scholarly journals A novel model of ischemia in rats with middle cerebral artery occlusion using a microcatheter and zirconia ball under fluoroscopy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Teppei Komatsu ◽  
Hiroki Ohta ◽  
Haruhiko Motegi ◽  
Junichi Hata ◽  
Koshiro Terawaki ◽  
...  

AbstractThe failure of neuroprotective treatment-related clinical trials may be partially caused by unestablished animal models. Existing animal models are less likely to provide occlusion confined to the middle cerebral artery (MCA), making transarterial intervention difficult. We aimed to develop a novel focal stroke model using a microcatheter and zirconium dioxide that is non-magnetic under fluoroscopic guidance, which can monitor MCA occlusion and can improve hemorrhagic complications. Using male Sprague Dawley rats (n = 10), a microcatheter was navigated from the caudal ventral artery to the left internal carotid artery using an X-ray fluoroscopy to establish local occlusion. All rat cerebral angiographies were successful. No rats had hemorrhagic complications. Eight (80%) rats underwent occlusion of the MCA bifurcation by zirconium dioxide. Accidentally, the left posterior cerebral artery was failure embolized in 2 rats (20%). The median operating time was 8 min. All rats of occlusion MCA revealed an incomplete hemiparesis on the right side with neurological deficit score ranging from 1 to 3 (median 1, interquartile range 1–3) at 24 h after the induction of ischemia. Moreover, 2% 2,3,5-triphenyl tetrazolium chloride staining showed that the median infarct volume (mm3) was 280 (interquartile range 267–333) 24 h after the left MCA bifurcation occlusion. We present a novel rat model for focal stroke using a microcatheter and zirconium dioxide which does not affect the MRI. The model is predictable which is well confined within the territory supplied by the MCA, and reproducibility of this model is 80%. Fluoroscopy was able to identify which the MCA occlusion and model success while creating the model. It permitted exclusion of animals with complications from the experiment.

2021 ◽  
Author(s):  
Teppei Komatsu ◽  
Hiroki Ohta ◽  
Haruhiko Motegi ◽  
Junichi Hata ◽  
Koshiro Terawaki ◽  
...  

Abstract Background and Purpose: The failure of neuroprotective treatment-related clinical trials may be partially caused by unestablished animal models. Existing animal models are less likely to provide occlusion confined to the middle cerebral artery (MCA), making transarterial intervention difficult. We aimed to develop a novel focal stroke model using a microcatheter and zirconium dioxide that is non-magnetic under fluoroscopic guidance, which can monitor MCA occlusion and can improve hemorrhagic complications. Methods: Using male Sprague Dawley rats (n=8), a microcatheter was navigated from the caudal ventral artery to the left internal carotid artery using digital subtraction angiography to establish local occlusion. Results: All rat cerebral angiographies were successful. No rats had hemorrhagic complications. Six (75%) rats underwent occlusion of the MCA bifurcation by zirconium dioxide. Accidentally, the left posterior cerebral artery was failure embolized in 2 rats (25%) via the posterior communicating artery. The median operating time was 8.5 min. Moreover, 2% 2,3,5-triphenyl tetrazolium chloride staining showed that the median infarct volume (mm3) was 280 (interquartile range; 267-333) 24 hours after the left MCA bifurcation occlusion. Conclusions: We present a novel rat model for focal stroke using a microcatheter and zirconium dioxide which does not affect the MRI. The model is predictable and reproducible, which is well confined within the territory supplied by the MCA. Fluoroscopy was able to identify which the MCA occlusion and model success while creating the model. It permitted exclusion of animals with complications from the experiment.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Teppei Komatsu ◽  
Hiroki Ohta ◽  
Naoki Takakura ◽  
Tomomichi Kitagawa ◽  
Junichi Hata ◽  
...  

Introduction: The failure of neuroprotective treatment-related clinical trials may be partially caused by unestablished animal models. We aimed to develop a novel focal stroke model using a cell-implantable radiopaque hydrogel micro fiber. The micro fiber is made of barium alginate hydrogel containing zirconia, and fabricated in a dual coaxial laminar flow microfluidic device. Methods: Using male Sprague Dawley rats (n=10), a catheter (ID 0.42mm, OD 0.55mm) was navigated from the caudal ventral artery to the left internal carotid artery using digital subtraction angiography. A radiopaque hydrogel micro fiber (0.4 mm in diameter, 1 mm in length) was advanced in the catheter by slow injection of heparinized physiological saline to establish local occlusion. 9.4-T MRI and 2% 2,3,5-triphenyl tetrazolium chloride staining were performed 24 hours after the creation of the stroke model. Results: The anterior cerebral artery-middle cerebral artery bifurcation was selectively embolized at all rats. The median operating time was 8.5 min (interquartile range; 6.25-12 min). The median infarct volume (mm 3 ) was 262 (interquartile range; 260-274) 24 hours after occlusion. Conclusions: We present a novel rat model for focal infarct only in the middle cerebral artery territory using a radiopaque hydrogel micro fiber. Furthermore, this model can be used for regeneration research of cerebral infarction because the hydrogel micro fiber can encapsulate stem cell.Figure Legends A: Puncture of the caudal ventral artery in a rat. B: Cerebral angiography of a rat. C: Occlusion of the anterior cerebral artery-middle cerebral artery bifurcation by a radiopaque hydrogel fiber (arrowhead). D: MR angiography detected selective occlusion of left middle cerebral artery. E: T2-weighted image showed infarct only in the middle cerebral artery after 24 hours occlusion. A radiopaque fiber did not affect the 9.4-T MRI. F: Radiopaque hydrogel fiber encapsulated HeLa cells.


Neurosurgery ◽  
1986 ◽  
Vol 18 (4) ◽  
pp. 397-401 ◽  
Author(s):  
Bruce I. Tranmer ◽  
Cordell E. Gross ◽  
Ted S. Keller ◽  
Glenn W. Kindt

Abstract Five consecutive patients with acute neurological deficits after middle cerebral artery (MCA) occlusion were given emergency treatment with colloidal volume expansion. In each case, the diagnosis was confirmed promptly by computed tomography and cerebral angiography. Aggressive volume expansion therapy was started 2 to 18 hours (mean, 11 hr) after the onset of the neurological deficit. The mean colloidal volume used was 920 ml/day for an average of 4 days. During volume expansion, the mean cardiac output increased 57% from 4.6 + 0.6 to 7.2 + 1.9 litres/min (P < 0.05). The mean hematocrit decreased 19% from 46 + 3% to 37 + 4% (P < 0.01). The mean arterial blood pressure remained stable, and the pulmonary artery wedge pressure was maintained at < 15 mm Hg. Three patients improved dramatically with volume expansion therapy and have returned to their previous life-styles. Two patients made partial recoveries and manage at home with nursing care. The three patients who improved dramatically were young (aged <34) and, when compared to the older patients, they had greater increases in cardiac output (67% vs. 19%). No major complications or deaths were attributed to the volume expansion therapy. We propose that intravascular volume expansion and its concomitant augmentation of the cardiovascular dynamics may be effective in the treatment of acute neurological deficits after acute MCA occlusion.


1987 ◽  
Vol 7 (5) ◽  
pp. 557-562 ◽  
Author(s):  
S. Komatsumoto ◽  
S. Nioka ◽  
J. H. Greenberg ◽  
K. Yoshizaki ◽  
V. H. Subramanian ◽  
...  

The energy metabolism of the brain has been measured in a middle cerebral artery (MCA) occlusion model in the cat utilizing 31P-nuclear magnetic resonance (NMR). 31P-NMR spectra were serially obtained during 2 h of ischemia and a subsequent 4-h recovery period. The ratio of creatine phosphate (PCr) to inorganic phosphate (Pi) (PCr/Pi) showed a precipitous decrease in parallel with changes in electroencephalographic (EEG) amplitude in severe strokes during ischemia as well as during recirculation. Animals with mild strokes, as determined by EEG criteria, exhibited a much smaller decrease in PCr/Pi during ischemia. In the severe strokes, there was a splitting and significant shift of the Pi peak immediately after occlusion. In addition, the shifted Pi peak rapidly increased and remained elevated throughout the study. In the mild strokes, Pi also increased, but not as markedly. Intracellular pH determination by chemical shift of the Pi peak revealed a decrease from 7.1 to 6.2–6.3 during ischemia and the subsequent recovery period in the animals with severe strokes, whereas the pH in the animals with mild strokes did not show a significant change. A gradual decrease in adenosine triphosphate (ATP) to 57–79% of the control was exhibited in severely stroked animals during both the ischemia and the recovery period, whereas there was no change in ATP in the mild stroked animals. These results suggest that the dynamic process of pathophysiological changes in an MCA occlusion model in the cat leads to significant differences in cerebral metabolism between animals with mild and severe strokes.


1996 ◽  
Vol 16 (4) ◽  
pp. 599-604 ◽  
Author(s):  
Zheng G. Zhang ◽  
David Reif ◽  
James Macdonald ◽  
Wen Xue Tang ◽  
Dietgard K. Kamp ◽  
...  

We tested the effects of administration of a selective neuronal nitric oxide synthase (nNOS) inhibitor, ARL 17477, on ischemic cell damage and regional cerebral blood flow (rCBF), in rats subjected to transient (2 h) middle cerebral artery (MCA) occlusion and 166 h of reperfusion (n = 48) and in rats without MCA occlusion (n = 25), respectively. Animals were administered ARL 17477 (i.v.): 10 mg/kg; 3 mg/kg; 1 mg/kg; N-nitro-L-arginine (L-NA) 10 mg/kg L-NA 1 mg/kg; and Vehicle. Administration of ARL 17477 1 mg/kg, 3 mg/kg and 10 mg/kg reduced ischemic infarct volume by 53 (p < 0.05), 23, and 6.5%, respectively. L-NA 1 mg/kg and 10 mg/kg increased infarct volume by 2 and 15%, respectively (p > 0.05). Administration of ARL 17477 (10 mg/kg) significantly (p < 0.05) decreased rCBF by 27 ± 5.3 and 24 ± 14.08% and cortical NOS activity by 86 ± 14.9 and 91 ± 8.9% at 10 min or 3 h, respectively, and did not alter mean arterial blood pressure (MABP). L-NA (10 mg/kg) significantly reduced rCBF by 23 ± 9.8% and NOS activity by 81 ± 7% and significantly (p < 0.05) increased MABP. Treatment with 3 mg/kg and 1 mg/kg ARL 17477 reduced rCBF by only 2.4 ± 4.5 and 0%, respectively, even when NOS activity was reduced by 63 ± 13.4 and 45 ± 15.7% at 3 h, respectively, (p < 0.05). The data demonstrate that ARL 17477 inhibits nNOS in the rat brain and causes a dose-dependent reduction in infarct volume after transient MCA occlusion.


1985 ◽  
Vol 62 (6) ◽  
pp. 831-838 ◽  
Author(s):  
Brian T. Andrews ◽  
Norman L. Chater ◽  
Philip R. Weinstein

✓ Forty-seven patients with middle cerebral artery (MCA) stenosis and 18 patients with MCA occlusion underwent extracranial-intracranial arterial bypass procedures. Patients presented with a history of transient ischemic attacks (TIA's), reversible ischemic neurological deficits, TIA's after initial stroke, stroke-in-evolution, or completed stroke. Angiography revealed that the MCA stenosis ranged from 70% to over 95%. Two patients (4.3%) in the stenosis group had a perioperative stroke (within 30 days of operation). There was no perioperative mortality. In the occlusion group, no patient had a perioperative stroke, and one patient (5.5%) died from a non-neurological disease. The TIA's resolved completely in 90% of the patients with stenosis and in 91.6% of those with occlusion. No patient with MCA stenosis had a late ipsilateral stroke, although five had a contralateral or vertebrobasilar stroke. One patient with MCA occlusion had a late ipsilateral stroke. The bypass patency rate at late follow-up review was 100%. The results of intracranial-extracranial arterial bypass procedures appear to be similar for patients with either stenosis or occlusion of the MCA. Symptomatic relief of TIA's was excellent and, in two patients with progressive stroke-in-evolution, the deficit was stabilized. The incidence of postoperative ipsilateral stroke was low in patients with TIA's alone or with TIA's after an initial stroke, but among patients with completed stroke, improvement was confined to slight reduction in the neurological deficit.


1995 ◽  
Vol 15 (6) ◽  
pp. 969-979 ◽  
Author(s):  
Raymond T. Bartus ◽  
Reginald L. Dean ◽  
Kathy Cavanaugh ◽  
David Eveleth ◽  
Debra L. Carriero ◽  
...  

Changes in neocortex and striatum were characterized over time following focal ischemia to the brain. Rats were subjected to permanent middle cerebral artery occlusion (MCA-O) and sacrificed 1, 3, 6, 12, or 24 h later. The affected tissue was processed for tetrazolium chloride (TTC) and cresyl violet staining, as well as for Western blots to detect calpain-induced spectrin proteolysis. Significant changes in cell size and spectrin breakdown occurred within the first hour of occlusion, with further, dramatic changes in these two early markers continuing over time. Initial evidence of cell loss was noted at 1 h postocclusion in the striatum and at 3 h in the neocortex. However, even in the center of the most affected portion of the neocortex, the majority of cells appeared to be intact through 6 h. By this time, a significant TTC-defined infarct also emerged. These quantitative data indicate that calpain-induced proteolysis occurs very soon after the ischemic insult, is correlated with earliest changes in cell hypotrophy, and precedes or occurs in tandem with evidence of significant cell loss. They also demonstrate that, while some cell loss occurs earlier than previously believed, the majority of cells remains morphologically intact well beyond what is typically thought to be the window of opportunity for intervention. The results thus raise the question of how long after the ischemic event pharmaceutic intervention might be employed to salvage substantial numbers of neurons.


2019 ◽  
Vol 25 (6) ◽  
pp. 644-647
Author(s):  
Mohamad Abdalkader ◽  
Christian Raftopoulos ◽  
Patrice Finet ◽  
Thanh N Nguyen ◽  
Pierre Goffette

Cerebral artery fenestrations are rare anatomical variants usually detected incidentally on cross-sectional imaging or cerebral angiography. Although considered benign findings, many reports have described their association with vascular abnormalities such as aneurysms or arteriovenous malformations, and to a lesser extent with ischemic or hemorrhagic complications. We report a case of middle cerebral artery fenestration associated with subarachnoid hemorrhage and middle cerebral artery thrombosis. To our knowledge, there has been no prior report of middle cerebral artery fenestration with a similar presentation.


1988 ◽  
Vol 8 (3) ◽  
pp. 357-366 ◽  
Author(s):  
Hitoshi Nakayama ◽  
W. Dalton Dietrich ◽  
Brant D. Watson ◽  
Raul Busto ◽  
Myron D. Ginsberg

The histopathological and hemodynamic consequences of photochemically induced middle cerebral artery (MCA) thrombosis and recanalization were studied in the rat. Recanalization of the thrombosed MCA segment was achieved by the topical application of nimodipine at 1 h following photochemically induced occlusion. Pathological consequences of permanent and temporary occlusion were compared by morphometric procedures 7 days following thrombus formation. Rats with permanent thrombosis exhibited consistent infarction of both striatum and cortex. MCA recanalization at 1 h was associated with a significant reduction in total infarct volume. In recanalized rats, small cortical infarcts, confined to the peripheral MCA territory, were observed in only three of six rats. In contrast, a mixed pattern of infarction and ischemic cell damage was documented throughout the striatum in all rats. Local CBF (ICBF), measured autoradiographically, was significantly reduced in the MCA territory following 1 h of MCA occlusion, especially within the striatum. At 1 h after recanalization, lCBF recovered within the previously ischemic brain regions to >50% of control. Perfusion deficits were detected by carbon black infusion within focal areas of the striatum following reperfusion. Thus, cortical neurons appear to tolerate 1 h of MCA occlusion in this model. In contrast, reperfusion following 1 h of photochemically induced MCA occlusion gives rise to selective injury to the striatum.


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