Comparative neuroprotective efficacy of prolonged moderate intraischemic and postischemic hypothermia in focal cerebral ischemia

1999 ◽  
Vol 7 (5) ◽  
pp. E2 ◽  
Author(s):  
Pil W. Huh ◽  
Ludmila Belayev ◽  
Weizhao Zhao ◽  
Sebastian Koch ◽  
Raul Busto ◽  
...  

Object The purpose of this study was to compare the effects of prolonged hypothermia on ischemic injury in a highly reproducible model of middle cerebral artery (MCA) occlusion in rats. Methods Male Sprague-Dawley rats were anesthetized with halothane and subjected to 120 minutes of temporary MCA occlusion by retrograde insertion of an intraluminal nylon suture coated with poly-L-lysine through the external carotid artery into the internal carotid artery and the MCA. Two levels of prolonged postischemic cranial hypothermia (32°C and 27°C), and one level of intraischemic cranial hypothermia (32°C) were compared with the ischemic normothermia (37°C) condition. Target cranial temperatures were maintained for 3 hours and then gradually restored to 35°C over an additional 2-hour period. The animals were evaluated using a quantitative neurobehavioral battery of tests before inducing MCA occlusion, during occlusion (at 60 minutes postonset in all rats except those in the intraischemic hypothermia group), and at 24, 48, and 72 hours after reperfusion. The rat brains were perfusion fixed at 72 hours after ischemia and infarct volumes and brain edema were determined. Both intraischemic and postischemic cooling to 32°C led to similar significant reductions in cortical infarct volume (by 89 and 88%, respectively) and total infarct volume (by 54 and 69%, respectively), whereas postischemic cooling to 27°C produced lesser reductions (64 and 49%, respectively), which were not statistically significant. All three hypothermic regimens significantly lessened hemispheric swelling and improved the neurological score at 24 hours. Our data confirm that a high degree of histological neuroprotection is conferred by postischemic cooling to 32°C, which is virtually equivalent to that observed with intraischemic cooling to the same level. Conclusions These results may be relevant to the design of future clinical trials of therapeutic hypothermia for acute ischemic stroke.

2000 ◽  
Vol 92 (1) ◽  
pp. 91-99 ◽  
Author(s):  
Pil W. Huh ◽  
Ludmila Belayev ◽  
Weizhao Zhao ◽  
Sebastian Koch ◽  
Raul Busto ◽  
...  

Object. The purpose of this study was to compare the effects of prolonged hypothermia on ischemic injury in a highly reproducible model of middle cerebral artery (MCA) occlusion in rats.Methods. Male Sprague—Dawley rats were anesthetized with halothane and subjected to 120 minutes of temporary MCA occlusion by retrograde insertion of an intraluminal nylon suture coated with poly-l-lysine through the external carotid artery into the internal carotid artery and the MCA. Two levels of prolonged postischemic cranial hypothermia (32°C and 27°C) and one level of intraischemic cranial hypothermia (32°C) were compared with the ischemic normothermia (37°C) condition. Target cranial temperatures were maintained for 3 hours and then gradually restored to 35°C over an additional 2-hour period. The animals were evaluated using a quantitative neurobehavioral battery of tests before inducing MCA occlusion, during occlusion (at 60 minutes postonset in all rats except those in the intraischemic hypothermia group), and at 24, 48, and 72 hours after reperfusion. The rat brains were perfusion fixed at 72 hours after ischemia, and infarct volumes and brain edema were determined. Both intraischemic and postischemic cooling to 32°C led to similar significant reductions in cortical infarct volume (by 89% and 88%, respectively) and total infarct volume (by 54% and 69%, respectively), whereas postischemic cooling to 27°C produced lesser reductions (64% and 49%, respectively), which were not statistically significant. All three hypothermic regimens significantly lessened hemispheric swelling and improved the neurological score at 24 hours. The authors' data confirm that a high degree of histological neuroprotection is conferred by postischemic cooling to 32°C, which is virtually equivalent to that observed with intraischemic cooling to the same level.Conclusions. These results may be relevant to the design of future clinical trials of therapeutic hypothermia for acute ischemic stroke.


1988 ◽  
Vol 8 (1) ◽  
pp. 116-120 ◽  
Author(s):  
Stephen C. Saris ◽  
Donald C. Wright ◽  
Edward H. Oldfield ◽  
Ronald G. Blasberg

Intracarotid artery infusions in animals are commonly performed in studies of the blood–brain barrier and in chemotherapy trials. Implicit in the analysis of these experiments is that the infusate will be distributed to the territory of the internal carotid artery in a manner that is proportional to blood flow. Fifteen Sprague-Dawley rats were studied to determine if poor infusate mixing with blood due to intravascular streaming occurred during intracarotid artery drug infusions and if it could be eliminated with fast retrograde infusion. In three experimental groups, a radiolabeled flow tracer—14C-iodoantipyrine (IAP)—was infused retrograde through the external carotid artery into the common carotid artery at slow, medium, and fast rates (0.45, 1.5, and 5.0 ml/min). In a control group, IAP was injected intravenously (i.v.). Local isotope concentrations in the brain were determined by quantitative autoradiography, and the variability of isotope delivery was assessed in the frontoparietal cortex, temporal cortex, and caudate putamen of all animals. Streaming phenomena were manifest in all selected anatomic areas after the slow and medium rates of intraarterial infusion. After fast intracarotid infusion or i.v. injection, there was uniform distribution of isotope in the same brain regions.


2005 ◽  
Vol 56 (suppl_1) ◽  
pp. ONS-196-ONS-200 ◽  
Author(s):  
Kudret Türeyen ◽  
Raghu Vemuganti ◽  
Kurt A. Sailor ◽  
Robert J. Dempsey

Abstract OBJECTIVE: The use of transgenic and knockout mice has led to a need for a consistent model of mouse transient focal cerebral ischemia. In a great majority of the published mouse middle cerebral artery (MCA) occlusion studies, the methods indicated the type of intraluminal suture used without indicating the actual suture diameter after modification. We attempted to determine the ideal suture diameter to produce consistent occlusion in the MCA of adult male C57BL/6 mice. METHODS: Suture tips were coated to a depth 4 mm with glue, and 6-0 sutures of eight different, precisely measured diameters were produced. The coated 6-0 sutures in different diameters were introduced 10 mm into the internal carotid artery via the external carotid artery of the mice to produce MCA occlusion (n = 40; five animals for each diameter), and the mice (22–24 g) were transaortically perfused with saline. The base of the brain was exposed, and photographs of the vessels were obtained before and after transaortic injection of Evans blue dye to determine the consistency of MCA occlusion for each suture diameter. Cerebral blood flow was measured 10 minutes before occlusion and 20 minutes after reperfusion, and 2,3,5-triphenyltetrazolium chloride staining was performed to demonstrate the ischemic damage in additional animals with 110-μm (n = 5) and 180-μm (n = 8) diameter sutures. RESULTS: Sutures measuring 170 μm and 180 μm in diameter consistently occluded the MCA of C57BL/6 mice. In addition, 2,3,5-triphenyltetrazolium chloride staining demonstrated consistent infarction with180-μm diameter sutures. The infarct volume was 36.3 ± 4.2 mm3. CONCLUSION: Small changes in the diameter of the occlusion suture tip affect consistency in the mouse MCA occlusion model.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Kazutaka Sugimoto ◽  
Andreia Morais ◽  
Homa Sadeghian ◽  
Tao Qin ◽  
David Y. Chung ◽  
...  

Abstract Objectives Spreading depolarizations (SD) likely manifest as aura in migraineurs. Triggers are unknown although vascular events have been implicated. Direct carotid puncture has been reported to trigger migraine with aura. The potent vasoconstrictor endothelin-1 (ET-1), which can be released from the endothelium under pathological conditions, may play a role. Here, we tested whether intracarotid ET-1 infusion triggers SD and whether systemic ET-1 infusion increases the susceptibility to SD. Methods Carotid infusions were performed in mice (C57BL/6, male) through a catheter placed at the carotid bifurcation via the external carotid artery. Intracarotid ET-1 (1.25 nmol/ml) was infused at various rates (2–16 μl/min) with or without heparin in the catheter and compared with vehicle infusion (PBS with 0.01% acetic acid) or sham-operated mice (n = 5). Systemic infusions ET-1 (1 nmol/kg, n = 7) or vehicle (n = 7) infusions were performed in rats (Sprague-Dawley, male) via the tail vein. Electrical SD threshold and KCl-induced SD frequency were measured after the infusion. Results Intracarotid infusion of saline (n = 19), vehicle (n = 7) or ET-1 (n = 12) all triggered SDs at various proportions (21%, 14% and 50%, respectively). These were often associated with severe hypoperfusion prior to SD onset. Heparinizing the infusion catheter completely prevented SD occurrence during the infusions (n = 8), implicating microembolization from carotid thrombi as the trigger. Sham-operated mice never developed SD. Systemic infusion of ET-1 did not affect the electrical SD threshold or KCl-induced SD frequency. Conclusion Intravascular ET-1 does not trigger or increase susceptibility to SD. Microembolization was the likely trigger for migraine auras in patients during carotid puncture.


2019 ◽  
Vol 5 (4) ◽  
pp. 20190014
Author(s):  
Yasith Mathangasinghe ◽  
Radika Udayangani Karunarathne ◽  
Udari Apsara Liyanage

Carotidynia or Transient Perivascular Inflammation of the Carotid Artery (TIPIC) syndrome is a rare cause of atypical neck pain. Exact aetiopathogenesis of this clinical entity is poorly understood. A 43-year-old female presented with progressively increasing right side neck pain of 3 days duration associated with focal tenderness over the right carotid pulse corresponding to the level of upper border of thyroid cartilage. Her inflammatory markers were not elevated. An ultrasound scan revealed increased echogenicity surrounding the distal common carotid artery, obliteration of the perivascular tissue planes with preserved doppler flow pattern. MRI showed soft tissue thickening around the distal common carotid artery, carotid bulb and proximal external carotid artery on right side of the neck corresponding to sonographic findings with gadolinium enhancement. A diagnosis of TIPIC syndrome was made and she was started on celecoxib. Pain completely subsided within 2 weeks. In conclusion, TIPIC syndrome is a rare differential diagnosis of neck pain. It is caused by a transient perivascular inflammation of the carotid artery. A high degree of suspicion is necessary for the diagnosis. Imaging is the gold standard investigation for the diagnosis of TIPIC syndrome. It is a self-limiting pathology and often responds rapidly to nonsteroidal anti-inflammatory drugs.


1992 ◽  
Vol 12 (3) ◽  
pp. 380-389 ◽  
Author(s):  
Eiharu Morikawa ◽  
Myron D. Ginsberg ◽  
W. Dalton Dietrich ◽  
Robert C. Duncan ◽  
Susan Kraydieh ◽  
...  

The purpose of this study was to determine the effect of selective modulation of brain temperature in the experimental settings of permanent and reversible middle cerebral artery (MCA) occlusion in Sprague–Dawley rats. Three models of proximal MCA occlusion were used, in which the effect of brain-temperature modulations could be studied. These included (a) permanent MCA occlusion with an initial 30-min period of hypotension (30 or 36°C × 4 h), (b) permanent MCA occlusion alone (30, 36, or 39°C × 2 h), and (c) 2 h of reversible MCA occlusion (30, 36, or 39°C × 2 h). In the transient MCA occlusion series, intra- and postischemic cortical blood flow was assessed using a laser–Doppler flowmeter placed over the dorsolateral cortex. After a 3-day survival, all rats were perfusion fixed for histopathological analysis and the determination of infarct volume. In animals with permanent MCA occlusion plus hypotension, no significant difference in infarct volume was demonstrated between the 30 and 36°C groups. In rats with permanent MCA occlusion without hypotension, significant differences in infarct volume were again not demonstrable, but an interaction between infarct area and temperature class was shown by repeated-measures analysis, indicating that hypothermia altered the topographic pattern of the cortical infarct. With 2 h of reversible MCA occlusion, there was a statistically significant reduction in infarct volume in the 30°C group compared to 39°C rats. Although intra- and postischemic CBF were not significantly different among the three temperature groups, the cortical infarct volume was positively correlated with postischemic CBF. The postischemic CBF, in turn, was positively correlated to the intraischemic brain temperature and was negatively correlated to CBF during the ischemic period. These findings demonstrate that moderate manipulations of brain temperature have a greater influence on the resulting cortical infarction in the setting of transient focal ischemia than in the context of permanent vascular occlusion.


1997 ◽  
Vol 87 (4) ◽  
pp. 595-601 ◽  
Author(s):  
Ludmila Belayev ◽  
Raul Busto ◽  
Weizhao Zhao ◽  
James A. Clemens ◽  
Myron D. Ginsberg

✓ The authors examined the effect of delayed high-concentration albumin therapy on ischemic injury in a highly reproducible model of middle cerebral artery (MCA) occlusion in rats. Male Sprague—Dawley rats weighing 270 to 320 g were anesthetized with halothane and subjected to 120 minutes of temporary MCA occlusion induced by means of a poly-l-lysine—coated intraluminal nylon suture inserted retrograde via the external carotid artery into the internal carotid artery and MCA. The agent (20% human serum albumin [HSA]) or control solution (sodium chloride 0.9%) was administered intravenously at a dosage of 1% of body weight immediately after suture removal following a 2-hour period of MCA occlusion. The animals' neurological status was evaluated during MCA occlusion (at 60 minutes) and daily for 3 days thereafter. The brains were perfusion-fixed, and infarct volumes and brain edema were determined. The HSA significantly improved the neurological score compared with saline at 24 hours after MCA occlusion. The rats treated with HSA also had significantly reduced total infarct volume (by 34%) and brain edema (by 81%) compared with saline-treated rats. There was a strong correlation between hematocrit level and brain edema (p < 0.01), and between total infarct volume or brain edema and neurological score at 24, 48, and 72 hours postinjury (p < 0.0002). These results strongly support the beneficial effect of delayed albumin therapy in transient focal ischemia and indicate its possible usefulness in treating patients with acute ischemic stroke.


2007 ◽  
Vol 14 (2) ◽  
pp. 208-213 ◽  
Author(s):  
Edward Y. Woo ◽  
Jagajan Karmacharya ◽  
Omaida C. Velazquez ◽  
Jeffrey P. Carpenter ◽  
Christopher L. Skelly ◽  
...  

2019 ◽  
Vol 23 (3) ◽  
pp. 325-332
Author(s):  
Manish Kuchakulla ◽  
Ashish H. Shah ◽  
Valerie Armstrong ◽  
Sarah Jernigan ◽  
Sanjiv Bhatia ◽  
...  

OBJECTIVECarotid body tumors (CBTs), extraadrenal paragangliomas, are extremely rare neoplasms in children that often require multimodal surgical treatment, including preoperative anesthesia workup, embolization, and resection. With only a few cases reported in the pediatric literature, treatment paradigms and surgical morbidity are loosely defined, especially when carotid artery infiltration is noted. Here, the authors report two cases of pediatric CBT and provide the results of a systematic review of the literature.METHODSThe study was divided into two sections. First, the authors conducted a retrospective review of our series of pediatric CBT patients and screened for patients with evidence of a CBT over the last 10 years (2007–2017) at a single tertiary referral pediatric hospital. Second, they conducted a systematic review, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, of all reported cases of pediatric CBTs to determine the characteristics (tumor size, vascularity, symptomatology), treatment paradigms, and complications.RESULTSIn the systematic review (n = 21 patients [includes 19 cases found in the literature and 2 from the authors’ series]), the mean age at diagnosis was 11.8 years. The most common presenting symptoms were palpable neck mass (62%), cranial nerve palsies (33%), cough or dysphagia (14%), and neck pain (19%). Metastasis occurred only in 5% of patients, and 19% of cases were recurrent lesions. Only 10% of patients presented with elevated catecholamines and associated sympathetic involvement. Preoperative embolization was utilized in 24% of patients (external carotid artery in 4 and external carotid artery and vertebral artery in 1). Cranial nerve palsies (cranial nerve VII [n = 1], IX [n = 1], X [n = 4], XI [n = 1], and XII [n = 3]) were the most common cause of surgical morbidity (33% of cases). The patients in the authors’ illustrative cases underwent preoperative embolization and balloon test occlusion followed by resection, and both patients suffered from transient Horner’s syndrome after embolization.CONCLUSIONSSurgical management of CBTs requires an extensive preoperative workup, anesthesia, and multimodal surgical management. Due to a potentially high rate of surgical morbidity and vascularity, balloon test occlusion with embolization may be necessary in select patients prior to resection. Careful thorough preoperative counseling is vital to preparing families for the intensive management of these children.


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