공진단이 MCAO모델 흰쥐에서 gliosis 억제에 미치는 영향

성기문,허래경,송봉근 대한한방내과학회 2009 大韓韓方內科學會誌 Vol.30 No.4

Objectives : In conditions of brain infarction, irreversible axon damage occurs in the central nerve system (CNS), because gliosis becomes physical and a mechanical barrier to axonal regeneration. Reactive gliosis induced by ischemic injury such as middle cerebral artery occlusion is involved with up-regulation of GFAP and CD81. The current study was to examine the effect of the Gongjin-dan (GJD) on CD81 and GFAP expression and its pathway in the rat brain following middle cerebral artery occlusion (MCAO). Methods : In order to study ischemic injuries on the brain, infarction was induced by MCAO using insertion of a single nylon thread, through the internal carotid artery, into a middle cerebral artery. Cresyl violet staining, cerebral infarction size measurement, immunohistochemistry and microscopic examination were used to detect the expression of CD81 and GFAP and the effect on the infarct size and pyramidal cell death in the brain of the rat with cerebral infarction induced by MCAO. Also, c-Fos and ERK expression was measured to investigate the signaling pathway after GJD administration in MCAO rats. Results : The following results were obtained: Measuring the size of cerebral infarction induced by MCAO in the rat after injection of GJD showed the size was decreased. GJD administration showed pyramidal cell death protection in the hippocampus in the MCAO rat. GJD administration decreased GFAP expression in the MCAO rat. GJD administration decreased CD81 expression in the MCAO rat. GJD administration induced up-regulation of c-FOS expression compared with MCAO. GJD administration induced down-regulation of ERK expression compared with MCAO. Conclusion : We observed that GJD could suppress the reactive gliosis, which disturbs the axonal regeneration in the brain of the rat with cerebral infarction after MCAO by controlling the expression of CD81 and GFAP. The effect may be modulated by the regulation of c-Fos and ERK. These results suggest that GJD can be a candidate to regenerate CNS injury. Objectives : In conditions of brain infarction, irreversible axon damage occurs in the central nerve system (CNS), because gliosis becomes physical and a mechanical barrier to axonal regeneration. Reactive gliosis induced by ischemic injury such as middle cerebral artery occlusion is involved with up-regulation of GFAP and CD81. The current study was to examine the effect of the Gongjin-dan (GJD) on CD81 and GFAP expression and its pathway in the rat brain following middle cerebral artery occlusion (MCAO). Methods : In order to study ischemic injuries on the brain, infarction was induced by MCAO using insertion of a single nylon thread, through the internal carotid artery, into a middle cerebral artery. Cresyl violet staining, cerebral infarction size measurement, immunohistochemistry and microscopic examination were used to detect the expression of CD81 and GFAP and the effect on the infarct size and pyramidal cell death in the brain of the rat with cerebral infarction induced by MCAO. Also, c-Fos and ERK expression was measured to investigate the signaling pathway after GJD administration in MCAO rats. Results : The following results were obtained: Measuring the size of cerebral infarction induced by MCAO in the rat after injection of GJD showed the size was decreased. GJD administration showed pyramidal cell death protection in the hippocampus in the MCAO rat. GJD administration decreased GFAP expression in the MCAO rat. GJD administration decreased CD81 expression in the MCAO rat. GJD administration induced up-regulation of c-FOS expression compared with MCAO. GJD administration induced down-regulation of ERK expression compared with MCAO. Conclusion : We observed that GJD could suppress the reactive gliosis, which disturbs the axonal regeneration in the brain of the rat with cerebral infarction after MCAO by controlling the expression of CD81 and GFAP. The effect may be modulated by the regulation of c-Fos and ERK. These results suggest that GJD can be a candidate to regenerate CNS injury.

공진단이 MCAO모델 흰쥐에서 gliosis 억제에 마치는 영향

성기문,허래경,송봉곤,Seong, Kee-Moon,Hae, Rae-Kyong,Song, Bong-Keun 대한한방내과학회 2009 大韓韓方內科學會誌 Vol.30 No.4

Objectives : In conditions of brain infarction, irreversible axon damage occurs in the central nerve system (CNS), because gliosis becomes a physical and a mechanical barrier to axonal regeneration. Reactive gliosis induced by ischemic injury such as middle cerebral artery occlusion is involved with up-regulation of GFAP and CD81. This study was undertaken to examine the effect of the Gongjin-dan (GJD) on CD81 and GFAP expression and its pathway in the rat brain following middle cerebral artery occlusion (MCAO). Methods : In order to study ischemic injuries on the brain, infarction was induced by MCAO using insertion of a single nylon thread, through the internal carotid artery, into a middle cerebral artery. Cresyl violet staining, cerebral infarction size measurement, immunohistochemistry and microscopic examination were used to detect the expression of CD81 and GFAP and the effect on the infarct size and pyramidal cell death in the brain of the rat with cerebral infarction induced by MCAO. Also, c-Fos and ERK expression were measured to investigate the signaling pathway after GJD administration in MCAO rats. Results : Measuring the size of cerebral infarction induced by MCAO in the rat after injection of GJD showed the size had decreased. GJD administration showed pyramidal cell death protection in the hippocampus in the MCAO rat. GJD administration decreased GF AP expression in the MCAO rat. GJD administration decreased CD81 expression in the MCAO rat. GJD administration induced up-regulation of c-FOS expression compared with MCAO. GJD administration induced down-regulation of ERK expression compared with MCAO. Conclusion : We observed that GJD could suppress the reactive gliosis, which disturbs the axonal regeneration in the brain of a rat with cerebral infarction after MCAO by controlling the expression of CD81 and GFAP. The effect may be modulated by the regulation of c-Fos and ERK. These results suggest that GJD can be a candidate to regenerate CNS injury.

조구등이 MCAO 모델 흰쥐에서 gliosis 억제에 미치는 영향

김상우,김선애,송봉근,Kim, Sang-Woo,Kim, Sun-Ae,Song, Bong-Keun 대한한방내과학회 2010 大韓韓方內科學會誌 Vol.31 No.4

Objectives : In condition of brain infarction, irreversible axon damage occurs in central nerve system(CNS), because gliosis becomes physical and mechanical barrier to axonal regeneration. Reactive gliosis induced by ischemic injury such as middle cerebral artery occlusion is involved with up-regulation of GFAP and CD81. The current study is to examine the effect of the Uncariae Ramulus et Uncus on CD81 and GFAP expression in the rat brain following middle cerebral artery occlusion. Methods : In order to study ischemic injuries on brain, infarction was induced by middle cerebral artery occlusion(MCAO) using insertion of a single nylon thread, through the internal carotid artery, into a middle cerebral artery. Cresyl violet staining, cerebral infarction size measurement, immunohistochemistry and microscopic examination were used to detect the expression of CD81 and GFAP and the effect on the infarct size and pyramidal cell death in the brain of the rat with cerebral infarction induced by MCAO. Results : The following results were obtained 1. Measuring the size of cerebral infartion induced by MCAO in the rat after injection of Uncariae Ramulus et Uncus showed the size was decreased. 2. Intravenous injection of Uncariae Ramulus et Uncus showed pyramidal cell death protection in the hippocampus in the MCAO rat. 3. Water extract injection of Uncariae Ramulus et Uncus decreased GFAP expression significantly in the MCAO rat. 4. Uncariae Ramulus et Uncus water extract decreased CD81 expression in the MCAO rat. 5. The administration of water extract of Uncariae Ramulus et Uncus induced up-regulation of c-Fos expression significantly compared with MCAO. 6. The admistration of water extract of Uncariae Ramulus et Uncus increased ERK expression significantly compared with MCAO. Conclusion : We observed that Uncariae Ramulus et Uncus could suppress the reactive gliosis, which disturbs the axonal regeneration in the brain of the rat with cerebral infaction after MCAO by controlling the expression of CD81 and GFAP. The effect may be modulated by the up-regulation of c-Fos and ERK. These results suggest that Uncariae Ramulus et Uncus can be a candidate to regenerate CNS injury.

성향정기산이 흰쥐의 MCAO에 의한 국소뇌허혈에 미치는 영향

김효선,김연섭,Kim, Hyo-Sun,Kim, Youn-Sub 대한동의생리학회 2006 동의생리병리학회지 Vol.20 No.6

This study evaluated neuroprotective effect of Sunghyangjungki-San (SHS) on the focal cerebral ischemia. The rats were induced infarct in cerebral cortex and caudoputamen by using temporal occlussion of the middle cerebral artery (MCAO), then water extract of SHS was treated for MCAO rats. Neuroprotective effect was evaluated by neurological score, infarct sizes and total volume, positive neurons against Bax, Caspase-3, HSP-72, and $HIF-1{\alpha}$ in infarct area with immunohistochemistry. The results obtained were as follows: Treatment of SHS improved neurological score of MCAO rats, but there was not a statistical significance. Treatment of SHS reduced significantly infarct sizes in the brain sections of MCAO rats. Treatment of SHS reduced significantly total volume of infarct of MCAO rats. Treatment of SHS reduced significantly Bax positive neurons in penumbra of cerebral cortex of MCAO rats. Treatment of SHS reduced significantly Caspase-3 positive neurons in caudoputamen and penumbra of cerebral cortex of MCAO rats. Treatment of SHS reduced significantly HSP-72 positive neurons in penumbra of cerebral cortex of MCAO rats. Treatment of SHS reduced significantly $IF-1{\alpha}$ positive neurons in penumbra of cerebral cortex of MCAO rats.

청폐사간탕(淸肺潟肝湯)이 MCAO에 의한 흰쥐의 뇌허혈 손상에 미치는 영향

정광식,김범회,황원덕,Jung, Gwang-Sik,Kim, Bum-Hoi,Hwang, Won-Duk 대한예방한의학회 2009 대한예방한의학회지 Vol.13 No.1

This study aimed to validate neuroprotective effect of Chungpaesagan-tang on the early stage of cerebral ischemic damage. Cerebral ischemic damage was induced by the middle cerebral artery occlusion (MCAO) for 2 hours in the Sprague-Dawley rats. Water extract of Chungpaesagan-tang(8.7g/kg) was administered orally twice at 1 and 4 hours after the MCAO. Neurological score was tested at 3 and 24 hours after the MCAO and Chungpaesagan-tang administration. At 24 hours after the MCAO, infarct volume and edema ratio was evaluated with the TTC staining. Apoptotic cell death in cerebral cortex and caudate putamen was observed with cresyl violet staining and TUNEL labeling. Bax expression in the MCAO rat brain was stained with immunohistochemistry. Chungpaesagan-tang improved neurological and behavioral impairment of the MCAO rats and reduced infarct area, infarct volume and brain edema formation. Chungpaesagan-tang attenuated cell death percentage in cortex penumbra and reduced TUNEL positive cells in cortex penumbra and in caudate putamen of the MCAO rats. Chungpaesagan-tang reduced Bax positive neurons in caudate putamen and reduced c-Fos positive neurons in cortex penumbra of the MCAO rats. Chungpaesagan-tang intensified neuronal HSP72 expression in cortex penumbra of the MCAO rats. In results, Chunpaesagan-tang reduces infarct volume and edema formation through anti-apoptotic effect. This result suggests that Chunapaesagan-tang has an adequate neuroprotective effect on the early stage of cerebral ischemic damage.

홍경천 투여와 수영훈련이 MCAO 유발 쥐의 infarct volume과 근기능에 미치는 영향

이정필 ( Jeong Pil Lee ),김호성 ( Ho Sung Kim ),김상훈 ( Sang Hoon Kim ),강명희 ( Myoung Hee Kang ),장석암 ( Seok Am Zhang ),오재근 ( Jae Keun Oh ) 한국운동영양학회 2005 Physical Activity and Nutrition (Phys Act Nutr) Vol.9 No.1

The aim of this study was to determine the effects of Rhodiola sachalinensis (RS) administration and regular swim exercise on infarct volume and motor functions in middle cerebral artery occlusion (MCAO) rats. Brain ischemic condition was induced by MCAO. Forty rats were divided into MCAO and Sham groups based on pre-treatments, and each group was further divided into four subgroups; the MCAO group as regular swim exercise and RS administration(MHE), RS administration (MH), regular swim exercise (ME), control (MC) and Sham group as regular swim exercise and RS administration (SHE), RS administration(SH), regular swim exercise (SE), control (SC). Then, the rats underwent either swim training (30min·d^(-1)) and/or RS administration (100 mg/kg) for 7 consecutive days. TTC (2,3,5-triphenyltetrazolium chloride) staining and western blotting were conducted to assess infarct volume and expression of vascular endothelial growth factor (VEGF) in the injured hemisphere of the MCAO group (ipsilateral hemisphere in the Sham). Foot fault test, balance beam test and prehensile traction test were conducted to access motor functions at the 3rd and 10th day after treatments. The infarct volumes were significantly decreased in ME, MHE (p<.001) and MH (p<.01) compared to MC. The VEGF (vascular endothelial growth factor) expression was significantly higher in ME compared to MHE, MH (p<.01) and MC, SE (p<.001). There was significantly negative correlation between infarct volume and VEGF expression (p<.01). Motor functions were significantly worsened in MCAO compared to shams (p<.001), but all experimental treatment were improved in Motor functions in all MCAO groups (except MC) whereas no significant changes were founded in Sham. These observations suggest that RS administration and swimming training can reduce infarct volume leading to improved motor functions in MCAO rats.

두충(杜衝)이 근육위축 흰쥐의 후지 근섬유형 및 MyoD 발현에 미치는 영향

윤덕영 ( Duk Young Yun ),박성하 ( Seong Ha Park ),이종수 ( Jong Soo Lee ) 한방재활의학과학회 2008 한방재활의학과학회지 Vol.18 No.1

Objectives : Eucommiae cortex is reported that it helps bone and skeletal muscle stronger. In case of bone, many report is presented, but reports related to skeletal muscle are rarely existed. So in order to investigate effects of Eucommiae cortex on the skeletal muscle atrophy following stroke, cerebral infarct was induced by the middle cerebral artery occlusion (MCAO) in the rats. Methods : In order to induce MCAO rats, nylon suture was advanced and then blocked middle cerebral artery(MCA). Water extract of Eucommiae cortex was treated for 15 days, once a day orally, after the MCAO. Effects were evaluated with muscle weights, muscle fiber type composition, cross-sectioned area of muscle fibers in soleus and gastrocnemius of the unaffected and affected hind limbs. And MyoD protein expression in gastrocnemius was demonstrated with immunohistochemistry and western blotting. Results : In the affected hind limb of the MCAO rats, muscle weight loss of gastrocnemius and tibialis anterior muscles were attenuated by Eucommiae cortex treatment. In soleus muscle of the affected hind limb of the MCAO rats, increase of type-I fibers and decrease of type-II fibers were induced by Eucommiae cortex treatment. In soleus muscle of the affected hind limb of the MCAO rats, decrease of cross-sectioned areas of type-I fibers was attenuated by Eucommiae cortex treatment. In gastrocnemius muscle of the affected hind limb of the MCAO rats, increase of type-I fibers and decrease of type-II fibers were induced by Eucommiae cortex treatment. In gastrocnemius muscle of the affected hind limb of the MCAO rats, decreases of cross-sectioned areas of type-I and type-II fibers were attenuated by Eucommiae cortex treatment. In gastrocnemius muscle of the affected hind limb of the MCAO rats, MyoD positive cells were increased by Eucommiae cortex treatment. In gastrocnemius muscles both of the affected and unaffected hind limb of the MCAO rats, MyoD expressions were increased by Eucommiae cortex treatment. Conclusions : These results suggest that Eucommiae cortex has a protective effect against muscle atrophy, through the inhibition of the muscle cell apoptosis, following the central nervous system demage.

The Effects of Glutamate NMDA Receptor Antagonist MK-801 on Gastrointestinal Motility after Middle Cerebral Artery Occlusion in Rats

Nasir Hussin Ameer,이재희,최명애,Guang-Shi Jin,김미선,박병림 대한약리학회 2010 The Korean Journal of Physiology & Pharmacology Vol.14 No.3

This study was performed to investigate the role of glutamate neurotransmitter system on gastrointestinal motility in a middle cerebral artery occlusion (MCAO) model of rats. The right middle cerebral artery was occluded by surgical operation, and intestinal transit and geometric center as a parameter of gastrointestinal motility and expression of c-Fos protein in the insular cortex and cingulate cortex were measured at 2 and 12 h after MCAO. Intestinal transit was 66.3±7.5% and 62.3±5.7% 2 and 12 h after sham operation, respectively, and MCAO significantly decreased intestinal transit to 39.0±3.5% and 47.0±5.1% at 2 and 12 h after the occlusion, respectively (p<0.01). The geometric center was 5.6±0.4 and 5.2±0.9 at 2 and 12 h after sham operation, respectively, and MCAO significantly decreased geometric center to 2.9±0.8 and 3.0±0.3 at 2 and 12 h after the occlusion, respectively (p<0.01). In control animals, injection of atropine decreased intestinal transit to 35.9±5.2%, and injection of glutamate NMDA receptor antagonist, MK-801, decreased intestinal transit to 28.8±9.5%. Pretreatment with MK-801, a glutamate NMDA receptor antagonist, in the MCAO group decreased intestinal transit to 11.8±3.2%, which was significantly decreased compared to MCAO group (p<0.01). MCAO markedly increased the expression of c-Fos protein in the insular cortex and cingulate cortex ipsilateral to the occlusion 2 h after MCAO, and pretreatment with MK-801 produced marked reduction of c-Fos protein expression compared to MCAO group (p<0.01). These results suggest that modulation of gastrointestinal motility after MCAO might be partially mediated through a glutamate NMDA receptor system.

The Effects of Glutamate NMDA Receptor Antagonist MK-801 on Gastrointestinal Motility after Middle Cerebral Artery Occlusion in Rats

Ameer, Nasir Hussin,Lee, Jae-Hee,Choi, Myoung-Ae,Jin, Guang-Shi,Kim, Min-Sun,Park, Byung-Rim The Korean Society of Pharmacology 2010 The Korean Journal of Physiology & Pharmacology Vol.14 No.3

This study was performed to investigate the role of glutamate neurotransmitter system on gastrointestinal motility in a middle cerebral artery occlusion (MCAO) model of rats. The right middle cerebral artery was occluded by surgical operation, and intestinal transit and geometric center as a parameter of gastrointestinal motility and expression of c-Fos protein in the insular cortex and cingulate cortex were measured at 2 and 12 h after MCAO. Intestinal transit was $66.3{\pm}7.5%$ and $62.3{\pm}5.7%$ 2 and 12 h after sham operation, respectively, and MCAO significantly decreased intestinal transit to $39.0{\pm}3.5%$ and $47.0{\pm}5.1%$ at 2 and 12 h after the occlusion, respectively (p<0.01). The geometric center was $5.6{\pm}0.4$ and $5.2{\pm}0.9$ at 2 and 12 h after sham operation, respectively, and MCAO significantly decreased geometric center to $2.9{\pm}0.8$ and $3.0{\pm}0.3$ at 2 and 12 h after the occlusion, respectively (p<0.01). In control animals, injection of atropine decreased intestinal transit to $35.9{\pm}5.2%$, and injection of glutamate NMDA receptor antagonist, MK-801, decreased intestinal transit to $28.8{\pm}9.5%$. Pretreatment with MK-801, a glutamate NMDA receptor antagonist, in the MCAO group decreased intestinal transit to $11.8{\pm}3.2%$, which was significantly decreased compared to MCAO group (p<0.01). MCAO markedly increased the expression of c-Fos protein in the insular cortex and cingulate cortex ipsilateral to the occlusion 2 h after MCAO, and pretreatment with MK-801 produced marked reduction of c-Fos protein expression compared to MCAO group (p<0.01). These results suggest that modulation of gastrointestinal motility after MCAO might be partially mediated through a glutamate NMDA receptor system.

속단(續斷)이 중풍모델 흰쥐 비목근의 근섬유위축 및 MyoD 발현에 미치는 영향

한상우,류사현,심은섭,이동은,박민희,김범회,최현,정혁상,손낙원,손영주,Han, Sang-Woo,Ryu, Sa-Hyun,Shim, Eun-Sheb,Lee, Dong-Eun,Park, Min-Hee,Kim, Bum-Hoi,Choi, Hyun,Jung, Hyuk-Sang,Sohn, Nak-Won,Sohn, Young-Joo 대한본초학회 2008 大韓本草學會誌 Vol.23 No.2

Objectives : The present study has been undertaken to investigate the effects of Dipsaci Radix on Muscle Fiber Atrophy and MyoD Expression in Gastrocnemius of MCAO Rats Methods : In order to investigate effects of Dipsaci radix on the skeletal muscle atrophy following stroke, cerebral infarct was induced by the middle cerebral artery occlusion (MCAO) in the rats. Water extract of Dipsaci radix (184.4 mg/100 g) was treated for 4 weeks, once a day orally, after the MCAO. Effects were evaluated with muscle fiber type composition and cross-sectioned area of muscle fibers in gastrocnemius of the unaffected & affected hind limbs. And MyoD protein expression in gastrocnemius was demonstrated with immunohistochemistry and western blotting. Results : Obtained results were as follows; 1. Infarct volume was not attenuated by Dipsaci radix treatment in the MCAO rats. 2. At the affected-side hind limb of the MCAO rats, the increase of type-I fibers and the decrease of type-II fibers were induced by Dipsaci radix treatment. 3. At the affected-side hind limb of the MCAO rats, decreases of cross-sectioned areas of type-I and type-II fibers were attenuated by Dipsaci radix treatment. 4. At the affected-side hind limb of the MCAO rats, MyoD positive cells were increased by Dipsaci radix treatment. 5. At the affected-side hind limb of the MCAO rats, MyoD expressions were increased by Dipsaci radix treatment. Conclusions : These results suggest that Dipsaci radix has a protective effect against muscle atrophy, through the inhibition of the muscle cell apoptosis, following the central nervous system demage.