• Journal of Oriental Neuropsychiatry
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• v.18 no.1
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• pp.153-171
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• 2007

Objective : The aim of this study was to investigate effects of Gagambosim-Tang(GBT) of focal brain ischemic injury induced by intraluminal filament insertion in the rats. Method : The ischemia was induced by intraluminal filament insertion into middle cerebral artery Eight-arm radial maze was designed for the behavioral task. Gagambosim-Tang was orally administrated in SD rats for 21 days. The task was started on the 4th week after focal brain injury, and performed two trials per day for 6days. The effects of Gagambosim-Tang on neuroprotective agents in cresyl violet, choline acetyltranferase(ChAT), nerve growth factor (NGF)-stain and c-Fos with ischemic injury were investigated. Results : The errors in the eight-arm radial maze task were significantly decreased in normal group compared with control group on 2-6days, GBT lX(42.2 mg/ml)orally administrated group on 1days, GBT 6X(253.2 mg/ml) on 3, 5, 6days. The rate of correct choice was increased in normal and GBT 6X groups. The neuroprotective effect in the hippocampal CA1 was increased in normal and GBT 1X, GBT 6X groups compared with control group. The density of ChAT in the hippocampal CA1 was increased in normal and GBT6X groups compared with control group. The density of NGF in the hippocampal CA1 was increased normal and GBT6X groups compared with control group. The number of c-Fos-positive neurons in the hippocampal CA1 was increased in normal and GBT 6X groups compared with control group. Conclusion : These results suggest that Gagambosim-Tang may have protective effect on dementia.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.2
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• pp.145-152
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• 2017

Remote ischemic preconditioning (RIPC) is an intrinsic phenomenon whereby 3~4 consecutive ischemia-reperfusion cycles to a remote tissue (non-cardiac) increases the tolerance of the myocardium to sustained ischemia-reperfusion induced injury. Remote ischemic preconditioning induces the local release of chemical mediators which activate the sensory nerve endings to convey signals to the brain. The latter consequently stimulates the efferent nerve endings innervating the myocardium to induce cardioprotection. Indeed, RIPC-induced cardioprotective effects are reliant on the presence of intact neuronal pathways, which has been confirmed using nerve resection of nerves including femoral nerve, vagus nerve, and sciatic nerve. The involvement of neurogenic signaling has been further substantiated using various pharmacological modulators including hexamethonium and trimetaphan. The present review focuses on the potential involvement of neurogenic pathways in mediating remote ischemic preconditioning-induced cardioprotection.

• Toxicological Research
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• v.11 no.1
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• pp.161-168
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• 1995

It has been found that various stress challenges induce the myocardial antioxidant enzymes and produce an acquisition of the cellular resistance to the ischemic injury in animal hearts. Most of the stresses, however, seem to be guite dangerous to an animal's life. In the present study, therefore, we tried to search for safely applicable stress modalities which could lead to the induction of antioxidant enzymes and the production of myocardial tolerance to the ischemia-reperfusion injury. Male Sprague-Dawley rats (200-250 g) were exposed to various non-fatal stress conditions, i.e., hyperthermia (environmental temperature of $42^{\circ}C$ for 30 min, non-anesthetized animal), iramobilization (60 min), treadmill exercise (20 m/min, 30min), swimming (30 min), and hyperbaric oxyflenation (3 atm, 60 min), once a day for 5 days. The activities of myocardial antioxidant enzymes and the ischemia-reperfusion injury of isolated hearts were evaluated at 24 hr after the last application of the stresses. The activities of antioxidant enzymes, superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase (G6PD), were assayed in the freshly excised ventricular tissues. The ischemia-reperfusion injury was produced by 20 min-global ischemia followed by 30 min-reperfusion using a Langendorff perfusion system. In swimming and hyperbaric oxygenation groups, the activities of SOD and G6PD increased significantly and in the hyperthermia group, the catalase activity was elevated by 63% compared to the control. The percentile recoveries of cardiac function at 30 min of the post-ischemic reperfusion were 55.4%, 73.4%, and 74.2% in swimming, the hyperbaric oxygenation and the hyperthermia groups, respectively. The values were significantly higher than that of the control (38.6%). In additions, left ventricular end-diastolic pressure and lactate dehydrogenase release were significantly reduced in the stress groups. The results suggest that the antioxidant enzymes in the heart could be induced by the apparently safe in vivo-stresses and this may be involved in the myocardial protection from the ischemia-reperfusion injury.

• The Journal of Korean Physical Therapy
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• v.15 no.4
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• pp.199-207
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• 2003

This review describes the neurophathological mechanisms that are implicated in perinatal brain injury. Perinatal brain injury is the most important cause of morbidity and mortality to infants, often leading to spastic motor deficits, mental retardation, seizures, and learning impairments. The immature brain injury is usually caused by cerebral hypoxia-ischemia, hemorrhage, or infection. The important form of perinatal brain injury is the hypoxic-ischemic injury and the cerebral hemorrhage. The pathology of hypoxic-ischemic injury include delayed energy failure by mitochondrial dysfunction, neuronal excitotoxicity and vulnerability of white matter in developing brain. The immature brain has the fragile vascular bed of germinal matrix and can not effectively centralize their circulation. Therefore, the cerebral hemorrhage process is considered to be involved in the periventricular leukomalacia.

• Journal of Ginseng Research
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• v.47 no.2
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• pp.199-209
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• 2023

Background: Due to the interrupted blood supply in cerebral ischemic stroke (CIS), ischemic and hypoxia results in neuronal depolarization, insufficient NAD+, excessive levels of ROS, mitochondrial damages, and energy metabolism disorders, which triggers the ischemic cascades. Currently, improvement of mitochondrial functions and energy metabolism is as a vital therapeutic target and clinical strategy. Hence, it is greatly crucial to look for neuroprotective natural agents with mitochondria protection actions and explore the mediated targets for treating CIS. In the previous study, notoginseng leaf triterpenes (PNGL) from Panax notoginseng stems and leaves was demonstrated to have neuroprotective effects against cerebral ischemia/reperfusion injury. However, the potential mechanisms have been not completely elaborate. Methods: The model of middle cerebral artery occlusion and reperfusion (MCAO/R) was adopted to verify the neuroprotective effects and potential pharmacology mechanisms of PNGL in vivo. Antioxidant markers were evaluated by kit detection. Mitochondrial function was evaluated by ATP content measurement, ATPase, NAD and NADH kits. And the transmission electron microscopy (TEM) and pathological staining (H&E and Nissl) were used to detect cerebral morphological changes and mitochondrial structural damages. Western blotting, ELISA and immunofluorescence assay were utilized to explore the mitochondrial protection effects and its related mechanisms in vivo. Results: In vivo, treatment with PNGL markedly reduced excessive oxidative stress, inhibited mitochondrial injury, alleviated energy metabolism dysfunction, decreased neuronal loss and apoptosis, and thus notedly raised neuronal survival under ischemia and hypoxia. Meanwhile, PNGL significantly increased the expression of nicotinamide phosphoribosyltransferase (NAMPT) in the ischemic regions, and regulated its related downstream SIRT1/2/3-MnSOD/PGC-1α pathways. Conclusion: The study finds that the mitochondrial protective effects of PNGL are associated with the NAMPT-SIRT1/2/3-MnSOD/PGC-1α signal pathways. PNGL, as a novel candidate drug, has great application prospects for preventing and treating ischemic stroke.

• Archives of Reconstructive Microsurgery
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• v.9 no.2
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• pp.103-109
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• 2000

Purpose : We performed this study in order to analyze the clinical results of functioning gracilis musculocutaneous free flap transplantation for reconstructon of hand function in cases of Volkmann's ischemic contracture and massive soft tissue injury of forearm. Materials and methods : 18 cases were reviewed with 5 yeas of mean follow up period. We evaluated total active motion of the finger joints and wrist, pinch and grip strength. Results : The flap were survived in 17 cases and 1 case was failed due to infection. The sum of active motion of finger joints(TAM) was improved from 0 to $173.8^{\circ}$. The average grip and pinch strength was improved from 0 kg to $2.7{\pm}2.1kg$ and from 0 kg to $2.4{\pm}1.6kg$. Conclusion : The results in most cases were acceptable in relatively long term follow-up. It may be an option for reconstruction of hand function in cases of Volkmann's ischemic contracture and traumatic upper extremity injury.

• Journal of Chest Surgery
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• v.21 no.6
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• pp.979-983
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• 1988

Calcium channel blockers may prevent myocardial injury during cardioplegia and reperfusion. This study was done to evaluate the effects of diltiazem cardioplegia on myocardial protection during ischemic arrest and recovery of myocardial function after reperfusion. Four formulations of crystalloid cardioplegic solutions, GIK solution[group I, n=12], diltiazem[lug/ml GIK] in GIK solution[group II, n=7], ],diltiazem[2ug/ml GIK] in GIK solution[group III, n=6] and diltiazem[4ug/ml GIK] in GIK solution[group IV, n=6] were compared in isolated working rat heart subjected to a long period [2 hours] of hypothermic arrest with multi-dose infusion. Diltiazem cardioplegia[group II, III and IV]was found to be superior in nearly all aspects. Diltiazem cardioplegia showed faster recovery of regular rhythm and lower incidence of ventricular fibrillation than group I did. In comparing mechanical function in all experimental hearts, the mean postischemic recoveries of aortic flow, cardiac output, peak aortic pressure, stroke volume and stroke work[expressed as a percentage of its preischemic control] were significantly greater in group II, III and IV[diltiazem cardioplegia] than in group I. The infused amount of cardioplegic solution was more increased by the addition of diltiazem to GI K solution. [p < 0.01] Creatine kinase leakage tended to be lower in hearts receiving diltiazem cardioplegia, especially in group III and IV[p<0.05] than in those receiving GIK solution only[group I]. Diltiazem cardioplegia results in the increased flow of cardioplegic solution and the decreased ischemic injury of myocardium during ischemic arrest and the improved recovery of myocardial function after reperfusion, and a dose-response relation must be established before clinical use.

• YAKHAK HOEJI
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• v.44 no.4
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• pp.371-377
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• 2000

In order to investigate the pharmacological properties of fractions of Astragali Radix and Polygalae Radix, the effects of the fractions on cerebral ischemia and subsequent reperfusion were studied. Brain ischemia was induced by bilateral common carotid artery occlusion in mongolian gerbil. Brains were recirculated for 30 mins after the 20 min occlusion. Methanol and butanol fractions of Astragali Radix and Polygalae Radix were administered orally 2 hrs before common carotid artery occlusion. Histological observations showed that brain ischemia induced severe brain damage evidenced by the presence of necrotic foci, edema and hemorrhage. This injury was prevented by the methanol fraction and butanol fraction of Polygalae Radix. The level of ATP in brain tissue significantly decreased in ischemic gerbils. This decrease was prevented by the pretreatment with butanol fraction of Polygalae Radix. In contrast, the levels of lactate and lipid peroxide were both elevated in ischemic gerbils. This elevation was inhibited by the pretreatments with methanol fraction and butanol fraction of Polygalae Radix. Our findings suggest that the Polygalae Radix improves ischemia-induced brain damage.

• Archives of Pharmacal Research
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• v.28 no.12
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• pp.1392-1399
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• 2005

This study evaluated the effect of $\alpha$-tocopherol ($\alpha$-TC), ischemic preconditioning (IPC) or a combination on the extent of mitochondrial injury caused by hepatic ischemia/reperfusion (I/R). Rats were pretreated with $\alpha$-TC (20 mg/kg per day, i.p.) for 3 days before sustained ischemia. A rat liver was preconditioned with 10 min of ischemia and 10 min of reperfusion, and was then subjected to 90 min of ischemia followed by 5 h or 24 h of reperfusion. I/R increased the aminotransferase activity and mitochondrial lipid peroxidation, whereas it decreased the mitochondrial glutamate dehydrogenase activity. $\alpha$-TC and IPC individually attenuated these changes. $\alpha$-TC combined with IPC ($\alpha$-TC+IPC) did not further attenuate the changes. The mitochondrial glutathione content decreased after 5 h reperfusion. This decrease was attenuated by $\alpha$-TC, IPC, and $\alpha$-TC+IPC. The significant production of peroxides observed after 10 min reperfusion subsequent to sustained ischemia was attenuated by $\alpha$-TC, IPC, and $\alpha$-TC+IPC. The mitochondria isolated after I/R were rapidly swollen. However, this swelling rate was reduced by $\alpha$­TC, IPC, and $\alpha$-TC+IPC. These results suggest that either $\alpha$-TC or IPC reduces the level of mitochondrial damage associated with oxidative stress caused by hepatic I/R, but $\alpha$- TC combined with IPC offers no significant additional protection.

• Advances in Traditional Medicine
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• v.9 no.4
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• pp.292-302
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• 2009

Ischemia/reperfusion injury, which is commonly seen in the field of renal surgery or transplantation, is a major cause of acute renal failure. Previous studies showed that antioxidant treatments attenuated renal ischemia/reperfusion injury. The objective of this study was to examine the role of hesperidin in modulating reactive oxygen species induced inflammation and apoptosis after renal ischemia/reperfusion injury. Rats were subjected to right nephrectomy, 15 days later 45 min of renal ischemia and 24 h reperfusion with or without treatment with hesperidin. Renal function, inflammation and apoptosis were compared at 24 h after reperfusion injury. Hesperidin improved the renal dysfunction and reduced inflammation and apoptosis after ischemia/reperfusion injury. In conclusion, hesperidin shows potent anti-apoptotic and antiinflammatory properties due to antioxidant property. These findings may have major implications in the treatment of human ischemic acute renal failure.