• Journal of Korean Medicine Rehabilitation
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• v.18 no.2
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• pp.45-60
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• 2008

Objectives : Sopung-tang(Shufeng-tang) is a famous herbal prescription that treated ischemic brain injury. This study was designed to evaluate the effects of Sopung-tang(Shufeng-tang) on congnition and motor function recovery after ischemic brain injury in rats. Methods : Male rats were divided into 4 groups. Those rats caused ischemic brain injury by occlusion of MCA as Longa method. Control group I was per os normal saline for 7 days after ischemic brain injury. Control group II was per os normal saline for 14 days after ischemic brain injury. Experimental group I(Ex I) was taken with Sopung-tang(Shufeng-tang) for 7 days after ischemic brain injury. Experimental group II(Ex II) was taken with Sopung-tang(Shufeng-tang) for 14 days after ischemic brain injury. The author carried out neurological, cognitive motor behavior tests and histological assessment. Neurological motor behavior tests consist of limb placement test, beam-walking test and horizontal wire test. Morris water maze test was used for cognitive motor behavior test. In the histological assessment test, TTC(2,3,5-triphenylteterazolium chloride) staining, Hematoxylin & Eosin staining and immunohistochemical staining were experimented. Results : 1. In neurological motor behavior tests, motor function recovery was significantly increased in the experimental groups as compared with control groups(p<0.05). Especially Ex II was significantly increased as compared with Ex I(p<0.05). 2. In Morris water maze test, congnitive motor function recovery was significantly increased in the experimental groups as compared with control group(p<0.05). Especially Ex II was significantly increased as compared with Ex I(p<0.05). 3. In the immunohistochemical staining for the expression of BDNF in hippocampus, more immune reaction was investigated in the experimental groups as compared with control groups. Especially most immune reaction was experimented in the EX II. Conclusions : According to the above results, Sopung-tang(Shufeng-tang) can treat on the congnition and motor function recovery after ischemic brain injury in rats. And it is effective method in expression of BDNF in hippocampus.

• Biomolecules & Therapeutics
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• v.32 no.3
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• pp.319-328
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• 2024

Lysophosphatidic acid receptor 1 (LPA₁) plays a critical role in brain injury following a transient brain ischemic stroke. However, its role in permanent brain ischemic stroke remains unknown. To address this, we investigated whether LPA₁ could contribute to brain injury of mice challenged by permanent middle cerebral artery occlusion (pMCAO). A selective LPA₁ antagonist (AM152) was used as a pharmacological tool for this investigation. When AM152 was given to pMCAO-challenged mice one hour after occlusion, pMCAO-induced brain damage such as brain infarction, functional neurological deficits, apoptosis, and blood-brain barrier disruption was significantly attenuated. Histological analyses demonstrated that AM152 administration attenuated microglial activation and proliferation in injured brain after pMCAO challenge. AM152 administration also attenuated abnormal neuroinflammatory responses by decreasing expression levels of pro-inflammatory cytokines while increasing expression levels of anti-inflammatory cytokines in the injured brain. As underlying effector pathways, NF-κB, MAPKs (ERK1/2, p38, and JNKs), and PI3K/Akt were found to be involved in LPA₁-dependent pathogenesis. Collectively, these results demonstrate that LPA₁ can contribute to brain injury by permanent ischemic stroke, along with relevant pathogenic events in an injured brain.

• Physical Therapy Korea
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• v.16 no.4
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• pp.44-52
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• 2009

It is known that individual factors as cognitive, perception, emotion, and motivation may greatly influence on recovery from neurologic region. This study was to investigate the effects of environmental reinforcement through motivation to perform the tasks voluntarily on motor and cognition function in rats with focal ischemic brain injury. Focal ischemic brain injury was induced in Sprague-Dawley rats (15 rats, $250{\pm}50$ g) through middle cerebral artery occlusion (MCAo). And then, experiment groups were randomly divided into three groups; The control group: MCAo induction ($n_1$=5), the environmental reinforcement (ER) group: the application for ER after MCAo induction ($n_2$=5), the environmental reinforcement through motivation (ERM) group: the application for ERM after MCAo induction ($n_3$=5). The climbing test (CT) and the modified limb placing tests (MLPTs) to measure the motor function and the Morris water maze acquisition test (MWMAT) and the Morris water maze retention test (MWMRT) to measure the cognitive function were performed. For the CT, the ERM group was significantly larger than the ER group. For the MLPTs, the ERM group was significantly decreased compared to other groups. For the MWMAT, the time to find the circular platform in the ERM group significantly decreased compared to other groups. For the MWMRT, the time to dwell on the quadrant circular platform in the ERM group was significantly increased compared to other groups. These results suggested that the ERM could improve the motor and cognitive functions in the rats with focal ischemic brain injury.

• The Journal of Pediatrics of Korean Medicine
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• v.25 no.1
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• pp.40-48
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• 2011

Objectives: The purpose of this study is to evaluate the effect of Gonjadaesungchimjoongbang on spatial learning abilities and memories in ischemic brain injury. Methods: Rats were separated into three groups; (1) Normal, (2) Saline medication after ischemic brain injuries (control), (3) Gonjadaesungchimjoongbang medication after ischemic brain injuries (experiment). Ischemic brain injuries was induced by MCA occlusion and reperfusion. Morris water maze test was conducted for spatial learning and memory tests. Then, the change of BDNF in the hippocampus($7^{th}$, $14^{th}$ day) was examined by immunohistoche- mistry. Results: In Morris water maze test, spatial learning abilities and memory functioning were considerably increased in the experiment group as oppose to control group on $7^{th}$ and $14^{th}$ day(p<0.01). Moreover, immunohistochemistric response of BDNF in the hippocampus indicated that the more increased immune reaction was found in the experiment group as oppose to the control group on $7^{th}$ and $14^{th}$ day. Conclusions: Gonjadaesungchimjoongbang can improve the learning abilities and memories in ischemic brain injury.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.2
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• pp.91-96
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• 2007

The measurement of pathologically low levels of tissue $pO_2$ is an important diagnostic goal for determining the prognosis of many clinically important diseases including cardiovascular insufficiency, stroke and cancer. The target tissues nowaday have mostly been tumors or the myocardium, with less attention centered on the brain. Radiolabelled nitroimidazole or derivatives may be useful in identifying the hypoxic cells in cerebrovascular disease or traumatic brain injury, and hypoxic-ischemic encephalopathy. In acute stroke, the target of therapy is the severely hypoxic but salvageable tissue. $^{18}F-MISO$ PET and $^{99}mTc-EC-metronidazole$ SPECT in patients with acute ischemic stroke identified hypoxic tissues and ischemic penumbra, and predicted its outcome. A study using $^{123}I-IAZA$ in patient with closed head injury detected the hypoxic tissues after head injury. Up till now these radiopharmaceuticals have drawbacks due to its relatively low concentration with hypoxic tissues associated with/without low blood-brain barrier permeability and the necessity to wait a long time to achieve acceptable target to background ratios for imaging in acute ischemic stroke. It is needed to develop new hypoxic marker exhibiting more rapid localization in the hypoxic region in the brain. And then, the hypoxic brain imaging with imidazoles or non-imidazoles may be very useful in detecting the hypoxic tissues, determining therapeutic strategies and developing therapeutic drugs in several neurological disease, especially, in acute ischemic stroke.

• Journal of Korean Medicine Rehabilitation
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• v.18 no.3
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• pp.1-17
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• 2008

Objectives : Ohyaksungi-san(Wuyaoshunqi-san) has been used for many years as a treatment for cerebrovascular diseases in Oriental medicine. This study was designed to evaluate the effects of Ohyaksungi-san(Wuyaoshunqi-san) on cognition and motor function recovery after ischemic brain injury, and also the expression of BDNF in hippocampus. Methods : This study was designed with 4 subgroups to evaluate the effects of Ohyaksungi-san(Wuyaoshunqi-san). As control groups, group I has no treatment during 1 week after ischemic brain injury and group II has no treatment during 2 weeks after ischemic brain injury. As experimental groups, group III has been treated with Ohyaksungi-san(Wuyaoshunqi-san) during 1 week after ischemic brain injury and group IV have treated with Ohyaksungi-san(Wuyaoshunqi-san) during 2 week after ischemic brain injury. Each group has been examined by tests as follows, neurological motor behavioral tests, cognitive motor behavior test and histological test. Neurological motor behavior tests consisted of limb placement test, beam-walking test and horizontal wire test. Cognitive motor behavior test was performed by using Morris water maze. In the histological test, TTC(2,3,5-triphenylteterazolium chloride) staining, hematoxylin & eosin staining, and immunohistochemical staining were used. Results : 1. The tests for motor function recovery change had significantly good result in the experimental groups as compared with control groups(p<.05). 2. The Morris water maze test on cognition also had significantly good result in the experimental groups as compared with control groups(p<.05). 3. In the immunohistochemical staining for the expression of BDNF in hippocampus, more immune reaction was investigated in the experimental groups as compared with control groups. Especially group IV has the greatest immune reaction. Conclusions : Ohyaksungi-san(Wuyaoshunqi-san) has good effects on cognition and motor function recovery after ischemic brain injury, and also the expression of BDNF in hippocampus.

• Clinical and Experimental Pediatrics
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• v.61 no.8
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• pp.245-252
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• 2018

Purpose: This study investigated patterns of ischemic injury observed in brain images from patients with neonatal group B Streptococcal (GBS) meningitis. Methods: Clinical findings and brain images from eight term or near-term newborn infants with GBS meningitis were reviewed. Results: GBS meningitis was confirmed in all 8 infants via cerebrospinal fluid (CSF) analysis, and patients tested positive for GBS in both blood and CSF cultures. Six infants (75.0%) showed early onset manifestation of the disease (<7 days); the remaining 2 (25.0%) showed late onset manifestation. In 6 infants (75%), cranial ultrasonography showed focal or diffuse echogenicity, suggesting hypoxic-ischemic injury in the basal ganglia, cerebral hemispheres, and periventricular or subcortical white matter; these findings are compatible with meningitis. Findings from magnetic resonance imaging (MRI) were compatible with bacterial meningitis, showing prominent leptomeningeal enhancement, a widening echogenic interhemisphere, and ventricular wall thickening in all infants. Restrictive ischemic lesions observed through diffusion-weighted imaging were evident in all eight infants. Patterns of ischemic injury as detected through MRI were subdivided into 3 groups: 3 infants (37.5%) predominantly showed multiple punctuate lesions in the basal ganglia, 2 infants (25.0%) showed focal or diffuse cerebral infarcts, and 3 infants (37.5%) predominantly showed focal subcortical or periventricular white matter lesions. Four infants (50%) showed significant developmental delay or cerebral palsy. Conclusion: Certain patterns of ischemic injury are commonly recognized in brain images from patients with neonatal GBS meningitis, and this ischemic complication may modify disease processes and contribute to poor neurologic outcomes.

• Clinical and Experimental Pediatrics
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• v.64 no.8
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• pp.422-429
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• 2021

Background: Carnosine has antioxidative and neuroprotective properties against hypoxic-ischemic (HI) brain injury. Hypothermia is used as a therapeutic tool for HI encephalopathy in newborn infants with perinatal asphyxia. However, the combined effects of these therapies are unknown. Purpose: Here we investigated the effects of combined carnosine and hypothermia therapy on HI brain injury in neonatal rats. Methods: Postnatal day 7 (P7) rats were subjected to HI brain injury and randomly assigned to 4 groups: vehicle; carnosine alone; vehicle and hypothermia; and carnosine and hypothermia. Carnosine (250 mg/kg) was intraperitoneally administered at 3 points: immediately following HI injury, 24 hours later, and 48 hours later. Hypothermia was performed by placing the rats in a chamber maintained at 27℃ for 3 hours to induce whole-body cooling. Sham-treated rats were also included as a normal control. The rats were euthanized for experiments at P10, P14, and P35. Histological and morphological analyses, in situ zymography, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays, and immunofluorescence studies were conducted to investigate the neuroprotective effects of the various interventional treatments. Results: Vehicle-treated P10 rats with HI injury showed an increased infarct volume compared to sham-treated rats during the triphenyltetrazolium chloride staining study. Hematoxylin and eosin staining revealed that vehicle-treated P35 rats with HI injury had decreased brain volume in the affected hemisphere. Compared to the vehicle group, carnosine and hypothermia alone did not result in any protective effects against HI brain injury. However, a combination of carnosine and hypothermia effectively reduced the extent of brain damage. The results of in situ zymography, TUNEL assays, and immunofluorescence studies showed that neuroprotective effects were achieved with combination therapy only. Conclusion: Carnosine and hypothermia may have synergistic neuroprotective effects against brain damage following HI injury.

• Proceedings of the PSK Conference
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• 2003.10a
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• pp.106-107
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• 2003

tIn brain ischemic insult, inflammatory cells such as macrophages and lymphocytes are chemo-attracted into the brain lesion and release cytokines, resulting in an activation of microglia that are functionally equivalent to peripheral macrophages in the central nervous system. In cerebral ischemic insults, activated inflammatory cells such as microglia and macrophages may be implicated in the pattern and degree of ischemic injury by producing various bioactive mediators. (omitted)

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.3
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• pp.556-561
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• 2008

ChongMyeong-Tang (CMT) have been used clinically to treat patient with amnesia and dementia. In addition, CMT have been also used for examinee to improve learning ability in Korea. This study was designed to investigate the effects of Gagam-ChongMeong-Tang (GCMT) on cognitive dysfunction recovery after ischemic brain injury in rats. Rats were divided into three groups; (1) normal, (2) commercial diet after ischemic brain injury (control), (3) CMT diet after ischemic brain injury (experiment). In our study, we carried out Morris water maze test for cognitive motor behavior test and immunohistochemistry study through the change BDNF in the hippocampus($7^{th},\;14^{th}\;day$). In Morris water maze test, cognitive motor function recovery was significantly increased in the experiment group as compared with control group on $7^{th}\;and\;14^{th}\;day$ day (p<0.01). In immunohistochemistric response of BDNF in the hippocampus, more immune reaction was investigated in the experiment group as compared with control group on $7^{th}\;and\;14^{th}\;day$. Especially more immune reaction was experimented $14^{th}$ day. These results imply that GCMT can play a role in facilitating recovery of cognitive function after ischemic brain injury in rats.