• The Korean Journal of Food And Nutrition
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• v.29 no.6
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• pp.923-929
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• 2016

The purpose of this study was to evaluate the protective effect of $PineXol^{(R)}$ on $H_2O_2$-induced cell death in SK-N-MC cells, and in early stage focal ischemia rodent model. SK-N-MC cells were pre-treated with $200{\mu}M$ $H_2O_2$ or various concentrations of $PineXol^{(R)}$ (10, 30, and 50 pg/mL) for 24 h, and then exposed to $H_2O_2$ for 3 h. Cell death was assessed by the CCK-8 assay, reactive oxygen species (ROS) assay, and lactate and dehydrogenase (LDH) release assay. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) expressions were also analyzed by western blotting. Focal ischemia rodent model was used as the in vivo model, and different concentrations of $PineXol^{(R)}$ (1, 10, and 100 mg/kg) were administered. One week after administration, reduction of infarct volume was analyzed by TTC staining. Cell viability of $H_2O_2$-treated SK-N-MC cells significantly increased by pre-treatment of $PineXol^{(R)}$ (p<0.05). $PineXol^{(R)}$ pre-treatment also induced significant decrease of ROS and LDH expressions. However, $PineXol^{(R)}$ did not affect the infarct volume. These results suggest that $PineXol^{(R)}$ has significant neuroprotective effect in vitro, but statistical significance was not confirmed in the in vivo focal ischemia model.

• Journal of Korean Neurosurgical Society
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• v.30 no.1
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• pp.12-19
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• 2001

Objective : Albumin is a very useful drug for the improving of cerebral blood volume and the oncotic effect in cerebral ischemia or cerebral vasospasm. The purpose of this study was to examine the morphological and neurological effect of albumin therapy on reperfusion injury following transient focal cerebral ischemia. Materials and Methods : 18 Male Sprague-Dawley rats weighing 270-320g were used. The ischemia model was produced by 2-hour period of transient middle cerebral artery occlusion with a poly-L-lysin coated intraluminal suture. The agent(20% human serum albumin[HSA]) or control solution(NaCl 0.9%) was administered intravenously at a dosage of 1% of body weight immediate after reperfusion following a 2-hour period occlusion. Neurological function was evaluated by the postural reflex and the forlimb placing test during occlusion(at 60 min) and daily for 3 days thereafter. The brain was perfusion-fixed, and infarct volumes and brain edema were measured. Results : The HSA significantly improved the neurological score in treated group. The rats of albumin treatment group showed significantly reduced total infarct volume(by 34%) and brain edema(by 81%) compared with salinetreated rats. Conclusion : HSA showed a substantial effect on the transient focal cerebral ischemia and reperfusion injury model. These results may indicate its usefulness in treating reperfusion injury patients after thrombolysis treatment for the thrombo-embolic major cerebral artery occlusions.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.62-62
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• 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.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.303.1-303.1
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• 2002

Recent studies have suggested that the cerebral ischemia induced the neuronal cell death by mediating multiple mechanisms with necrosis and/or apoptosis. The present study examined neuroprotective mechanism of aloesin against transient focal cerebral ischemia. Aloesin. main component of aloe possesses various biological activates such as wound healing. anti-gastric ulcer. and chemopreventive activity. Transient focal cerebral ischemia was induced by 120 min MCAO. (omitted)

• Biomedical Science Letters
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• v.11 no.2
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• pp.201-209
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• 2005

This study aimed to investigate the cerebroprotective effect of nociceptin on transient focal cerebral ischemia in Sprague-Dawley rats by determining the changes in regional cerebral blood flow (rCBF) and the infarct size. Right middle cerebral artery (MCA) was occluded for 2 hours, and thereafter was followed by reperfusion by an intraluminal monofilament technique. An open cranial window was made on the right parietal bone for determination of continuous changes in rCBF by laser-Doppler flowmetry. The infarct size was morphometrically determined using the 2,3,5-triphenyltetrazolium chloride technique. In normal rats, nociceptin ($0.01\~100\;nmol/kg$, Lv.) increased rCBF and decreased cerebral arterial resistance in a dose-dependent manner. Systemic arterial blood pressure was little affected by nociceptin at the doses of 0.01 and 0.1nmol/kg, but dose-dependently reduced at the doses of 1 nmol/kg or more. In transient cerebral ischemic rats, nociceptin ($0.01\~0.1$ nmol/kg, i.p.) significantly attenuated the postischemic cerebral hyperemia, and progressively increased rCBF. The improving effect of nociceptin on the postischemic rCBF response was markedly blocked by pretreatment with $[Nphe^1]nociceptin(1-13)NH_2$ (1 nmol/kg, i.p.), a selective nociceptin receptor antagonist, but not by naloxone ($3{\mu}mol/kg$, i.p.), a selective opioid receptor antagonist. The cerebral infarct size was significantly reduced by nociceptin ($0.01\~0.1$ nmol/kg) administered i.p. 5 min after MCA occlusion in transient cerebral ischemia of 2-hour MCA occlusion and 22-hour reperfusiion. It is suggested that nociceptin improves the postischemic cerebral hemodynamics and thereby has a cerebroprotective effect in transient focal cerebral ischemia.

• Nutrition Research and Practice
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• v.4 no.3
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• pp.196-202
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• 2010

To investigate the neuroprotective effects of bovine colostrums (BC), we evaluate the ability of consuming BC after focal brain ischemia/reperfusion injury rat model to reduce serum cytokine levels and infarct volume, and improve neurological outcome. Sprague-Dawley rats were randomly divided into 4 groups; one sham operation and three experimental groups. In the experimental groups, MCA occlusion (2 h) and subsequent reperfusion (O/R) were induced with regional cerebral blood flow monitoring. One hour after MCAO/R and once daily during the experiment, the experimental group received BC while the other groups received 0.9% saline or low fat milk (LFM) orally. Seven days later, serum pro-inflammatory cytokine (IL-$1{\beta}$, IL-6, and TNF-${\alpha}$) and anti-inflammatory cytokine (IL-10) levels were assessed. Also, the infarct volume was assessed by using a computerized image analysis system. Behavioral function was also assessed using a modified neurologic severity score and corner turn test during the experiment. Rats receiving BC after focal brain I/R showed a significant reduction (-26%/-22%) in infarct volume compared to LFM/saline rats, respectively (P < 0.05). Serum IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ levels were decreased significantly in rats receiving BC compared to LFM/saline rats (P < 0.05). In behavioral tests, daily BC intake showed consistent and significant improvement of neurological deficits for 7 days after MCAO/R. BC ingestion after focal brain ischemia/reperfusion injury may prevent brain injury by reducing serum pro-inflammatory cytokine levels and brain infarct volume in a rat model.

• Biomedical Science Letters
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• v.11 no.3
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• pp.355-363
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• 2005

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.

• Journal of Korean Neurosurgical Society
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• v.41 no.1
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• pp.30-38
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• 2007

Objective : To elucidate the role of aquaporin-4[AQP4] in cerebral edema formation, we studied the expression and subcellular localization of AQP4 in astrocytes after focal cerebral ischemia. Methods : Cerebral ischemia were induced by permanent middle cerebral artery[MCA] occlusion in rats and estimated by the discoloration after triphenyltetrazolium chloride[TTC] immersion. Change of AQP4 expression were evaluated using western blot. Localization of AQP4 was assessed by confocal microscopy and its interaction with ${\alpha}-syntrophin$ was analyzed by immunoprecipitation. Results : After right MCA occlusion, the size of infarct and number of apoptotic cells increased with time. The ratio of GluR1/GluR2 expression also increased during ischemia. The polarized localization of AQP4 in the endfeet of astrocytes contacting with ventricles, vessels and pia mater was changed into the diffuse distribution in cytoplasm. The interactions of AQP4 and Kir with ${\alpha}-syntrophin$, an adaptor of dystrophin complex, were disrupted by cerebral ischemia. Conclusion : The deranged spatial buffering function of astrocytes due to mislocalized AQP4/Kir4.1 channel as well as increased assembly of $Ca^{2+}$ permeable AMPA receptors might contribute to the development of edema formation and the excitotoxic neuronal cell death during ischemia.

• The Journal of Korean Medicine
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• v.21 no.1
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• pp.11-19
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• 2000

The present study was carried out to investigate the effects of Woowhangcheongshim-won(WCW) on the extracellular concentrations of amino acid neurotransmitters(glutamate, aspartate, GABA, glycine, taurine, alanine, and tyrosine) and organic acid (lactate and pyruvate) in striatum and cerebral infarction volume in rats subjected to permanent focal cerebral ischemia induced by 2 hours of middle cerebral artery occlusion(MCAO), using intracerebral microdialysis as the sampling technique, Microdialysis probes were inserted into the lateral part of the caudate-putamen 2 hours before the experiment and microdialyzates were collected at 20min intervals and analyzed by high performance liquid chromatography, WCW significantly decreased the infarction volume with reducing focal cerebral ischemia-induced increase of extracellular glutamate, asparate, and tyrosine. On the other hand, the increase of GABA and taurine was enhanced after treatment of WCW in the ischemia-induced rats, These results suggest that WCW can produce a neuroprotective effect against cerebral ischemia by regulating extracellular excitatory and inhibitory amino acid levels in relation to the concept of excitotoxicity in brain ischemia.

• Biomolecules & Therapeutics
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• v.25 no.4
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• pp.383-389
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• 2017

Dexmedetomidine is an ${\alpha}2$-adrenergic receptor agonist that exhibits a protective effect on ischemia-reperfusion injury of the heart, kidney, and other organs. In the present study, we examined the neuroprotective action and potential mechanisms of dexmedetomidine against ischemia-reperfusion induced cerebral injury. Transient focal cerebral ischemia-reperfusion injury was induced in Sprague-Dawley rats by middle cerebral artery occlusion. After the ischemic insult, animals then received intravenous dexmedetomidine of $1{\mu}g/kg$ load dose, followed by $0.05{\mu}g/kg/min$ infusion for 2 h. After 24 h of reperfusion, neurological function, brain edema, and the morphology of the hippocampal CA1 region were evaluated. The levels and mRNA expressions of interleukin-$1{\beta}$, interleukin-6 and tumor nevrosis factor-${\alpha}$ as well as the protein expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-${\kappa}Bp65$, inhibitor of ${\kappa}B{\alpha}$ and phosphorylated of ${\kappa}B{\alpha}$ in hippocampus were assessed. We found that dexmedetomidine reduced focal cerebral ischemia-reperfusion injury in rats by inhibiting the expression and release of inflammatory cytokines and mediators. Inhibition of the nuclear factor-${\kappa}B$ pathway may be a mechanism underlying the neuroprotective action of dexmedetomidine against focal cerebral I/R injury.