Isoflurane Provides Long-term Protection against Focal Cerebral Ischemia in the Rat

2007 ◽  
Vol 106 (1) ◽  
pp. 92-99 ◽  
Author(s):  
Hiroaki Sakai ◽  
Huaxin Sheng ◽  
Robert B. Yates ◽  
Kazuyoshi Ishida ◽  
Robert D. Pearlstein ◽  
...  
Keyword(s):  
Infarct Size ◽  
Focal Cerebral Ischemia ◽  
Artery Occlusion ◽  
Carotid Artery Occlusion ◽  
Experimental Models ◽  
K Channel ◽  
Definition Of ◽  
Common Carotid Artery Occlusion ◽  
Cerebral Artery Occlusion

Background Long-term neuroprotection by isoflurane has been questioned. The authors examined factors in experimental models potentially critical to definition of enduring isoflurane neuroprotection. Methods Rats were prepared for temporary middle cerebral artery occlusion (MCAO). Pericranial normothermia was maintained. Neurologic deficits (range, 0-48; 0=no deficit) and cerebral infarct volumes were measured. In experiment 1, rats underwent 50 or 80 min MCAO while awake or anesthetized with 1.8% isoflurane. Blood pressure was controlled with phenylephrine. Outcome was evaluated 2 weeks later. In experiment 2, rats underwent 50 min MCAO while awake or anesthetized with isoflurane, with outcome evaluated 8 weeks later. In experiment 3, rats underwent 50 min MCAO while awake or anesthetized with isoflurane and 2 weeks recovery. Effects of phenylephrine and the mitochondrial adenosine triphosphate-sensitive K channel antagonist 5-hydroxydecanoate were studied. In experiment 4, isoflurane-anesthetized rats underwent 50 min MCAO with permanent or temporary common carotid artery occlusion, with outcome evaluated 2 weeks later. Results In experiment 1, isoflurane reduced neurologic deficit (median+/-interquartile range; awake vs. isoflurane: 11+/-12 vs. 8+/-6 for 80 min and 13+/-4 vs. 3+/-9 for 50 min; P=0.0006) and infarct size (160+/-97 vs. 84+/-62 mm for 80 min and 169+/-78 vs. 68+/-61 mm for 50 min; P<0.0001). In experiment 2, isoflurane protection persisted at 8 weeks after ischemia. In experiment 3, there was no effect of phenylephrine or 5-hydroxydecanoate. In experiment 4, permanent common carotid ligation increased infarct size threefold versus temporary occlusion. Conclusions Isoflurane repeatedly improved long-term neurologic and histologic outcome from focal ischemia independent of ischemia duration, perfusion pressure, or pretreatment with 5-hydroxydecanoate.

scholarly journals In vivo evidence for long-term vascular remodeling resulting from chronic cerebral hypoperfusion in mice

2016 ◽  
Vol 37 (2) ◽  
pp. 726-739 ◽  
Author(s):  
Tom Struys ◽  
Kristof Govaerts ◽  
Wouter Oosterlinck ◽  
Cindy Casteels ◽  
Annelies Bronckaers ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Carotid Artery ◽  
Common Carotid Artery ◽  
Artery Occlusion ◽  
Carotid Artery Occlusion ◽  
Emission Tomography ◽  
Resonance Imaging ◽  
Positron Emission ◽  
Common Carotid Artery Occlusion

We have characterized both acute and long-term vascular and metabolic effects of unilateral common carotid artery occlusion in mice by in vivo magnetic resonance imaging and positron emission tomography. This common carotid artery occlusion model induces chronic cerebral hypoperfusion and is therefore relevant to both preclinical stroke studies, where it serves as a control condition for a commonly used mouse model of ischemic stroke, and neurodegeneration, as chronic hypoperfusion is causative to cognitive decline. By using perfusion magnetic resonance imaging, we demonstrate that under isoflurane anesthesia, cerebral perfusion levels recover gradually over one month. This recovery is paralleled by an increase in lumen diameter and altered tortuosity of the contralateral internal carotid artery at one year post-ligation as derived from magnetic resonance angiography data. Under urethane/α-chloralose anesthesia, no acute perfusion differences are observed, but the vascular response capacity to hypercapnia is found to be compromised. These hemispheric perfusion alterations are confirmed by water [15O]-H2O positron emission tomography. Glucose metabolism ([18F]-FDG positron emission tomography) or white matter organization (diffusion-weighted magnetic resonance imaging) did not show any significant alterations. In conclusion, permanent unilateral common carotid artery occlusion results in acute and long-term vascular remodeling, which may have immediate consequences for animal models of stroke but also vascular dementia.

scholarly journals Intraventricular Brain-Derived Neurotrophic Factor Reduces Infarct Size after Focal Cerebral Ischemia in Rats

1997 ◽  
Vol 17 (5) ◽  
pp. 500-506 ◽  
Author(s):  
Wolf-R. Schäbitz ◽  
Stefan Schwab ◽  
Matthias Spranger ◽  
Werner Hacke
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Size ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Neurotrophic Factor ◽  
Cortical Neurons ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Cerebral Artery Occlusion

Brain-derived neurotrophic factor (BDNF), acting through the high-affinity receptor tyrosine kinase (TrkB), is widely distributed throughout the central nervous system and displays in vitro trophic effects on a wide range of neuronal cells, including hippocampal, cerebellar, and cortical neurons. In vivo, BDNF rescues motorneurons, hippocampal, and substantia nigral dopaminergic cells from traumatic and toxic brain injury. After transient middle cerebral artery occlusion (MCAO), upregulation of BDNF-mRNA in cortical neurons suggests that BDNF potentially plays a neuroprotective role in focal cerebral ischemia. In the current study, BDNF (2.1 μg/d) in vehicle or vehicle alone (controls) was delivered intraventricularly for 8 days, beginning 24 hours before permanent middle cerebral artery occlusion by intraluminal suture in Wistar rats (n = 13 per group). There were no differences in physiological variables recorded during surgery for the two groups. Neurological deficit (0 to 4 scale), which was assessed on a daily basis, improved in BDNF-treated animals compared with controls ( P < 0.05; analysis of variance and Scheffe's test). There were no significant differences in weight in BDNF-treated animals and controls during the experiment. After elective killing on day 7 after MCAO, brains underwent 2,3,5-triphenyltetrazolium chloride staining for calculation of the infarct volume and for histology (hematoxylin and eosin and glial fibrillary acid protein). The mean total infarct volume was 83.1 ± 27.1 mm3 in BDNF-treated animals and 139.2 ± 56.4 mm3 in controls (mean ± SD; P < 0.01, unpaired, two-tailed t-test). The cortical infarct volume was 10.8 ± 7.1 mm3 in BDNF-treated animals and 37.9 ± 19.8 mm3 in controls (mean ± SD; P < 0.05; unpaired, two-tailed t-test), whereas ischemic lesion volume in caudoputaminal infarction was not significantly different. These results show that pretreatment with intraventricular BDNF reduces infarct size after focal cerebral ischemia in rats and support the hypothesis of a neuroprotective role for BDNF in stoke.

scholarly journals Relevance of Interstitial Glutamate to Selective Vulnerability in Focal Cerebral Ischemia

1994 ◽  
Vol 14 (2) ◽  
pp. 343-347 ◽  
Author(s):  
Hitoshi Osuga ◽  
Antoine M. Hakim
Keyword(s):  
Focal Cerebral Ischemia ◽  
Selective Vulnerability ◽  
Artery Occlusion ◽  
Carotid Artery Occlusion ◽  
Cerebral Microdialysis ◽  
Additional Time ◽  
Index Of Exposure ◽  
The Difference ◽  
Common Carotid Artery Occlusion

Glutamate concentrations in striatum and cortex were measured by means of in vivo cerebral microdialysis before and for 4 h after middle cerebral and ipsilateral common carotid artery occlusion in rats. The peak glutamate concentration reached 7.28 ± 3.60 μ M in dialysate from striatum and 5.64 ± 2.24 μ M in that from cortex. An index of exposure of each region to glutamate was calculated by integrating glutamate concentrations after occlusion. During ischemia the striatum was exposed to statistically higher cumulative concentrations of glutamate than the cortex (p < 0.01). The difference in vulnerability between striatum and cortex may arise from the additional time needed for the cortex to be exposed to cumulative threshold levels of glutamate.

Down-Regulation of Nogo-A and PirB in Ischemic Cortex with Remote Ischemic Preconditioning in Mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jiao Y ◽  
◽  
Wang J ◽  
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Neuronal Damage ◽  
Focal Cerebral Ischemia ◽  
Artery Occlusion ◽  
Remote Ischemic Preconditioning ◽  
Tetrazolium Chloride ◽  
Hematoxylin And Eosin ◽  
Cerebral Artery Occlusion

Objectives: The present study aims to investigate the effect of Limb Remote Ischemic Preconditioning (LRIP) on the expression of Nogo-A and PirB in the cortex of mice with focal cerebral ischemia, and related pathways involving in axonal regeneration and neurological function recovery after cerebral ischemia. Methods: Adult male C57/BL6 mice were divided into sham-operated (sham), transient Middle Cerebral Artery Occlusion (MCAO), LRIP and anti- PirBAb treatment group. Samples were collected 48h after cerebral ischemia. The histopathologic changes were assessed by 1,3,5-Triphenyl-2H-Tetrazolium Chloride (TTC), and Hematoxylin and Eosin (HE) staining and TUNEL method. The expression of Nogo-A and PirB were determined by immunofluorescence, RT-PCR and Western blot respectively. Results: TTC staining showed that LRIP treatment reduced the infarct size of mice and anti-PirBAb treatment further decline the infarct size, which was accompanied with the decline of neurological deficit score and reduction of neuronal damage. LRIP treatment also reduced the TUNEL positive cells induced by MCAO and anti-PirBAb treatment further strengthened the effect of LRIP. Except sham group, the expressions of Nogo-A and PirB in other three groups all increased with varying degrees, among which MCAO group was the highest, LRIP group was the second and the anti-PirBAb group was the lowest. The expressions of growth associated protein 43 (GAP43) showed opposite tendency. Conclusions: LRIP plays beneficial influence on cerebral ischemia. LRIP and PirB inhibition combination has a better protective effect on nervous system after cerebral ischemia in mice.

scholarly journals TNF-α Pretreatment Induces Protective Effects against Focal Cerebral Ischemia in Mice

1997 ◽  
Vol 17 (5) ◽  
pp. 483-490 ◽  
Author(s):  
Hiroshi Nawashiro ◽  
Kaoru Tasaki ◽  
Christl A. Ruetzler ◽  
John M. Hallenbeck
Keyword(s):  
Infarct Size ◽  
Focal Cerebral Ischemia ◽  
Immunohistochemical Analysis ◽  
Artery Occlusion ◽  
Dependent Manner ◽  
Protective Effects ◽  
Ischemic Brain ◽  
Ischemic Episode ◽  
Factor Α ◽  
Cerebral Artery Occlusion

Cytokines are recognized to play an important role in acute stroke. Tumor necrosis factor- α (TNF) is one of the pro-inflammatory cytokines and is expressed in ischemic brain. We hypothesized that TNF might play a role in the regulation of tolerance to ischemia when administered prior to the ischemic episode. We studied the effects of pretreatment of TNF administered intravenously, intraperitoneally, or intracisternally in mice that were subjected to middle cerebral artery occlusion (MCAO) 48 h later. MCAO was performed in BALB/C mice by direct cauterization of distal MCA, which resulted in pure cortical infarction. A significant reduction in infarct size was noted in mice pretreated by TNF at the dose of 0.5 μg/mouse (p < 0.01) intracisternally. At the doses used in this study, administration of TNF by intravenous or intraperitoneal routes was not effective. Immunohistochemical analysis of brains subjected to 24 h of MCAO revealed a significant decrease in CD11b immunoreactivity after TNF pretreatment compared with control MCAO. Preconditioning with TNF affects infarct size in a time- and dose-dependent manner. TNF induces significant protection against ischemic brain injury and is likely to be involved in the signaling pathways that regulate ischemic tolerance.

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