Objective : The authors investigate the spatial characteristics of apoptotic genes expressed around the focal cerebral infarction, and attempted to explain the penumbra with them. Methods : A delayed focal cerebral infarction was created in twelve adult Sprague-Dawley rats. We performed the immunohistochemical staining for the apoptosis, bcl-2 and p53 proteins and measured the local cerebral blood flow [CBF] at the infarction core area and peri-infarct area pre- and intra-operatively. The peri-infarct area was divided into six sectors by distance from the infarction border. Results : The size [$mm^2$] of apoptosis, bcl-2, and p53 areas were $3.1{\pm}1.2$, $4.7{\pm}2.1$, and $6.8{\pm}2.4$, respectively. Apoptosis, bcl-2 or p53 positive cells were concentrated at the peri-infarct area adjacent to the infarction core. Their numbers reduced peripherally, which was inversely proportional to the local CBF. The p53 area seems to overlap with and larger than the ischemic penumbra. Conclusion : The p53 positive area provides a substitutive method defining the penumbra under the molecular base of knowledge.
Journal of Physiology & Pathology in Korean Medicine
/
v.21
no.3
/
pp.741-747
/
2007
This study evaluated neuroprotective effects of Yanggyuksanhwa-tang (YST), which have been known to be efficacy in the treatment of the stroke and diabetes. on focal cerebral ischemia of diabetic rats. On primary experiment, diabetic condition in rats was induced by streptozotocin injection, then, focal cerebral ischemia was induced by the middle cerebral artery occlusion (MCAO) under the diabetic condition. Then neuroprotective effect of YST was observed with changes of infarct size and volume, expressions of c-Fos, Bax, and hypoxia inducible factor (HIF)-1${\alpha}$ in the brain tissues by using 2% 2,3,5-triphenyltetrazolium chloride (TTC) staining and immunohistochemistry. YST treatment showed a significant decrease of infarct size and volume induced by MCAO in diabetic rats. YST treatment showed a significant decrease of c-Fos and Bax positive neurons in cortex penumbra. YST treatment showed a decrease of HIF-l${\alpha}$ positive neurons in cortex penumbra, but it was not significant statistically. These results suggest that YST has effects on neuroprotection against cerebral infarct under diabetic condition. And it is supposed that neuroprotective effect of YST reveals by anti-apoptosis mechanism.
This study aimed to investigate the cerebroprotective effect of vascular endothelial growth factor (VEGF) on permanent focal cerebral ischemia in Sprague-Dawley rats. Right middle cerebral artery (MCA) was occluded for 6 and 24 hours by an intraluminal monofilament technique. An open cranial window was made on the right parietal bone for determination of continuous changes in regional cerebral blood flow (rCBF) by laser-Doppler flowmetry. The infarct size was morphometrically determined using the 2,3,5-triphenyltetrazolium chloride technique. Brain edema was determined by measuring brain water content. In normal rats, rCBF was significantly increased by intravenous infusion of VEGF for 10 minutes. The VEGF-induced increase in rCBF was significantly inhibited by pretreatment with suramin, a heparin-binding growth factor inhibitor as well as $N^{\omega}-nitro-L-arginine$, a nitric oxide synthase inhibitor. In focal cerebral ischemic rats, the amplitude of decrease in rCBF during ischemic period was significantly less in VEGF-treated group, compared with that in vehicle-treated group. The cerebral infarct size was reduced by VEGF in a dose-dependent manner. The brain edema formation was dose-dependently reduced by VEGF in 24-hour MCA occlusion group but not in 6-hour MCA occlusion group. It is suggested that VEGF not only improves the rCBF during cerebral ischemic period but also reduces the brain edema formation, and thereby exert a protective effect on focal cerebral ischemia in rats.
The present study examined influence of various ischemic duration on extent of focal ischemic brain injury induced by middle cerebral artery occlusion (MCAO) in rats. The MCAO was produced by insertion of a 17 mm silicone-coated 4-0 nylon surgical thread to the origin of MCA through the internal carotid artery for 30, 60, 90, 120 min (transient) or 24 hr (permanent) in male Sprague-Dawley rats under isoflurane anesthesia. Reperfusion in transient MCAO models was achieved by pulling the thread out of the internal carotid artery. Only rats showing neurological deficits characterized by left hemiparesis and/or circling to the left, were included in cerebral ischemic groups. The rats were sacrificed 24 hr after MCAO and seven serial coronal slices of the brain were stained with 2,3,5-triphenyltetrazolium chloride. Infarct size was measured using a computerized image analyzer. Ischemic damage was common in the frontoparietal cortex (somatosensory area) and the lateral segment of the striatum while damage to the medial segment of the striatum depended on the duration of the occlusion. In the 30-min MCAO grouts, however, infarcted region was primarily confined to the striatum and it was difficult to clearly delineate the region since there was mixed population of live and dead cells in the nucleus. Infarct volume was generally increased depending on the duration of MCAO, showing the most severe damage in the permanent MCAO group. However, there was no significant difference in infarct size between the 90-min and 120-min MCAO groups. % Edema also tended to increase depending on the duration of MCAO. The results suggest that the various focal ischemic rat models established in the present study can be used to evaluate in vivo neuroprotective activities of candidate compounds or to elucidate pathophysiological mechanisms of ischemic neuronal cell death.
Kwak, Dong Hoon;Kim, Sung Min;Lee, Dea Hoon;Kim, Ji Su;Kim, Sun Mi;Lee, Seo Ul;Jung, Kyu Yong;Seo, Byoung Boo;Choo, Young Kug
Molecules and Cells
/
v.20
no.3
/
pp.354-360
/
2005
Neuronal damage subsequent to transient cerebral ischemia is a multifactorial process involving several overlapping mechanisms. Gangliosides, sialic acid-conjugated glycosphingolipids, reduce the severity of acute brain damage in vitro. However their in vivo effects on the cerebral cortex damaged by ischemic infarct are unknown. To assess the possible protective role of gangliosides we examined their expression in the cerebral cortex damaged by ischemic infarct in the rat. Ischemia was induced by middle cerebral artery (MCA) occlusion, and the resulting damage was observed by staining with 2, 3, 5-triphenylterazolium chloride (TTC). High-performance thin-layer chromatography (HPTLC) showed that gangliosides GM3 and GM1 increased in the damaged cerebral cortex, and immunofluorescence microscopy also revealed a significant change in expression of GM1. In addition, in situ hybridization demonstrated an increase in the mRNA for ganglioside GM3 synthase. These results suggest that gangliosides GM1 and GM3 may be synthesized in vivo to protect the cerebral cortex from ischemic damage.
Journal of Physiology & Pathology in Korean Medicine
/
v.19
no.4
/
pp.993-999
/
2005
This research was peformed to investigate protective effect of Sophora Subprostrata fractions against focal ischemic brain damage after middle cerebral artery(MCA) occlusion using intraluminal suture. Rats were divided into six groups: MCA-occluded group(Control): each administered groups with Sophora Subprostrata total phase(Total), Sophora Subprostrata Aqueous phase (Aqueous), Sophora Subprostrata BuOH phase(BuOH), and Sophora Subprostrata Alkaloid phase(Alkaloid) after MCA-occlusion; sham-operated group(Sham). The right MCA was occluded by A poly-L-lysine coated 4-0 nylon suture thread through the internal carotid artery permanently. Sophora Subprostrata and fractions were administered orally(Smg/ml) for 7 days after MCA-occlusion. The Drain tissue was stained with $2\%$ triphenyl tetrazolium chloride on ischemic brain tissue(2mm section). The results showed that 1) Sophora Subprostrata total phase reduced infarct size and total infarct volume compared to the control group at 24 hours after MCA-occlusion, 2) Sophora Subprostrata Aqueous phase reduced infarct size and total infarct volume compared to the control group at 24 hours after MCA-occlusion, 3) Sophora Subprostrata Alkaloid phase reduced infarct size compared to the control group at 24 hours after MCA-occlusion, but 4) at 7 days after MCA-occlusion, Sophora Subprostrata did not show effective recovery compared with control group. Sophora Subprostrata has protective effects against brain damage at the early stage of focal cerebral ischemia. Sophora Subprostrata total and Aqueous phase produced more pronounced protective effect against focal ischemic brain damage.
K.J. Jung;Lee, M.J.;E.Y. Cho;Y.S. Song;Lee, Y.H.;Park, Y.L.;Lee, Y.S.;C. Jin
Proceedings of the Korean Society of Applied Pharmacology
/
2003.11a
/
pp.62-62
/
2003
It is now convincing that free radical generation is involved in the pathophy siological mechanisms of ischemic stroke, particularly in ischemia-reperfusion injury. The present study, therefore, examined neuroprotective effect of aloesin isolated from Aloe vera, which was known to have antioxidative activity, in a rat model of transient focal cerebral ischemia. Transient focal cerebral ischemia was induced by occlusion of middle cerebral artery for 2 hr with a silicone-coated 4-0 nylon monofilament in male Sprague-Dawley rats under isoflurane anesthesia Aloesin (1, 3, 10, 30 and 50 mg/kg/injection) was administered intravenously 3 times at 0.5, 2 and 4 hr after onset of ischemia. Neurological score was measured 24 hr after onset of ischemia immediately before sacrifice. Seven serial coronal slices of the brain were stained with 2,3,5-triphenyltetrazolium chloride and infarct size was measured using a computerized image analyzer. Treatment with the close of 1 or 50 mg/kg did not significantly reduce infarct volume compared with the saline vehicle-treated control group. However, treatments with the closes of 3 and 10 mg/kg significantly reduced both infarct volume and edema by approximately 47% compared with the control group, producing remarkable behavioral recovery effect. Treatment with the close of 30 mg/kg also significantly reduced infarct volume to a lesser extent by approximately 33% compared with the control group, but produced similar degree of behavioral recovery effect. In addition, general pharmacological studies showed that aloesin was a quite safe compound. The results suggest that aloesin can serve as a lead chemical for the development of neuroprotective agents by providing neuroprotection against focal ischemic neuronal injury.
Acute ischemic stroke(AIS) should be diagnosed within a few hours of onset of cerebral infarction symptoms using diagnostic radiology. In this study, we evaluated the clinical usefulness of SVD and the Bayesian algorithm to measure the volume of cerebral infarction using computed tomography perfusion(CTP) imaging and magnetic resonance diffusion-weighted imaging(MR DWI). We retrospectively included 50 patients (male : female = 33 : 17) who visited the emergency department with symptoms of AIS from September 2017 to September 2020. The cerebral infarct volume measured by SVD and the Bayesian algorithm was analyzed using the Wilcoxon signed rank test and expressed as a median value and an interquartile range of 25 - 75 %. The core volume measured by SVD and the Bayesian algorithm using was CTP imaging was 18.07 (7.76 - 33.98) cc and 47.3 (23.76 - 79.11) cc, respectively, while the penumbra volume was 140.24 (117.8 - 176.89) cc and 105.05 (72.52 - 141.98) cc, respectively. The mismatch ratio was 7.56 % (4.36 - 15.26 %) and 2.08 % (1.68 - 2.77 %) for SVD and the Bayesian algorithm, respectively, and all the measured values had statistically significant differences (p < 0.05). Spearman's correlation analysis showed that the correlation coefficient of the cerebral infarct volume measured by the Bayesian algorithm using CTP imaging and MR DWI was higher than that of the cerebral infarct volume measured by SVD using CTP imaging and MR DWI (r = 0.915 vs. r = 0.763 ; p < 0.01). Furthermore, the results of the Bland Altman plot analysis demonstrated that the slope of the scatter plot of the cerebral infarct volume measured by the Bayesian algorithm using CTP imaging and MR DWI was more steady than that of the cerebral infarct volume measured by SVD using CTP imaging and MR DWI (y = -0.065 vs. y = -0.749), indicating that the Bayesian algorithm was more reliable than SVD. In conclusion, the Bayesian algorithm is more accurate than SVD in measuring cerebral infarct volume. Therefore, it can be useful in clinical utility.
Sim, Hyung Tae;Kim, Sung Ryong;Beom, Min Sun;Chang, Ji Wook;Kim, Na Rae;Jang, Mi Hee;Ryu, Sang Wan
Journal of Chest Surgery
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v.47
no.6
/
pp.510-516
/
2014
Background: Acute cerebral infarction is a major risk factor for postoperative neurologic complications in cardiac surgery. However, the outcomes associated with acute silent cerebral infarction (ASCI) have not been not well established. Few studies have reported the postoperative outcomes of these patients in light of preoperative Diffusion-weighted magnetic resonance imaging (DWI). We studied the postoperative neurologic outcomes of patients with preoperative ASCI detected by DWI. Methods: We retrospectively studied 32 patients with preoperative ASCI detected by DWI. None of the patients had preoperative neurologic symptoms. The mean age at operation was $68.8{\pm}9.5$ years. Five patients had previous histories of stroke. Four patients had been diagnosed with infective endocarditis. Single cerebral infarct lesions were detected in 16 patients, double lesions in 13, and multiple lesions (>5) in three. The median size of the infarct lesions was 4 mm (range, 2 to 25 mm). The operations of three of the 32 patients were delayed pending follow-up DWI studies. Results: There were two in-hospital mortalities. Neurologic complications also occurred in two patients. One patient developed extensive cerebral infarction unrelated to preoperative infarct lesions. One patient showed sustained delirium over one week but recovered completely without any neurologic deficits. In two patients, postoperative DWI confirmed that no significant changes had occurred in the lesions. Conclusion: Patients with preoperative ASCI showed excellent postoperative neurologic outcomes. Preoperative ASCI was not a risk factor for postoperative neurologic deterioration.
This study demonstrates the effects of Yanggyuksanhwa-Tang, Sasang constitutional herb prescription reported its clinical effect on the stroke of the So-yang In(少陽人), on the cerebral blood flow changes induced by nitro L-arginine methyl ester (L-NAME) treatment and ischemic brain damage induced by the middle cerebral artery occlusion (MCAO) in the rats. The changes of the arterial blood pressure, cerebral blood flow, and the diameter of the pial artery were measured in rats treated with L-NAME. And the changes of the infarct size, volume, and plasma tumor necrosis factor alpha ($TNF-{\alpha}$) levels were measured in the rats that the middle cerebral artery has been occluded by the intraluminal suture thread method. Yanggyuksanhwa-Tang was administered by the i.v. injection on the L-NAME treated rats, by the i.o. administration on the MCAO rats. The results is 1. The changes of the arterial blood pressure was not different statistically between in the L-NAME treated control group and in the Yanggyuksanhwa-Tang administered group. 2. Increase in the cerebral blood flow induced by L-NAME treatment was attenuated in the Yanggyuksanhwa-Tang administered group significantly (P<0.05) as compared with the L-NAME treated control group. 3. Decrease in the diameter of the pial artery induced by L-NAME treatment was attenuated about 18% in the Yanggyuksanhwa-Tang administered group as compared with the L-NAME treated control group. 4. Ischemic damaged infarct areas were decreased significantly (P<0.05) in the interaural 12mm, 10mm, and 6mm brain sections of the Yanggyuksanhwa-Tang administered group as compared the MCA occluded control group. 5. Total ischemic infarct volume was decreased significantly (P<0.05) in the Yanggyuksanhwa-Tang administered group as compared the MCA occluded control group. 6. Plasma $TNF-{\alpha}$ levels were decreased significantly (P<0.01) in the Yanggyuksanhwa-Tang administered group as compared the MCA occluded control group.
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