• 약학회지
• /
• 제32권5호
• /
• pp.343-350
• /
• 1988

Recent hypothesis suggested that intracellular accumulation of calcium is a common denominator of ischemic celullar damage. Flunarizine, a calcium entry blocker, posses vasodilating properties in cerebral vascular beds and clinically used in circulatory disorders. The present study was designed to evaluate the effect of flunarizine on ischemic and hypoxic brain damage. An ischemic model was made by bilateral carotid artery ligation (BCAL) in Wistar strain rat. Hypoxic model was made by intravenous injection(i.v.) of KCN to rats and mice. In mice, flunarizine not only reduced the mortality of KCN, but also delayed the onset time of convulsion. The contents of ATP, creatine phosphate and glucose, cerebral energy metabolite, decreased 30 minutes after BCAL and KCN i, v, while that of lactate increased. But these variations were suppressed by flunarizine. Furthermore, increase in the dosage of flunarizne generally promoted the recovery of cerebral energy metabolites in hypoxic animals. The results suggest that flunarizine had a protective effect against ischemic and hypoxic brain damage due to its ameliorating action on the cerebral energy metabolism.

• Journal of Korean Neurosurgical Society
• /
• 제39권2호
• /
• pp.130-135
• /
• 2006

Objective : After ischemic stroke, partial recovery of function frequently occurs and may depend on the plasticity of axonal connections. Here, we examine whether blockade of the Nogo/NogoReceptor[NgR] pathway might enhance axonal sprouting and thereby recovery after focal brain infarction. Methods : Adult male Sprague Dawley rats weighing $250{\sim}350g$ were used. Left middle cerebral artery occlusion[MCAO] was induced with a intraluminal filament. An osmotic mini pump [Alzet 2ML4, Alza Scientific Products, Palo Alto, CA] for the infusion of NgR-Ecto[310]-Fc to block Nogo/NgR pathway was implanted 1 week after cerebral ischemia. Prior to induction of ischemia, all animals received training in the staircase and rotarod test. Two weeks after biotin dextran amine injection, animals were perfused transcardially with PBS, followed by 4% paraformadehyde/PBS solution. Brain and cervical spinal cord were dissected. Eight coronal sections spaced at 1mm intervals throughout the forebrain of each animal with cresyl violet acetate for determination of infarction size. Images of each section were digitized and the infarct area per section was measured with image analysis software. Results : Histological examination at 11 weeks post-MCAO demonstrates reproducible stroke lesions and no significant difference in the size of the stroke between the NgR[310]Ecto-Fc protein treated group and the control group. Behavioral recovery is significantly better and more rapid in the NgR-Ecto[310]-Fe treated group. Blockade of NgR enhances axonal sprouting from the uninjured cerebral cortex and improves the return of motor task performance. Conclusion : Pharmacological interruption of NgR allows a greater degree of axonal plasticity in response this is associated with improved functional recovery of complicated motor tasks.

• 한방재활의학과학회지
• /
• 제18권2호
• /
• pp.33-43
• /
• 2008

Objectives : Sunghyangjungki-san(Xingxiangzhengqi-san) is a herb decoction prescribed frequently for stroke patients. The present study investigated neuroprotective effects of Sunghyangjungki-san(Xingxiangzhengqi-san) against the ischemic damage of the rat brain. Neuronal cell death under the cerebral ischemia is distinguished with the delayed cell death through apoptosis. Consequently, the effects of Sunghyangjungki-san(Xingxiangzhengqi-san) was evaluated with Bax and Bcl-2 expressions as apoptosis related factors in the brain tissues. Methods : The ischemic damage was induced by the middle cerebral artery occlusion(MCAO) method in Sprague-Dawley rats. Water extract of Sunghyangjungki-san(Xingxiangzhengqi-san) was treated for 5 days after the MCAO. Neurological scores and infarct size with TTC were measured. Bax and Bcl-2 expressions in the brain tissues were observed with immunohistochemistry. Results : Sunghyangjungki-san(Xingxiangzhengqi-san) treatment improved neurological score significantly at 5 days after the MCAO. Sunghyangjungki-san(Xingxiangzhengqi-san) treatment decreased infarct size by the MCAO, but it was not significant statistically. Sunghyangjungki-san(Xingxiangzhengqi-san) treatment attenuated Bax positive neurons significantly in the cerebral penumbra and the caudate putamen. Bcl-2 positive neurons were increased, but not significant. Sunghyangjungki-san(Xingxiangzhengqi-san) treatment increased Bcl-2/Bax expression ratios significantly in the cerebral penumbra and the caudate putamen. Conclusions : These results suggest that Sunghyangjungki-san(Xingxiangzhengqi-san) has a neuroprotective effect on the stroke with modulation of apoptosis related factors.

• The Journal of Korean Physical Therapy
• /
• 제15권4호
• /
• pp.199-207
• /
• 2003

신생아의 정상적인 발달을 저해하고 조기 사망의 주된 원인이 되고 있는 주산기 뇌손상에 관한 신경병리적 기전을 살펴보고자 하였다. 발달하고 있는 과정에서의 주산기 뇌손상은 주로 저산소성-허혈성 뇌손상과 출혈성 뇌손상에 의한 경우가 많다. 저산소성-허혈성 뇌손상과 관련하여 에너지 부전, 세포흥분독성, 미성숙 백질의 선택적 취약성을 고려해 볼 수 있다. 첫번째, 세포호흡에 관여하는 미토콘드리아의 손상과 관련하여 즉각적인 병리와 함께 지연된 양상의 손상을 보인다. 미토콘드리아의 호흡률이 감소하고 칼슘이온의 농도가 상승하여 세포 괴사 및 세포사멸 과정이 진행된다. 두번째, 흥분성 아미노산과 관련하여 미성숙한 뇌에는 NMDA 수용기-채널 복합체의 기능이 매우 풍부하고, phosphoinositide 가수분해가 높아서 흥분독성에 상당히 취약하다. 세 번째, 수초 형성에 중요한 역할을 하는 희돌기교세포가 주산기 뇌손상 특히, 저산소성-허혈성 손상에 취약하다. 희돌기교세포는 글루타메이트에 의한 자유유리기과 사이토카인 손상에 취약하다. 뇌출혈과 관련하여, 미성숙한 뇌는 뇌실 주위에 혈관층이 풍부하나 매우 약한 상태로 재관류 혹은 혈류의 증가로 인해 쉽게 파열된다. 특히 32주 이내인 경우 이러한 손상으로 인해 뇌실주위 백질연화증이 초래된다.

• Journal of Korean Neurosurgical Society
• /
• 제38권6호
• /
• pp.431-434
• /
• 2005

Objective : Subarachnoid hemorrhage[SAH] is commonly associated with polyuria [solute diuresis or water diuresis]. The authors investigate the incidence and clinical characteristics of polyuria with special reference to the administration of osmotic diuretics. Methods : One hundred and forty eight patients with high urine output [>200ml/hr] after ruptured cerebral aneurysm operated early from Jan 1998 to Jun 2003 were selected. Water diuresis [diabetes insipidus, DI] was differentiated from solute diuresis by lower urine specific gravity [<1.005] and higher plasma osmolality. The incidence and mode of onset of polyuria were compared between two types of diuresis. Additionally, the relationships between development of polyuria and clinical features including aneurysm location, clinical grade, Fisher grade, and outcome were analyzed. Osmotic diuretics were not routinely used in patients with Hunt-Hess grade I-III since July 2001. Results : Annual incidence of polyuria decreased markedly since July 2001 : 45.2% in 1998, 34.5% in 2001, 11.9% in 2003. Postoperative DI occurred in $2.4{\sim}11.1%$. DI developed mainly from ruptured anterior communicating artery aneurysm. The mean interval between the last SAH and the onset of DI was 7.1 days [range $1{\sim}27$ days] and lasted mean 4.6 days. When compared with solute diuresis, the development of DI was significantly delayed. Other clinical features were not closely related to polyuria. Conclusion : Uncontrolled polyuria may lead to cerebral ischemia and electrolyte imbalance because SAH patients are already predisposed to hypovolemia, and will risk precipitating the opposite situation with overhydration. We can decrease the development of polyuria without routine use of osmotic diuretics, by avoiding the increased intracranial pressure such as the intraoperative ventriculostomy and gentle brain retraction in good grade patients.

• 대한한방내과학회지
• /
• 제22권2호
• /
• pp.145-160
• /
• 2001

Objectives : The purpose of this investigation is to evaluate the effect of Geupoongjibo-dan Extracts on Reversible Forebrain Ischemia in Mongolian Gerbils. Methods : The change rate of water content in cerebral tissues, the numercal change of the CA1 pyramidal neuron in the hippocampus, the change of delayed neuronal death(necrosis apoptosis) through light microscopy, the reactivity change of glycoprotein in neuronal membrane and the ultrastructural change of pyramidal neuron through electron microscopy caused by dalayed neuronal death were investigated. Results : 1. The change rate of water content in the normal group showed 78.90% on the third day, and 79.12% on the seventh day after an attack of ischemia. The rate in the control group showed 82.25% and 85.13%, respectively. The rate in the sample group showed a significant decrease: 81.72% and 83.66%. 2. Light microscopy revealed that the cells, continuous and systematic forms in the pyramidal cells of hippocampus, changed into discontinuous and unsystematic forms in the normal group when compared with the control group. The cells were less damaged in the sample group. 3. The mean of the numerical change of the CA1 pyramidal neurons in the hippocampus was 104 in the normal group. The mean of the control group was decreased to 27. The mean of the sample group was 44. 4. TUNEL staining examination reveals that the whole part of the hippocampus of the normal group had negative reactivity. As far as CA1 pyramidal neurons in the hippocampus, the control group had positive reactivity. The sample group was more positive than the control group. 5. Electron microscopy reveals that the ischemic injury of the control group had both necrotic and apoptotic morphology. The sample group was less necrotic, and more apoptotic morphology than the control group. 6. Lectin histochemisrical examination reveals that the normal group had positive reactivity to PNA and SBA in interneuron, and weak positive reactivity to WGA Con A LCA in intercelluar space. The reactivity to PNA and WGA decreased in the control group. The reactivity to PNA and WGA tended to increase in the sample group. Conclusions : The data shows that the effect of Geupoongjibo-dan Extracts on Reversible Forebrain Ischemia in MG is a significant result.

• 약학회지
• /
• 제45권4호
• /
• pp.419-425
• /
• 2001

The neuronal cell death induced by excess glutamate (Glu) has been implicated in many acute and chronic neurodegenerative diseases including cerebral ischemia. Glu-induced elevation of intra-cellular $Ca^{2+}$ plays a critical role in the excitotoxicity, partly through the activation of a variety of $Ca^{2+}$ dependent enzymes. In the present study, we investigated the Glu-induced modulation of $Ca^{2+}$/calmodulin-dependent protein kinase IV (CaMK IV), a multifunctional enzyme abundantly present in the nuclei of neurons. The exposure of cultured rat cortical neurons to $100{\mu}$M Glu for 3 min dramatically increased CaMK IV activity up to 4.5-fold of the control-treated enzyme activity. The activation was very rapid, reaching peak at 3 min and then declined gradually. Under the same experimental conditions, time-dependent acute and delayed neuronal cell death was observed. Immunoblot analyses using specific antibodies showed that the expressions of CaMK IV and $CaMKK_{\alpha}$ were time-dependently modulated by Glu. Taken together, these results imply that the modulation of CaMK IV activity by Glu may be involved in the cascade of events resulting in neuronal cell death in cortical cultures.

• Investigative Magnetic Resonance Imaging
• /
• 제22권2호
• /
• pp.131-134
• /
• 2018

Susceptibility-weighted imaging (SWI) is well known for detecting the presence of hemorrhagic transformation, microbleeds and the susceptibility of vessel signs in acute ischemic stroke. But in some cases, it can provide the tissue perfusion state as well. We describe a case of a patient with hyperacute ischemic infarction that had a slightly hypodense, patchy lesion at the left thalamus on the initial SWI, with a left proximal posterior cerebral artery occlusion on a magnetic resonance (MR) angiography and delayed time-to-peak on an MR perfusion performed two hours after symptom onset. No obvious abnormal signals at any intensity were found on the initial diffusion-weighted imaging (DWI). On a follow-up MR image (MRI), an acute ischemic infarction was seen on DWI, which is the same location as the lesion on SWI. The hypointensity on the initial SWI reflects the susceptibility artifact caused by an increased deoxyhemoglobin in the affected tissue and vessels, which reflects the hypoperfusion state due to decreasing arterial flow. It precedes the signal change on DWI that reflects a cytotoxic edema. This case highlights that, in some hyperacute stages of ischemic stroke, hypointensity on an SWI may be a finding before the hyperintensity is seen on a DWI.

• Journal of Korean Neurosurgical Society
• /
• 제64권1호
• /
• pp.23-29
• /
• 2021

Objective : Although stent-assisted coiling (SAC) has been reported to be safe and effective in treating wide-necked aneurysms, the technique has procedure-related complications. Thus, we reported our experiences of SAC using the Neuroform Atlas stent in treating wide-necked aneurysms and evaluated the incidence of and risk factors for procedure-related complications. Methods : From March 2018 to August 2019, we treated 130 unruptured wide-necked aneurysms in 123 patients with Neuroform Atlas stents. Angiographic results and clinical outcomes were reviewed retrospectively. Clinical and angiographic follow-up were performed in all cases (mean, 12.4 months) after the procedure. Results : There were eight cases (6.2%) of procedure-related complications (two dissections, five thromboembolisms, and one hemorrhage) and two (1.5%) of delayed complications (one ischemia and one hemorrhage). There was one case (0.8%) of failure of stent deployment and one (0.8%) of suboptimal positioning of the stent. Follow-up angiography showed complete obliteration in 103 (79.2%), residual neck in 16 (12.3%), and residual aneurysm in 11 cases (8.5%). Aneurysm locations in the middle cerebral artery (odds ratio [OR], 2.211; p=0.046) and the anterior communicating artery (OR, 2.850; p=0.039) were associated with procedure-related complications on univariate analysis. However, no independent risk factor for procedure-related complications was noted in multivariate analysis. Conclusion : The Neuroform Atlas showed a high rate of technical success. Good clinical and radiographic outcomes in early follow-up suggests that the device is feasible and safe. SAC of aneurysms on the middle cerebral artery or anterior communicating artery may require more attention to prevent possible procedure-related complications.

• Journal of Korean Neurosurgical Society
• /
• 제66권6호
• /
• pp.681-689
• /
• 2023

Objective : Subarachnoid hemorrhage (SAH) is a condition characterized by bleeding in the subarachnoid space, often resulting from the rupture of a cerebral aneurysm. Delayed cerebral ischemia caused by vasospasm is a significant cause of mortality and morbidity in SAH patients, and inflammatory markers such as systemic inflammatory response index (SIRI), systemic inflammatory index (SII), neutrophil-to-lymphocyte ratio (NLR), and derived NLR (dNLR) have shown potential in predicting clinical vasospasm and outcomes in SAH patients. This article aims to investigate the relationship between inflammatory markers and cerebral vasospasm after aneurysmatic SAH (aSAH) and evaluate the predictive value of various indices, including SIRI, SII, NLR, and dNLR, in predicting clinical vasospasm. Methods : A retrospective analysis was performed on a cohort of 96 patients who met the inclusion criteria out of a total of 139 patients admitted Trakya University Hospital with a confirmed diagnosis of aSAH between January 2013 and December 2021. Diagnostic procedures, neurological examinations, and laboratory tests were performed to assess the patients' condition. The Student's t-test compared age variables, while the chi-square test compared categorical variables between the non-vasospasm (NVS) and vasospasm (VS) groups. Receiver operating characteristic (ROC) curve analyses were used to evaluate the diagnostic accuracy of laboratory parameters, calculating the area under the ROC curve, cut-off values, sensitivity, and specificity. A significance level of p<0.05 was considered statistically significant. Results : The study included 96 patients divided into two groups : NVS and VS. Various laboratory parameters, such as NLR, SII, and dNLR, were measured daily for 15 days, and statistically significant differences were found in NLR on 7 days, with specific cut-off values identified for each day. SII showed a significant difference on day 9, while dNLR had significant differences on days 2, 4, and 9. Graphs depicting the values of these markers for each day are provided. Conclusion : Neuroinflammatory biomarkers, when used alongside radiology and scoring scales, can aid in predicting prognosis, determining severity and treatment decisions for aSAH, and further studies with larger patient groups are needed to gain more insights.