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A Simple Method for Predicting Hippocampal Neurodegeneration in a Mouse Model of Transient Global Forebrain Ischemia

  • Cho, Kyung-Ok;Kim, Seul-Ki;Cho, Young-Jin;Sung, Ki-Wug;Kim, Seong Yun
    • The Korean Journal of Physiology and Pharmacology
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    • v.10 no.4
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    • pp.167-172
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    • 2006
  • In the present study, we developed a simple method to predict the neuronal cell death in the mouse hippocampus and striatum following transient global forebrain ischemia by evaluating both cerebral blood flow and the plasticity of the posterior communicating artery (PcomA). Male C57BL/6 mice were anesthetized with halothane and subjected to bilateral occlusion of the common carotid artery (BCCAO) for 30 min. The regional cerebral blood flow (rCBF) was measured by laser Doppler flowmetry. The plasticity of PcomA was visualized by intravascular perfusion of India ink solution. When animals had the residual cortical microperfusion less than 15% as well as the smaller PcomA whose diameter was less than one third compared with that of basilar artery, neuronal damage in the hippocampal subfields including CA1, CA2, and CA4, and in the striatum was consistently observed. Especially, when mice met these two criteria, marked neuronal damage was observed in CA2 subfield of the hippocampus. In contrast, after transient BCCAO, neuronal damage was consistently produced in the striatum, dependent more on the degree of rCBF reduction than on the plasticity of PcomA. The present study provided simple and highly reproducible criteria to induce the neuronal cell death in the vulnerable mice brain areas including the hippocampus and striatum after transient global forebrain ischemia.

The neuroprotective mechanism of ampicillin in a mouse model of transient forebrain ischemia

  • Lee, Kyung-Eon;Cho, Kyung-Ok;Choi, Yun-Sik;Kim, Seong Yun
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.2
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    • pp.185-192
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    • 2016
  • Ampicillin, a ${\beta}$-lactam antibiotic, dose-dependently protects neurons against ischemic brain injury. The present study was performed to investigate the neuroprotective mechanism of ampicillin in a mouse model of transient global forebrain ischemia. Male C57BL/6 mice were anesthetized with halothane and subjected to bilateral common carotid artery occlusion for 40 min. Before transient forebrain ischemia, ampicillin (200 mg/kg, intraperitoneally [i.p.]) or penicillin G (6,000 U/kg or 20,000 U/kg, i.p.) was administered daily for 5 days. The pretreatment with ampicillin but not with penicillin G significantly attenuated neuronal damage in the hippocampal CA1 subfield. Mechanistically, the increased activity of matrix metalloproteinases (MMPs) following forebrain ischemia was also attenuated by ampicillin treatment. In addition, the ampicillin treatment reversed increased immunoreactivities to glial fibrillary acidic protein and isolectin B4, markers of astrocytes and microglia, respectively. Furthermore, the ampicillin treatment significantly increased the level of glutamate transporter-1, and dihydrokainic acid (DHK, 10 mg/kg, i.p.), an inhibitor of glutamate transporter-1 (GLT-1), reversed the neuroprotective effect of ampicillin. Taken together, these data indicate that ampicillin provides neuroprotection against ischemia-reperfusion brain injury, possibly through inducing the GLT-1 protein and inhibiting the activity of MMP in the mouse hippocampus.

Change in Pulpal Blood Flow of Heat-induced Neurogenic Inflammation in Feline Dental Plup (고양이 치수에서 열 자극으로 유도된 신경병증 염증에서 치수 혈류량 변화)

  • Park, Min-Kyoung
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.14 no.12
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    • pp.6340-6345
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    • 2013
  • This study examined the involvement of histamine in heat-induced changes in pulpal blood flow(PBF) to determine the mechanism of neurogenic inflammation in feline dental pulp. The experiments were carried out in 10 felines anesthetized with sodium pentobartial and histamine injected into the dental pulp through the external carotid artery. The change in the pulpal PBF was measured using a laser Doppler flowmeter(Periflux 4001, Stockholm, Sweden). The probe of laser Doppler flowmeter was placed on the buccal surface of the ipsilateral canine teeth. Heat was applied to the tooth using a heat stimulator controlled script file with an input/output device. The application of heat ($40-65^{\circ}C$) induced a significant increase in PBF. The application of histamine($5{\mu}g/kg/1ml$) followed by heat($45^{\circ}C$) resulted in an increase in PBF. Therefore, the results of the present study showed that heat and histamine are capable of vasoconstriction caused by neurogenic inflammation in feline dental pulp. In addition, neurogenic inflammation plays an active role in modulating the microcirculation of the dental pulp.

Analysis of Clip-induced Ischemic Complication of Anterior Choroidal Artery Aneurysms

  • Cho, Min-Soo;Kim, Min-Su;Chang, Chul-Hoon;Kim, Sang-Woo;Kim, Seong-Ho;Choi, Byung-Yon
    • Journal of Korean Neurosurgical Society
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    • v.43 no.3
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    • pp.131-134
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    • 2008
  • Objective: The surgical approach for anterior choroidal artery (AChA) aneurysm is typically similar to those used for other supraclinoid internal carotid artery (ICA) lesions. However, the surgical clipping of this aneurysm is complicated and as a result. can result in postoperative ischemic complications. The purpose of this study was to clarify the risk of clip-induced ischemic complication in AChA aneurysm and to get the benefits for helping decision making. Methods: We retrospectively investigated 53 cases (4.0%) of AchA aneurysm treated surgically. We divided the AChA aneurysm to 3 subtype according to the origin of aneurysmal neck; A type originating from the AChA itself. J type from junction of AChA and ICA and I type from the ICA itself. We evaluated brain CT about 1 week post-operative day to confirm the low density in AChA territory. Results: Ruptured aneurysm was 26 cases and unruptured aneurysm 27 cases. The aneurysmal subtype of A, J, and I was 13, 17, and 23 cases. Of the 53 cases who performed surgical neck clipping, twelve (22.6%) had postoperative AChA distribution infarcts. Increased infarct after neck clipping had statistic significance in non-I subtype (r=0.005) Conclusion: AChA aneurysm surgery carries a significant risk of postoperative stroke. Don't always stick to clipping only, especially in non-I type of incidental small aneurysm, which has high risk of post-clip ischemic complications.

Multimodal Treatment for Complex Intracranial Aneurysms : Clinical Research

  • Jin, Sung-Chul;Kwon, Do-Hoon;Song, Young;Kim, Hyun-Jung;Ahn, Jae-Seung;Kwun, Byung-Duk
    • Journal of Korean Neurosurgical Society
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    • v.44 no.5
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    • pp.314-319
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    • 2008
  • Objective: For patients with giant or dissecting aneurysm, multimodal treatment consisting extracranial-intracranial bypass surgery plus clip or coil for parent artery occlusion may be necessary. In this study, the safety and efficacy of multimodal treatment in 15 patients with complex aneurysms were evaluated retrospectively. Methods: From January 1995 to June 2007, the authors treated 15 complex aneurysms that were unable to be clipped or coiled. Among them, nine patitents had unruptured aneurysms and 6 had ruptured aneurysms. Aneurysms were located in the internal cerebral artery (ICA) in 11 patients (4 in the dorsal wall. 4 in the terminal ICA, 1 in the paraclinoid, and 2 in the cavernous ICA), in the middle cerebral artery (MCA) in 2, and in the posterior circulation in two patients Results: Fifteen patients with complex aneurysms were treated with bypass surgery previously. Thirteen patients were treated with external carotid middle cerebral artery (ECA-MCA) anastomosis, and one patient with superficial temporal to posterior cerebral artery (STA-PCA) and another patient with occipital artery to posterior inferior cerebellar artery (OA-PICA) anastomosis. Parent artery occlusion was then performed with a clip in 9 patients, with a coil in 4, with balloon plus coil in one patient. All 15 aneurysms were successfully treated with clip or coil combined with bypass surgery. Follow-up angiograms showed good patency of anastomotic site in 10 out of 11 patients, and perfusion study showed sufficient perfusion in 6 out of 9 patients. Conclusion: These findings indicate that for patients with complex aneurysms, clip or coil for parent vessel occlusion with additive bypass surgery can successfully exclude the aneurysm from the neurovascular circulatory system.

Mortality and Morbidity of Aneurysmal Neck Clipping during the Learning Curve

  • Lee, Sang-Ho;Hwang, Hyung-Sik;Moon, Seung-Myung;Kim, Sung-Min;Choi, Sun-Kil
    • Journal of Korean Neurosurgical Society
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    • v.40 no.1
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    • pp.16-21
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    • 2006
  • Objective : Young neurosurgeons need to focus on the mortality and morbidity of aneurysmal neck clipping to develop a personal experience with an initial series. Methods : Total 88 aneurysms from 75 patients who underwent neck clipping by the same operator from 2001 to 2004 were reviewed. Patients were divided into three groups : first year [Group I], second year [Group II], and third year [Group III] in each group. Location of aneurysm, age, Fisher grade, Hunter-Hess grade [H-H grade], postoperative Glasgow outcome scale [GOS], and complications related to surgical procedures were evaluated with Chi-square and logistic regression analyses. Results : Fourteen patients had complications related to surgery [18.7%]. The major causes of mortality and morbidity related to surgery were cerebral infarction, hemorrhage and brain swelling due to intraoperative rupture, brain retraction and vasospasm. Among the 4 cases of mortality were 2 patients in Group I, 1 patient in Group II and 1 patient in Group III, and location of aneurysms were 2 internal carotid artery[ICA] and 2 posterior communicating artery[PCoA] aneurysms. There were 4 morbidity and new neurological deficits in Group I, 4 in Group II and 2 in Group III. Although mortality and morbidity during the learning curve had a statistical significance in H-H grade, age [>60 years old], and aneurysm location [especially ICA aneurysm] as variables, mortality mainly occurred in ICA and PCoA aneurysms. Conclusion : Experienced supervision or endovascular approach should be considered for the treatment of ICA and PCoA aneurysms during the learning curve.

Determination of Aneurysmal Location with 3 Dimension-Computed Tomographic Angiography in the Microsurgery of Paraclinoid Aneurysms

  • Kim, Min-Young;Chung, Seung-Young;Kim, Seung-Min;Park, Moon-Sun;Jung, Sung-Sam
    • Journal of Korean Neurosurgical Society
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    • v.42 no.1
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    • pp.35-41
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    • 2007
  • Objective : Determining the location of paraclinoid aneurysms for microsurgery is important for selecting treatment options, especially when deciding on the release of the dural ring in direct clipping. We examined the reliability of using the optic strut as an anatomical landmark for evaluating the location of paraclinoid aneurysms. Methods : Cadaveric dissection was performed to establish the relationship of the optic strut to the dural ring. Results from these anatomic studies were compared with the three-demensional computed tomographic angiographic [3D-CTA] findings of nine patients with ten paraclinoid aneurysms between May 2004 and October 2005. These, 3D-CTA results were then compared with intraoperative findings. Results : The inferior boundary of the optic strut accurately localized the point at the proximal dural ring in cadaveric study. The optic strut and its relationship to the aneurysms was well observed on the multiplanar reformats of 3D-CTA. During microsurgery, nine of ten aneurysms were verified to arise from distal to the upper surface of the optic strut. Two aneurysms that had arisen between the inferior and superior boundary of the optic strut were observed to lie within the carotid cave. One aneurysm which had arisen at the inferior boundary of the optic strut and directed inferiorly was observed to lie within the cavernous sinus just after the release of the proximal ring. Conclusion : The optic strut, as identified with multiplanar reformats of 3D-CTA, provided a reliable anatomic landmark for the proximal rings and an important information about the location of aneurysms around the anterior clinoid process (ACP). Therefore, 3D-CTA and the optic strut could become an invaluable tool and a landmark in the assessment of the location of paraclinoid aneurysms for microsurgery.

Neuroprotective Effect of Resveratrol on Acute Brain Ischemia Reperfusion Injury by Measuring Annexin V, p53, Bcl-2 Levels in Rats

  • Kizmazoglu, Ceren;Aydin, Hasan Emre;Sevin, Ismail Ertan;Kalemci, Orhan;Yuceer, Nurullah;Atasoy, Metin Ant
    • Journal of Korean Neurosurgical Society
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    • v.58 no.6
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    • pp.508-512
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    • 2015
  • Background : Cerebral ischemia is as a result of insufficient cerebral blood flow for cerebral metabolic functions. Resveratrol is a natural phytoalexin that can be extracted from grape's skin and had potent role in treating the cerebral ischemia. Apoptosis, a genetically programmed cellular event which occurs after ischemia and leads to biochemical and morphological changes in cells. There are some useful markers for apoptosis like Bcl-2, bax, and p53. The last reports, researchers verify the apoptosis with early markers like Annexin V. Methods : We preferred in this experimental study a model of global cerebral infarction which was induced by bilateral common carotid artery occlusion method. Rats were randomly divided into 4 groups : sham, ischemia-reperfusion (I/R), I/R plus 20 mg/kg resveratrol and I/R plus 40 mg/kg resveratrol. Statistical analysis was performed using Sigmastat 3.5 ve IBM SPSS Statistics 20. We considered a result significant when p<0.001. Results : After administration of resveratrol, Bcl-2 and Annexin levels were significantly increased (p<0.001). Depending on the dose of resveratrol, Bcl2 levels increased, p53 levels decreased but Annexin V did not effected. P53 levels were significantly increased in ishemia group, so apoptosis is higher compared to other groups. Conclusion : In the acute period, Annexin V levels misleading us because the apoptotic cell counts could not reach a certain level. Therefore we should support our results with bcl-2 and p53.

Morphometric Study of the Anterior Thalamoperforating Arteries

  • Kim, Sung-Ho;Yeo, Dong-Kyu;Shim, Jae-Joon;Yoon, Seok-Mann;Chang, Jae-Chil;Bae, Hack-Gun
    • Journal of Korean Neurosurgical Society
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    • v.57 no.5
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    • pp.350-358
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    • 2015
  • Objective : To evaluate the morphometry of the anterior thalamoperforating arteries (ATPA). Methods : A microanatomical study was performed in 79 specimens from 42 formalin-fixed adult cadaver brains. The origins of the ATPAs were divided into anterior, middle, and posterior segments according to the crowding pattern. The morphometry of the ATPAs, including the premammillary artery (PMA), were examined under a surgical microscope. Results : The anterior and middle segments of the ATPAs arose at mean intervals of $1.75{\pm}1.62$ mm and $5.86{\pm}2.05$ mm from the internal carotid artery (ICA), and the interval between these segments was a mean of $3.17{\pm}1.64$ mm. The posterior segment arose at a mean interval of $2.43{\pm}1.46$ mm from the posterior cerebral artery (PCA), and the interval between the middle and posterior segments was a mean of $3.45{\pm}1.39$ mm. The mean numbers of perforators were $2.66{\pm}1.19$, $3.03{\pm}1.84$, and $1.67{\pm}0.98$ in the anterior, middle, and posterior segments, respectively. The PMA originated from the middle segment in 66% of cases. A perforator-free zone was located >2 mm from the ICA in 30.4% and >2 mm from the PCA in 67.1% of cases. Conclusion : Most perforators arose from the anterior and middle segments, within the anterior two-thirds of the posterior communicating artery (PCoA). The safest perforator-free zone was located closest to the PCA. These anatomical findings may be helpful to verify safety when treating lesions around the PCoA and in the interpeduncular fossa.

The Avoidance of Microsurgical Complications in the Extradural Anterior Clinoidectomy to Paraclinoid Aneurysms

  • Son, Hee-Eon;Park, Moon-Sun;Kim, Seong-Min;Jung, Sung-Sam;Park, Ki-Seok;Chung, Seung-Young
    • Journal of Korean Neurosurgical Society
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    • v.48 no.3
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    • pp.199-206
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    • 2010
  • Objective : Paraclinoid segment internal carotid artery (ICA) aneurysms have historically been a technical challenge for neurovascular surgeons. The development of microsurgical approach, advances in surgical techniques, and endovascular procedures have improved the outcome for paraclinoid aneurysms. However, many authors have reported high complication rates from microsurgical treatments. Therefore, the present study reviews the microsurgical complications of the extradural anterior clinoidectomy for treating paraclinoid aneurysms and investigates the prevention and management of observed complications. Methods : Between January 2004 and April 2008, 22 patients with 24 paraclinoid aneurysms underwent microsurgical direct clipping by a cerebrovascular team at a regional neurosurgical center. Microsurgery was performed via an ipsilateral pterional approach with extradural anterior clinoidectomy. We retrospectively reviewed patients' medical charts, office records, radiographic studies, and operative records. Results : In our series, the clinical outcomes after an ipsilateral pterional approach with extradural anterior clinoidectomy for paraclinoid aneurysms were excellent or good (Glasgows Outcome Scale : GOS 5 or 4) in 87.5% of cases. The microsurgical complications related directly to the extradural anterior clinoidectomy included transient cranial nerve palsy (6), cerebrospinal fluid leak (1), worsened change in vision (1), unplanned ICA occlusion (1), and epidural hematoma (1). Only one of the complications resulted in permanent morbidity (4.2%), and none resulted in death. Conclusion : Although surgical complications are still reported to occur more frequently for the treatment of paraclinoid aneurysms, the permanent morbidity and mortality resulting from a extradural anterior clinoidectomy in our series were lower than previously reported. Precise anatomical knowledge combined with several microsurgical tactics can help to achieve good outcomes with minimal complications.