• Biomolecules & Therapeutics
• /
• 제15권3호
• /
• pp.169-174
• /
• 2007

In the present study, we investigated the neuroprotective effects of standardized Ginkgo biloba extract (GBB) (total terpene trilactones, 13 ${\pm}$ 3%; biflavone, 4.5 ${\pm}$ 1.5%; flavonol glycoside, < 8%; proanthocyanidine, under detection limit) on ischemia-reperfusion-induced brain injury in the rats. Ischemia was induced by the intraluminal occlusion of the right middle cerebral artery for 2 h and reperfusion was continued for 22 h. GBB was orally administered, promptly prior to reperfusion and 2 h after. Total infarction volume in the ipsilateral hemispheres of ischemia-reperfusion rats were significantly reduced by treatment with GBB in a dose-dependent manner (P<0.05). The therapeutic time window of GBB was 3 h in this ischemia-reperfusion rat model. Furthermore, GBB also significantly inhibited increased neutrophil infiltration of ischemic brain tissue, as estimated by myeloperoxidase activity. These findings suggest that GBB plays a crucial protective role in ischemia-induced brain injury, in part, via inhibition of neutrophil infiltration, and suggest that this GBB could serve as a neuroprotective agent following transient focal ischemic brain injury.

• 대한한의학회지
• /
• 제21권2호
• /
• pp.68-78
• /
• 2000

Objective : This research was performed to investigate protective effects of Sophora subprostrata, against ischemic brain damage after a middle cerebral artery(MCA) occlusion. The effect was estimated using histological test, neurobehavioural test, and biochemical test. Methods : Rats(Sprague-Dawley) were divided into four groups: Sham operated group, MCA occluded group, Sophora subprostrata administrated group after MCA occlusion, and Normal group. The MCA was occluded by intraluminal method. Sophora subprostrata was administrated orally twice(l and 4 hours) after middle cerebral artery occlusion. The neurobeavioural test was performed at 3 hours, 6 hours, 9 hours and 24 hours after the surgery by posture reflex test and swimming behavioural test. All groups were sacrificed at 24 hours after the surgery. The brain tissue was stained with 2% triphenyl tetrazolium chioride(TTC) or 1 % cresyl violet solution, to examine effect of Sophora subprostrata on ischemic brain tissue. The blood samples were obtained from the heart of rats. Tumor necrosis factor-a level was measured from sera using Enzyme-Linked Immunoabsorbent Assay(ELISA). Results : The results showed that (1) Sophora subprostrata reduced infarct size and total infarct volume by 54.8% compared to the control group, (2) that neuronal death, which was shown by decrease in cell number and size, was attenuated significantly in the boundary area of the infarction, (3) that serum $TNF-{\alpha}$ㆍlevel was reduced significantly, and finally, there was significant recovery of motor deficit at 3 hours after MCA occluded by Swimming behavioural test. Conclusions :In conclusion, Sophora subprostrata has protective effects against ischemic brain damage at the early stage of ischemia.

• Laboraroty Animal Research
• /
• 제34권4호
• /
• pp.195-202
• /
• 2018

Hyperglycemia is one of the major risk factors for stroke. Hyperglycemia can lead to a more extensive infarct volume, aggravate neuronal damage after cerebral ischemia. ${\alpha}$-Synuclein is especially abundant in neuronal tissue, where it underlies the etiopathology of several neurodegenerative diseases. This study investigated whether hyperglycemic conditions regulate the expression of ${\alpha}$-synuclein in middle cerebral artery occlusion (MCAO)-induced cerebral ischemic injury. Male Sprague-Dawley rats were treated with streptozotocin (40 mg/kg) via intraperitoneal injection to induce hyperglycemic conditions. MCAO were performed four weeks after streptozotocin injection to induce focal cerebral ischemia, and cerebral cortex tissues were obtained 24 hours after MCAO. We confirmed that MCAO induced neurological functional deficits and cerebral infarction, and these changes were more extensive in diabetic animals compared to non-diabetic animals. Moreover, we identified a decrease in ${\alpha}$-synuclein after MCAO injury. Diabetic animals showed a more serious decrease in ${\alpha}$-synuclein than non-diabetic animals. Western blot and reverse-transcription PCR analyses confirmed more extensive decreases in ${\alpha}$-synuclein expression in MCAO-injured animals with diabetic condition than these of non-diabetic animals. It is accepted that ${\alpha}$-synuclein modulates neuronal cell death and exerts a neuroprotective effect. Thus, the results of this study suggest that hyperglycemic conditions cause more serious brain damage in ischemic brain injuries by decreasing ${\alpha}$-synuclein expression.

• Journal of Chest Surgery
• /
• 제57권4호
• /
• pp.342-350
• /
• 2024

Background: The maintenance of antiplatelet therapy increases the risk of bleeding during lung cancer surgery. Conversely, the perioperative interruption of antiplatelet therapy may result in serious thrombotic complications. This study aimed to investigate the safety of continuing antiplatelet therapy in the context of lung cancer surgery. Methods: We retrospectively reviewed a cohort of 498 elderly patients who underwent surgery for lung cancer. These patients were categorized into 2 groups: group N, which did not receive antiplatelet therapy, and group A, which did. Group A was subsequently subdivided into group Am, where antiplatelet therapy was maintained, and group Ai, where antiplatelet therapy was interrupted. We compared the incidence of bleeding-related and thrombotic complications across the 3 groups. Results: There were 387 patients in group N and 101 patients in group A (Ai: 70, Am: 31). No significant differences were found in intraoperative blood loss, thoracotomy conversion rates, transfusion requirements, volume of chest tube drainage, or reoperation rates for bleeding control between groups N and A or between groups Am and Ai. The duration of hospital stay was longer for group A compared to group N (7 days vs. 6 days, p=0.005), but there was no significant difference between groups Ai and Am. The incidence of cardiovascular or cerebrovascular complications did not differ significantly between groups Ai and Am. However, group Ai included a severe case of in-hospital ST-elevation myocardial infarction. Conclusion: The maintenance of antiplatelet therapy was found to be safe in terms of perioperative bleeding and thrombotic complications in elderly lung cancer surgery patients.

• 대한핵의학회지
• /
• 제28권1호
• /
• pp.37-43
• /
• 1994

심근경색후 측부순환의 존재는 심근경색의 크기를 감소시키고 생존가능한 심근의 양을 늘려 심근기능의 보존에 기여하며 심실류 혈성을 예방하는 것으로 알려져 있다. 본 연구에서는 심근경색후 측부순환의 분포와 측부순환에 따른 심근 SPECT소견을 알아보고자 시행하였다. 급성심근경색으로 진단된 환자중 2주내에 관동맥 조영술을 시행하여 TIMI grade 0, 1인 환자 56예를 대상으로 하여 측부순환이 좋은 I군과 측부순환이 나쁜 II군으로 분류하여 양군간의 임상양상 및 좌심실기능과 심근 SPECT 소견을 조사하여 다음의 결과를 얻었다. 1) 경색관련 동맥에로의 측부순환은 우관동맥 15예, 좌전하행동맥 10예, 좌회선동맥 50예 순이 었다. 2) 측부순환 경로는 좌전하행동맥에서 우관동맥으로 13예(40.6%), 우관동맥에서 좌전하행동맥으로 9예(28.1%)로 우관동맥과 좌전하행동맥 사이에 흔하였다. 3) 최고 CK 활성도는 I군에서 낮은 경향이 있었다. 4) $^{99m}Tc$-MIBI 심근 SPECT상 측부순환로가 발달한 I군에서 경색부위 가역성 관류결손 부위 빈도가 높았다 (83.4% vs 15.3%, p<0.05). 5) LVEDV, LVESV, EF는 두 군간에 차이가 없었다. 관동맥 조영술상 측부순환로의 존재는 $^{99m}Tc$-MIBI 심근 SPECT의 가역성 관류결손 부위와 유의한 연관성이 있었으며, 심근 SPECT는 기능적 측부순환을 관찰하는데 유용한 검사로 생각된다.

• The Korean Journal of Physiology and Pharmacology
• /
• 제21권5호
• /
• pp.475-485
• /
• 2017

The present study aimed to explore the neuroprotective effect and possible mechanisms of rhGLP-1 (7-36) against transient ischemia/reperfusion injuries induced by middle cerebral artery occlusion (MCAO) in type 2 diabetic rats. First, diabetic rats were established by a combination of a high-fat diet and low-dose streptozotocin (STZ) (30 mg/kg, intraperitoneally). Second, they were subjected to MCAO for 2 h, then treated with rhGLP-1 (7-36) (10, 20, $40{\mu}g/kg$ i.p.) at the same time of reperfusion. In the following 3 days, they were injected with rhGLP-1 (7-36) at the same dose and route for three times each day. After 72 h, hypoglycemic effects were assessed by blood glucose changes, and neuroprotective effects were evaluated by neurological deficits, infarct volume and histomorphology. Mechanisms were investigated by detecting the distribution and expression of the nuclear factor erythroid-derived factor 2 related factor 2 (Nrf2) in ischemic brain tissue, the levels of phospho-PI3 kinase (PI3K)/PI3K ratio and heme-oxygenase-1 (HO-l), as well as the activities of superoxide dismutase (SOD) and the contents of malondialdehyde (MDA). Our results showed that rhGLP-1 (7-36) significantly reduced blood glucose and infarction volume, alleviated neurological deficits, enhanced the density of surviving neurons and vascular proliferation. The nuclear positive cells ratio and expression of Nrf2, the levels of P-PI3K/PI3K ratio and HO-l increased, the activities of SOD increased and the contents of MDA decreased. The current results indicated the protective effect of rhGLP-1 (7-36) in diabetic rats following MCAO/R that may be concerned with reducing blood glucose, up-regulating expression of Nrf2/HO-1 and increasing the activities of SOD.

• Journal of Chest Surgery
• /
• 제38권5호
• /
• pp.323-334
• /
• 2005

배경: 유전자 치료에 의한 치료적 혈관조성은 허혈성 심질환의 새로운 치료전략의 하나로 최근 많은 연구가 진행되고 있다. 본 연구의 목적은 대동물에서 pCK 플라스미드 벡터에 혈관내피성장인자(vascular endothelial growth factor isoform 165: VEGF165) 유전자를 삽입한 pCK-VEGF를 이용한 치료적 혈관조성의 효용성을 증명하는 것이다. 대상 및 방법: 총 21 마리의 돼지를 이용하여 좌전하행지동맥의 원위부를 결찰하여 심근경색 모델을 만든 후, 4주 후에 VEGF 유전자를 삽입한 플라스미드를 심근내에 주입하거나(VEGF군), 유전자 없이 플라스미드 만을 주입하였다(대조군). 실험 대상 동물군을 맹검하에 무작위로 VEGF군 및 대조군으로 나누어 실험을 진행하였는데, 7마리는 실험 도중 사망하였으며 결과적으로 VEGF군은 8마리, 대조군은 6마리가 최종분석에 이용되었다. 좌전하행지동맥 결찰 후 30일째에 심근 SPECT와 심장초음파검사를 시행하고 심근내에 플라스미드를 주입하였으며, 이로부터 30일째에 심근 SPECT와 심장초음파검사를 다시 시행하였다. 허혈부위의 심근관류의 변화는 심근 SPECT상의 $^{99m}Tc-MIBI$의 섭취 정도로 비교하였으며, 국소 및 전체 심근기능 및 심실리모델링 등은 심장초음파 또는 게이트SPECT 검사상의 수축시 심실벽비후화, 좌심실구출률(EF), 수축기말용적(ESV), 이완기말용적(EDV) 등으로 비교하였다. 혈관조성의 정도는 조직검사상의 미세혈관의 밀도를 측정하여 비교하였다. 결과: 미세혈관의 밀도는 VEGF군에서 유의하게 더 높았으며($386\pm110/mm^{2}\;vs.\;291\pm127/mm^{2},\;p<0.001$), 분절의 관류 정도도 VEGF군에서는 관상동맥 결찰 60일째가 30일째에 비해 더 증가한 반면(플라스미드 주입 전, 후, $48.4\pm15.2\%\;vs.\;53.8\pm19.6\%,\;p<0.001$) 대조군에서는 유의한 변화가 없었고(플라스미드 주입 전, 후, $45.1\pm17.0\%\;vs.\;43.4\pm17.7\%,\;p=0.186$), 그 변화량도 두 군간에 유의한 차이를 보였다($11.4\pm27.0\%$ 증가 vs $2.7\pm19.0\%$ 감소, p=0.003). 수축시의 심실벽비후화는 양 군 모두에서 플라스미드 주입 후 유의하게 증가하였으나 증가한 정도는 두 군간에 차이가 없었다. 심장초음파검사상 ESV은 양 군 모두에서 수술 전에 비해 관상동맥 결찰 후 유의하게 증가하였고 (VEGF군, $22.9\pm9.9\;mL\;vs.\;32.3\pm9.1\;mL,\;p=0.006;$ 대조군, $26.3\pm12.0\;mL\;vs.\;36.8\pm9.7\;mL,\;p=0.046$), EF은 유의하게 감소하였으며(VEGF군, $52.0\pm7.9\%\;vs\;46.5\pm7.4\%$, p=0.004; 대조군, $48.2\pm9.2\%\;vs\;41.6\pm10.0\%$, p=0.028), EDV은 양 군 모두에서 유의한 변화가 없었다. 플라스미드 주입 전과 후의 비교에서는 양 군 모두에서 심장초음파 및 게이트 SPECT검사상의 EF, ESV, EDV 값의 유의한 차이가 없었다. 결론: VEGF165 유전자를 삽입한 플라스미드의 심근내 주입 후 허혈성 생존 심근 부위에 혈관조성이 일어나고 심근관류가 유의하게 증가하였다. 그러나 심근 기능이나 좌심실의 리모델링 경과엔 유의한 차이가 없었다.

• 대한간호학회지
• /
• 제41권2호
• /
• pp.197-203
• /
• 2011

Purpose: This study was done to identify whether pre-conditioning exercise has neuroprotective effects against cerebral ischemia, through enhance brain microvascular integrity. Methods: Adult male Sprague-Dawley rats were randomly divided into four groups: 1) Normal (n=10); 2) Exercise (n=10); 3) Middle cerebral artery occlusion (MCAo), n=10); 4) Exercise+MCAo (n= 10). Both exercise groups ran on a treadmill at a speed of 15 m/min, 30 min/day for 4 weeks, then, MCAo was performed for 90 min. Brain infarction was measured by Nissl staining. Examination of the remaining neuronal cell after MCAo, and microvascular protein expression on the motor cortex, showed the expression of Neuronal Nuclei (NeuN), Vascular endothelial growth factor (VEGF) & laminin. Results: After 48 hr of MCAo, the infarct volume was significantly reduced in the Ex+MCAo group ($15.6{\pm}2.7%$) compared to the MCAo group ($44.9{\pm}3.8%$) (p<.05), and many neuronal cells were detected in the Ex+ MCAo group ($70.8{\pm}3.9%$) compared to the MCAo group ($43.4{\pm}5.1%$) (p<.05). The immunoreactivity of laminin, as a marker of microvessels and Vascular endothelial growth factor (VEGF) were intensively increased in the Ex+MCAo group compared to the MCAo group. Conclusion: These findings suggest that the neuroprotective effects of exercise pre-conditioning reduce ischemic brain injury through strengthening the microvascular integrity after cerebral ischemia.

• Journal of Korean Neurosurgical Society
• /
• 제67권3호
• /
• pp.333-344
• /
• 2024

Objective : Markers of neuroinflammation during ischemic stroke are well characterized, but additional markers of neural damage are lacking. The study identified associations of behavioral disorders after stroke with histologic neural damage and molecular biological change. Methods : Eight-week-old, 25 g male mice of the C57BL/6J strain were subjected to middle cerebral artery occlusion (MCAO) to induce ischemic stroke. The control group was a healthy wild type (WT), and the experimental group were designed as a low severity MCAO1 and a high severity MCAO2 based on post-stroke neurological scoring. All groups underwent behavioral tests, realtime polymerase chain reaction, triphenyltetrazolium chloride (TTC) staining and Hematoxylin and Eosin staining. One-way analysis of variance was used to analyze statistical significance between groups. Results : In TTC staining, MCAO1 showed 29.02% and MCAO2 showed 38.94% infarct volume (p<0.0001). The pro-inflammatory cytokine interleukin (IL)-1β was most highly expressed in MCAO2 (WT 0.44 vs. MCAO1 2.69 vs. MCAO2 5.02, p<0.0001). From the distance to target in the Barnes maze test, WT had a distance of 178 cm, MCAO1 had a distance of 276 cm, and MCAO2 had a distance of 1051 (p=0.0015). The latency to target was 13.3 seconds for WT, 27.9 seconds for MCAO1, and 87.9 seconds for MCAO2 (p=0.0007). Prospero homeobox 1 (Prox1) was most highly expressed in MCAO2 (p=0.0004). Doublecortin (Dcx) was most highly expressed in MCAO2 (p<0.0001). Conclusion : The study demonstrated that histological damage to neural cells and changes in brain mRNA expression were associated with behavioral impairment after ischemic stroke. Prox1 and Dcx may be biomarkers of neural damage associated with long-term cognitive decline, and increased expression at the mRNA level was consistent with neural damage and long-term cognitive dysfunction.

• Journal of Yeungnam Medical Science
• /
• 제16권2호
• /
• pp.237-243
• /
• 1999

연구목적: 연구목적: $^{99m}Tc$ d,l-hexamethylpropyleneamine oxime(HMPAO)와 $^{99m}Tc$ ethyl cysteinate dimer(ECD)의 뇌세포에 의한 섭취는 뇌혈류량에 비례를 한다. 그러나 뇌혈류량이 아주 높은 경우에는 뇌세포에 의한 섭취가 그 만큼 증가를 하지 않기 때문에 뇌혈류량이 과소평가 될 수 있다. 이를 보안하기 위하여 Lassen이 linearization algorithm을 만들었다. 그러나 이 방정식은 뇌의 상태에 따라 사용되는 알파값으로 표현되는 변수가 변할 수 있다. 저자들은 뇌경색이 있는 10명의 환자를 대상으로 가장 적절한 ${\alpha}$값을 구하고자 하였다. 재료 및 방법: 10명의 환자들은 모두 0.1에서 10까지의 알파값을 이용하여 교정한 $^{99m}Tc$-HMPAO와 $^{99m}Tc$-ECD 뇌관류 단일광자방출 단층촬영(single photon emission computed tomography: SPECT) 영상을 구하고, 양전자방출단층촬영술로 뇌혈류영상을 구하였다. 그리고 상호정보의 최대화에 의한 multi-modal volume registration을 이용하는 컴퓨터프로그램으로 양전자방출단층촬영술로 구한 뇌혈류와 SPECT 영상에서 다양한 알파값을 대입하여 Lassen의 linearization algorithm으로 구한 뇌혈류값을 픽셀단위로 서로 비교하였다. 결과: Lassen의 linearization algorithm을 이용하여 구한 $^{99m}Tc$-HMPAO와 $^{99m}Tc$-ECD 뇌관류 SPECT의 국소 뇌혈류량은 알파값이 각각 1.4와 2.1일때 양전자방출전산화단층촬영술로 구한 뇌혈류량과의 상관관계가 가장 높았다. 결론: Lassen의 linearization algorithm을 이용하여 뇌혈류량을 정량화하는 경우에는 $^{99m}Tc$-HMPAO의 경우는 1.4, $^{99m}Tc$-ECD의 경우는 2.1을 사용할 때 뇌혈류량을 가장 잘 반영할 것으로 생각된다.