• Animal cells and systems
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• v.16 no.4
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• pp.302-312
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• 2012

The purpose of this study was to examine whether Phellodendri Cortex extract (PCE) could improve learning and memory impairments caused by lipopolysaccharide (LPS)-induced inflammation in the rat brain. The effect of PCE on modulating pro-inflammatory mediators in the hippocampus and its underlying mechanism were investigated. Injection of LPS into the lateral ventricle caused acute regional inflammation and subsequent deficits in spatial learning ability in the rats. Daily administration of PCE (50, 100, and 200 mg/kg, i.p.) for 21 days markedly improved the LPS-induced learning and memory disabilities in the Morris water maze and passive avoidance test. PCE administration significantly decreased the expression of pro-inflammatory mediators such as tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$, and cyclooxygenase-2 mRNA in the hippocampus, as assessed by RT-PCR analysis and immunohistochemistry. Together, these findings suggest that PCE significantly attenuated LPS-induced spatial cognitive impairment through inhibiting the expression of pro-inflammatory mediators in the rat brain. These results suggested that PCE may be effective in preventing or slowing the development of neurological disorders, including Alzheimer's disease, by improving cognitive and memory function because of its anti-inflammation activity in the brain.

• Molecules and Cells
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• v.40 no.3
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• pp.186-194
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• 2017

A brain-enriched secreting signal peptide, NELL2, has been suggested to play multiple roles in the development, survival, and activity of neurons in mammal. We investigated here a possible involvement of central NELL2 in regulating feeding behavior and metabolism. In situ hybridization and an immunohistochemical approach were used to determine expression of NELL2 as well as its colocalization with proopiomelanocortin (POMC) and neuropeptide Y (NPY) in the rat hypothalamus. To investigate the effect of NELL2 on feeding behavior, 2 nmole of antisense NELL2 oligodeoxynucleotide was administered into the lateral ventricle of adult male rat brains for 6 consecutive days, and changes in daily body weight, food, and water intake were monitored. Metabolic state-dependent NELL2 expression in the hypothalamus was tested in vivo using a fasting model. NELL2 was noticeably expressed in the hypothalamic nuclei controlling feeding behavior. Furthermore, all arcuatic POMC and NPY positive neurons produced NELL2. The NELL2 gene expression in the hypothalamus was up-regulated by fasting. However, NELL2 did not affect POMC and NPY gene expression in the hypothalamus. A blockade of NELL2 production in the hypothalamus led to a reduction in daily food intake, followed by a loss in body weight without a change in daily water intake in normal diet condition. NELL2 did not affect short-term hunger dependent appetite behavior. Our data suggests that hypothalamic NELL2 is associated with appetite behavior, and thus central NELL2 could be a new therapeutic target for obesity.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.3
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• pp.287-295
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• 1998

Diazepam is known to have cardiovascular depressive effects through a combined action on benzodiazepinergic receptor and the GABA receptor-chloride ion channel complex. Moreover, it is known that barbiturates also have some cardiovascular regulatory effects mediated by the central GABAergic system. Therefore, this study was undertaken to delineate the regulatory actions and interactions of these systems by measuring the responses of the cardiovascular system and renal nerve activity to muscimol, diazepam and pentobarbital, administered intracerebroventricularly in rabbits. When muscimol $(0.03{\sim}0.3\;{\mu}\;g/kg)$, diazepam $(10{\sim}100\;{\mu}\;g/kg)$ and pentobarbital $(1{\sim}10\;{\mu}\;g/kg)$ were injected into the lateral ventricle of the rabbit brain, there were similar dose-dependent decreases in blood pressure (BP) and renal nerve activity (RNA). The relative potency of the three drugs in decreasing BP and RNA was muscimol ＞ pentobarbital ＞ diazepam. Muscimol and pentobarbital also decreased the heart rate in a dose-dependent manner; however, diazepam produced a trivial, dose-independent decrease in heart rate. Diazepam $(30\;{\mu}g/kg)$ augmented the effect of muscimol $(0.1\;{\mu}g/kg)$ in decreasing blood pressure and renal nerve activity, but pentobarbital $(3\;{\mu}g/kg)$ did not. Bicuculline $(0.5\;{\mu}g/kg)$, a GABAergic receptor blocker, significantly attenuated the effect of muscimol in decreasing BP and RNA, either alone or with diazepam, and that of pentobarbital in decreasing BP and RNA, either alone or with muscimol. We inferred that the central benzodiazepinergic and barbiturate systems help regulate peripheral cardiovascular function by modulating the GABAergic system, which adjusts the output of the vasomotor center and hence controls peripheral sympathetic tone. Benzodiazepines more readily modulate the GABAergic system than barbiturates.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.3
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• pp.307-312
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• 1998

This study was performed to investigate the mechanism of central analgesic effects of antidepressants. Thirty four male rats were anesthetized with pentobarbital sodium (40 mg/kg, ip). A stainless steel guide cannula and a PE tube (PE10) were implanted into the lateral ventricle and cisterna magna area. Stimulating and recording electrodes were implanted into the incisor pulp and anterior digastric muscle. Electrodes were led subcutaneously to the miniature cranial connector sealed on the top of the skull with acrylic resin. The jaw opening reflex was used in freely moving rats, and antidepressants were administered intracisternally in order to eliminate the effects of anesthetic agents on the pain assessment and evaluate the importance of the central action site of antidepressants. After 48 hours of recovery from surgery, digastric electromyogram (dEMG) of freely moving rats was recorded. Electrical shocks (200 ${\mu}sec$ duration, 0.5-2 mA intensity) were delivered at 0.5 Hz to the dental pulp every 2 minute. Intracisternal administration of $15\;{\mu}g$ imipramine suppressed dEMG elicited by noxious electrical stimulation in the tooth pulp to $76{\pm}6%$ control. Intracisternal administration of $30\;{\mu}g$ desipramine, nortriptyline, or imipramine suppressed dEMG remarkably to $48{\pm}2,\;27{\pm}8,\;or\;25{\pm}5%$ of the control, respectively. Naloxone, methysergide, and phentolamine blocked the suppression of dEMG produced by intracisternal antidepressants from $23{\pm}2\;to\;69{\pm}4%,\;from\;32{\pm}5\;to\;80{\pm}9%,\;and\;from\;24{\pm}6\;to\;77{\pm}5%$ of the control, respectively. These results indicate that antidepressants produce antinociception through central mechanisms in the orofacial area. Antinociception of intracisternal antidepressants seems to be mediated by an augmentation of descending pain inhibitory influences on nociceptive pathways.

• Journal of Chest Surgery
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• v.30 no.6
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• pp.613-616
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• 1997

We present a case of 58-year-old (tamale with dilated cardiomyopathy(DCMP) in whom we performed left ventricular(LV) remodeling surgery(Batista operation) to reduce the left ventricle diameter and improve left ventricular unction. The patient was admitted September 1996 with heart failure NYHA class IV. There was severe orthopnea and peripheral edema. 2-D echocardiography(Echo) showed DCMP with the ejection fraction(EF) I5%, LV end diastolic dimension(LVEDD) 80mm, mitral regurgitation(MR) grade IV, tricuspid regurgitation ('m) grade ll. Preoperative cardiac output(CO) was 1.5/L/min and cardiac index(Cl) was 1.0 L/min/m2. We proceeded with LV remodeling surgery by resection a part of LV lateral wall between both papillary muscle, from the mitral annulus to the LV apex. Size of resected LV wall was 90 $\times$ 100 $\times$ 15 mm. At the mean time, mitral valve and tricuspid valve were repaired. Postoperative 2-D Echo showed the EF 37%, LVEDD 50 mna, trivial MR, no TR. CO was 3.SL/min and Cl was 2.3 L/min/m2. Her fuctional NYHA class was 1.

• Herbal Formula Science
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• v.27 no.2
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• pp.137-149
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• 2019

Objective : This study is conducted in order to investigate the effect of Banggibongnyeongtang(BBT) on Lipopolysaccharide (LPS)-induced depression. Method : LPS $5{\mu}g$ was injected to lateral ventricle. Experimental groups were administered BBT intraperitoneally. Depressive behavior was confirmed by weight change, sucrose preference, open field test(OFT), and forced swimming test(FST). The plasma concentration of $IL-1{\beta}$ and $TNF-{\alpha}$, Corticotropin-Releasing Factor(CRF), Adrenocorticotropin Hormone(ACTH) and Corticosterone(CORT) were measured by ELISA. Result : BBT did not change the body weight significantly than LPS group, but on sucrose preference, BBT increased significantly in LPS+BBT400 group compared to LPS group (P<0.05). In the OFT, BBT increased spending time in the central zone and decreased grooming number. LPS+BBT400 group increased central zone-spending time, and decreased grooming number than LPS group significantly (P<0.05). In the FST, LPS+BBT400 group decreased immobility time than LPS group significantly (P<0.05). BBT decreased $IL-1{\beta}$ concentration does-dependently, but only with significant decrease in LPS+BBT400 group than LPS group in plasma (P<0.05). But BBT did not decrease $TNF-{\alpha}$ concentration significantly in plasma. BBT decreased plasma CRF, ACTH, and CORT. And CRH and CORT of LPS+BBT400 group were shown significant decrease comparing with LPS group (P<0.05). Conclusion : It is postulated that the anti-depressant effect of BBT can be validated through inhibition of HPA axis abnormal activity by the anti-inflammatory effect.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.212-212
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• 1996

Effects of ginseng total saponin(GTS) on changes in the glutamatergic nervous system induced by AF64A were studied in rats. Rats were pretreated with the infusion of AF64A (3mM) into lateral ventricle and were posttreated with GTS (50mg/kg, j.p) for 1 week. Twenty four hrs after the last administration, rats were sacrified and each brain resions was dissected ; striatum, hippocampus and frontal cortex. At each brain regions, total glutamate and other amino acids levels, [$^3$H]MK801 binding sites and glutamine synthetase activity were measured using HPLC-ECD, ligand binding assay and enzyme activity assay, respectively. The AF64-induced increase in the levels of total glutamate in hippocampus were significantly decreased by the administration of GTS. Furthermore, that compared with saline and GTS was decreased in striatum. The levels of total GABA compared with saline and GTS were declined in frontal cortex. Moreover, the AF64A-induced decrease in the levels of total taurine were significantly increased by the administration of GTS to extents of normal states. The numbers of [$^3$H]MK801 binding sites were differently affected in brain resiojns ; the decrease in hippocampus and no change in both striatum and frontal cortex, Glutamine synthetase activity was significantly increased in hippocampus. In comparision with saline and GTS, that was significantly decreased in striatum These results suggest that GTS may adjust the levels of glutamate, GABA and taurine constantly and may induce increase of glutamine synthetase activity declined.

• Journal of Korean Neurosurgical Society
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• v.66 no.4
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• pp.400-408
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• 2023

Objective : Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a crucial factor for the survival of neuron. The role of NMNAT2 in damage following traumatic brain injury (TBI) remains unknown. This study was designed to investigate the role of NMNAT2 in TBI-induced neuronal degeneration and neurological deficits in rats. Methods : The TBI model was established in Sprague-Dawley rats by a weight-dropping method. Real-time polymerase chain reaction, western blot, immunofluorescence, Fluoro-Jade C staining, and neurological score analyses were carried out. Results : NMNAT2 mRNA and protein levels were increased in the injured-side cortex at 6 hours and peaked 12 hours after TBI. Knocking down NMNAT2 with an injection of small interfering RNA in lateral ventricle significantly exacerbated neuronal degeneration and neurological deficits after TBI, which were accompanied by increased expression of BCL-2-associated X protein (Bax). Conclusion : NMNAT2 expression is increased and NMNAT2 exhibits neuroprotective activity in the early stages after TBI, and Bax signaling pathway may be involved in the process. Thus, NMNAT2 is likely to be an important target to prevent secondary damage following TBI.

• Journal of Chest Surgery
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• v.36 no.7
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• pp.457-462
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• 2003

Background: Surgical results of the Fontan procedures in patients with a single ventricle have improved. As the perioperative mortality continues to decline and late outcome is forthcoming, attention is now being directed toward late complications of the Fontan procedures. We retrospectively analyzed our experience with reoperations after Fontan procedures. Material and Method: Between January 1988 and December 2002, 24 patients underwent reoperations after Fontan procedures. The median age at Fontan procedures and reoperation was 3.3 years and 9.2 years, respectively. Types of initial Fontan procedures were atriopulmonary connection (n＝11), lateral tunnel Fontan (n＝11), and extracardiac conduit Fontan (n＝2). Indications for reoperation included atrioventricular valve regurgitation (n＝7), atrial arrhythmia (n＝8), Fontan pathway stenosis (n＝7), residual right-to-left shunt (n＝5), etc. Result: Procedures performed at reoperation included atrioventricular valve replacement (n＝6), conversion to lateral tunnel Fontan (n＝5), conversion to extracardiac conduit Fontan (n＝3), cryoablation of arrhythmia circuit (n＝7), etc. There was no operative mortality. There were 2 late deaths. Mean follow-up duration was 2.7$\pm$2.1 years. All patients except two were in NYHA class I at the latest follow-up. Among 8 patients with preoperative atrial arrhythmia, postoperative conversion to normal sinus rhythm was achieved in 7 patients. Conclusion: Reoperations after Fontan procedures could be achieved with low mortality and morbidity. Reoperation may lead to clinical improvement in patients with specific target conditions such as atrioventricular valve regurgitation, refractory atrial arrhythmia, or Fontan pathway stenosis, especially in patients with previous atriopulmonary connection.

• Applied Microscopy
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• v.29 no.1
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• pp.11-23
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• 1999

Ultrastructure of the ependymal cells of X-irradiated rats on their head were studied. Rats weighing $200\sim250gm$ were X-irradiated on their head and neck areas. Total exposures were 3,000 rads or 6,000 rads depending on experimental groups. And irradiated rats were sacrificed on 6 hours, 2 days and 6 days following the radiation exposures. Animals were perfused through the heart with 1% glutaraldehyde-1% paraformaldehyde solution, under ether-anesthesia. The tissues from the wall of lateral ventricles were fixed in the 2% osmium tetroxide solution. The results observed with electron microscope were as follow: 1. In 6 hours group, many ependymal cells were swelled, luminal portions of cytoplasms of some cells protruded into the ventricular lumen, and many cilia were lost or irregularly altered. 2. In 2 days group, ependymal cells were swelled more severely and subependymal edema were pronounced. 3. Protruded cytoplasm contained usually basal bodies of cilia, groups of mitochondria, endoplasmic reticula , etc. 4. Following X-irradiations, some protruded masses contained neural elements including the axon terminals with dense core vesicles. Axons and axon terminals were also found in the enlarged intercellular spaces among ependymal cells. From the above results, the heavy irradiation on the head area of the rat induced alteration of the ependymal cells lining the lateral ventricle. Hence the ependymal functions of selective barrier, protective barrier, and metabolic barrier could be altered following X-irradiation on the head.