalicylic acid (aspirin), which could prevent ischemic stroke, inhibited Ox-LDL-mediated LOX-1 expression in human coronary endothelial cells. The expression of LOX-1 was increased at a transient ischemic core site in the rat middle cerebral artery occlusion model. These data suggest that LOX-1 expression induces atherosclerosis in the brain and is the precipitating cause of ischemic stroke. Therefore, the goal of the present study was to investigate the role of endothelial LOX-1 in stroke using experimental mouse model. Methods and Results— 12-week-old male LOX-1TG generated recently in our group and wild-type (WT) mice were applied for a transient middle cerebral artery occlusion (MCAO) model to induce ischemia/reperfusion (I/R) brain injury. LOX-1TG mice developed 24h post-MCAO significantly larger infarcts in the brain compared to WT (81.51±8.84 vs. 46.41±10.13, n=7, p < 0.05) as assessed morphologically using Triphenyltetrazolium chloride (TTC) staining. Moreover, LOX-1TG showed higher neurological deficit in RotaRod (35.57±8.92 vs. 66.14±10.63, n=7, p < 0.05) and Bederson tests (2.22±0.14 vs. 1.25±0.30, n=9-12, p < 0.05) - two experimental physiological tests for neurological function. Conclusions— Thus, our data suggest that LOX-1 plays a critical role in the ischemic stroke when expressed at unphysiological levels. Such LOX-1 -associated phenotype could be due to the endothelial dysfunction. Therefore, LOX-1 may represent novel therapeutic targets for preventing ischemic stroke.


2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Jing Zhang ◽  
Ying-min Chen ◽  
Yun-ting Zhang

Objective. To investigate the value of BOLD-based reversible transverse relaxation rate (R2′) MRI in detecting ischemic penumbra (IP) in a monkey model of reversible middle cerebral artery occlusion (MCAO) and time evolution of relative R2′ (rR2′) in infarcted core, IP, and oligemia.Materials and Methods. 6 monkeys were used to make MCAO by the microcatheter method. MR scans were performed at 0 h (1 h after MCAO), 1 h, 3 h, 6 h, 12 h, 24 h, and 48 h after reperfusion. R2′ was calculated using quantitative T2 and T2∗maps. Ischemic area was subdivided into infracted core, IP and oligemia. rR2′ was calculated respectively.Results. Reversible MCAO model for 4/6 monkeys was made successfully. rR2′ values were significantly different at each time point, being highest in oligemia followed by IP and infarcted core (). With reperfusion time evolution, rR2′ in infarcted core showed a decreased trend: sharply decreased within 6 hours and maintained at 0 during 6–48 hours (). rR2′ values in IP and oligemia showed similar increased trend: sharply increased within 6 hours, maintained a plateau during 6–24 hours, and slightly increased until 48 hours.Conclusion. BOLD-based R2′ MRI can be used to describe changes of cerebral oxygen extract in acute ischemic stroke, and it can provide additional information in detecting IP. The time evolution rR2′ in infarcted core, IP, and oligemia is in accordance with the underlying pathophysiology.


Molecules ◽  
2018 ◽  
Vol 23 (7) ◽  
pp. 1747 ◽  
Author(s):  
Nan Li ◽  
Lingling Feng ◽  
Yujun Tan ◽  
Yan Xiang ◽  
Ruoqi Zhang ◽  
...  

The dry root of Scutellaria baicalensis, has traditionally been applied in the treatment of cerebral ischemia in Chinese clinics. Baicalin (BA) is considered the key ingredient in it for the brain protection effects. The bioavailability of BA is very low because of its poor lipid and water solubility, which limits the therapeutic effects and clinical application. The aim of the present study was to develop a novel BA-loaded liposome (BA-LP) formulation to improve the drug lipophilicity and further to enhance the drug-concentration in the brain tissues. This study is also designed to investigate the pharmacokinetics of BA in the pathological conditions of stroke and evaluate the pharmacokinetic differences of BA caused by stroke after intravenous administration with BA and BA-LP. In this study, the novel BA-LP prepared in early stage were characterized by morphology, size, zeta potential, encapsulation rate and the in vitro release. The pharmacokinetics and biodistribution of BA and BA-LP were investigated by intravenous administration in rats with middle cerebral artery occlusion (MCAO) model and normal group respectively. BA-LP had a mean particle size of 160–190 nm, zeta potential of −5.7 mV, and encapsulation efficiency of 42 ± 1%. The BA-LP showed a sustained-release behavior, the in vitro drug-release kinetic model of BA-LP fit well with the biphasic dynamic model equation: Q = 1 − (60.12e0.56t − 59.08e0.0014t). Pharmacokinetic behavior in MCAO rats is not consistent with that of normal rats. The middle cerebral artery occlusion rats got higher Cmax and AUC0–t, which were about 1.5–2 times to normal rats both in BA and liposome groups. In addition, it got especially higher distribution in brain, while BA were not detected in brain tissues on normal rats. The Cmax and AUC0–t values were significantly greater with liposome than BA on both normal and MCAO rats. The tissue distribution behavior was significantly altered in the case of liposome administrated in comparison with BA, which the concentrations in the heart, liver, spleen, lungs and brain were all increased after administrated liposome, but decreased in kidneys. The TI values showed that the target of liposome was improved especially to heart, spleen and brain, and the brain’s target was higher in striatum and cerebellum. In conclusion, BA-LP might be a potential drug delivery system to improve the therapeutic efficacy of BA. In addition, these results also suggest that the pathological damages of ischemia-reperfusion have a significant impact on the pharmacokinetic traits of BA.


2010 ◽  
Vol 13 (4) ◽  
pp. 607 ◽  
Author(s):  
Dorothee Lang ◽  
Christian Ude ◽  
Mario Wurglics ◽  
Manfred Schubert-Zsilavecz ◽  
Jochen Klein

ABSTRACT. Purpose. Bilobalide is an active constituent of Ginkgo biloba and has shown neuroprotective effects in mice with cerebral ischemia. In the present study, we investigated brain permeability of bilobalide (i) in healthy mice and (ii) in mice before or after stroke. Methods. We have used in vivo microdialysis and LC-MS to estimate extracellular levels of bilobalide. 10 mg/kg of bilobalide was given by i.p. injection to control mice, and 60 minutes before and after middle cerebral artery occlusion (MCAO). Results. Bilobalide was already detectable in brain striatal microdialysates 10 min after i.p. administration and reached maximum levels (19 ng/mL, corresponding to 0.92 µM) after 40 min. Maximum plasma bilobalide levels were 5.9 µM. After an ischemic insult, the drug could be dialysed with similar efficiency as in control mice indicating slow elimination from the ischemic brain. When the drug was given after MCAO, availability in the brain was low, but measurable, at approx. 10% of control values. Conclusions. Our data demonstrate that bilobalide easily crosses the blood brain barrier and reaches extracellular concentrations in the brain that allow efficient interaction with target molecules such as neurotransmitter receptors. Availability of the drug in ischemic tissue is high when given before ischemia, but severely limited after MCAO.


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