Congenic removal of a QTL for blood pressure attenuates infarct size produced by middle cerebral artery occlusion in hypertensive rats

2007 ◽  
Vol 30 (1) ◽  
pp. 69-73 ◽  
Author(s):  
Hiroshi Yao ◽  
Zong-Hu Cui ◽  
Junichi Masuda ◽  
Toru Nabika
Keyword(s):  
Blood Pressure ◽  
Young Adult ◽  
Infarct Size ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Infarct Volume ◽  
Chromosome 1 ◽  
Hypertensive Rats ◽  
Arterial Blood ◽  
Mca Occlusion

A genome-wide screen found a blood pressure quantitative trait locus (QTL) on rat chromosome 1 in stroke-prone spontaneously hypertensive rats of a Japanese colony (SHRSP/Izm). In the present study, we investigated the effects of congenic removal of this QTL from SHRSP/Izm on infarct size produced by middle cerebral artery (MCA) occlusion. To establish the congenic strain (SHRSPwch1.0), the blood pressure QTL was introgressed from Wistar-Kyoto (WKY)/Izm to SHRSP/Izm by repeated backcrossing. Male SHRSP/Izm [10–12 wk old (young adult) n = 8, 5 mo old (adult) n = 17] and SHRSPwch1.0 (young adult n = 7, adult n = 15) were randomly assigned to distal MCA occlusion. Resting mean arterial blood pressure (MABP) was 212 ± 23 mmHg in adult SHRSPwch1.0, which was significantly lower than 241 ± 22 mmHg in SHRSP/Izm. Infarct volume in the congenic rats was significantly decreased compared with that in SHRSP/Izm (66.4 ± 21.5 mm3 vs. 103.4 ± 24.8 mm3). Cerebral blood flow (CBF), determined at collaterally-perfused cortex with laser-Doppler flowmetry after MCA occlusion, was significantly greater in adult SHRSPwch1.0 compared with CBF in adult SHRSP/Izm. In young adult rats, there were no significant differences in MABP or in infarct volume between SHRSPwch1.0 and SHRSP/Izm. The congenic removal of a blood pressure QTL lowered blood pressure and caused a substantial reduction in infarct volume (−36%) with increased collateral CBF after MCA occlusion in the congenic rat. We demonstrated for the first time that the congenic strategy is useful to investigate the effects of genetic hypertension on focal ischemia or stroke.

scholarly journals ARL 17477, a Potent and Selective Neuronal NOS Inhibitor Decreases Infarct Volume after Transient Middle Cerebral Artery Occlusion in Rats

1996 ◽  
Vol 16 (4) ◽  
pp. 599-604 ◽  
Author(s):  
Zheng G. Zhang ◽  
David Reif ◽  
James Macdonald ◽  
Wen Xue Tang ◽  
Dietgard K. Kamp ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Cell Damage ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Arterial Blood ◽  
Mca Occlusion ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Cerebral Artery Occlusion

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.

scholarly journals Larger Anastomoses in Angiotensinogen-Knockout Mice Attenuate Early Metabolic Disturbances after Middle Cerebral Artery Occlusion

1999 ◽  
Vol 19 (10) ◽  
pp. 1092-1098 ◽  
Author(s):  
Keiichiro Maeda ◽  
Ryuji Hata ◽  
Michael Bader ◽  
Thomas Walther ◽  
Konstantin-Alexander Hossmann
Keyword(s):  
Blood Pressure ◽  
Middle Cerebral Artery ◽  
Arterial Blood Pressure ◽  
Cerebral Artery ◽  
Mean Arterial Blood Pressure ◽  
Knockout Mice ◽  
Therapeutic Window ◽  
Wild Type ◽  
Arterial Blood ◽  
Mca Occlusion

Abnormalities in the homeostasis of the renin-angiotensin system have been implicated in the pathogenesis of vascular disorders, including stroke. The authors investigated whether angiotensinogen (AGN) knockout mice exhibit differences in brain susceptibility to focal ischemia, and whether such differences can be related to special features of the collateral circulation. Wild-type and AGN-knockout mice were submitted to permanent suture occlusion of the middle cerebral artery (MCA). The collateral vascular system was visualized by systemic latex infusion, and the ischemic lesions were identified by cresyl-violet staining. The core and penumbra of the evolving infarct were differentiated by bioluminescence and autoradiographic imaging of A TP and protein biosynthesis, respectively. In wild-type mice, mean arterial blood pressure was 95.0 ± 8.6 mm Hg, and the diameter of fully relaxed anastomotic vessels between the peripheral branches of the anterior and middle cerebral arteries 26.6 ± 4.0 μm In AGN knockouts, mean arterial blood pressure was significantly lower, 71.5 ± 8.5 mm Hg ( P <,01), and the anastomotic vessels were significantly larger, 29.4 ± 4.6 μm ( P < .01). One hour after MCA occlusion, AGN-knockout mice exhibited a smaller ischemic core (defined as the region of ATP depletion) but a larger penumbra (the area of disturbed protein synthesis with preserved ATP). At 24 hours after MCA occlusion, this difference disappeared, and histologically visible lesions were of similar size in both strains. The observations show that in AGN-knockout mice the more efficient collateral blood supply delays ischemic injury despite the lower blood pressure. Pharmacologic suppression of angiotensin formation may prolong the therapeutic window for treatment of infarcts.

Association of Infarct Volume Before Hemicraniectomy and Outcome After Malignant Infarction

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000011987
Author(s):  
Dominik Lehrieder ◽  
Katharina Layer ◽  
Hans-Peter Müller ◽  
Viktoria Rücker ◽  
Jan Kassubek ◽  
...  
Keyword(s):  
Infarct Size ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Randomized Trials ◽  
Infarct Volume ◽  
Unfavorable Outcome ◽  
Inclusion Criteria ◽  
Younger Patients ◽  
Malignant Infarction ◽  
The Impact

ObjectiveTo determine the impact of infarct volume before hemicraniectomy in malignant middle cerebral artery infarction (MMI) as an independent predictor for patient selection and outcome prediction, we retrospectively analyzed data of 140 patients from a prospective multi-center study.MethodsPatients from the DESTINY-Registry that underwent hemicraniectomy after ischemic infarction of >50% of the middle cerebral artery territory were included. Functional outcome according to the modified Rankin Scale (mRS) was assessed at 12 months. Unfavorable outcome was defined as mRS 4-6. Infarct size was quantified semi-automatically from computed tomography or magnetic resonance imaging before hemicraniectomy. Subgroup analyses in patients fulfilling inclusion criteria of randomized trials in younger patients (age≤60y) were predefined.ResultsAmong 140 patients with complete datasets (34% female, mean (SD) age 54 (11) years), 105 (75%) had an unfavorable outcome (mRS > 3). Mean (SD) infarct volume was 238 (63) ml. Multivariable logistic regression identified age (OR 1.08 per 1 year increase; 95%-CI 1.02-1.13; p=0.004), infarct size (OR 1.27 per 10ml increase; 95%-CI 1.12-1.44; p<0.001) and NIHSS (OR 1.10; 95%-CI 1.01-1.20; p=0.030) before hemicraniectomy as independent predictors for unfavorable outcome. Findings were reproduced in patients fulfilling inclusion criteria of randomized trials in younger patients. Infarct volume thresholds for prediction of unfavorable outcome with high specificity (94% in overall cohort and 92% in younger patients) were more than 258 ml before hemicraniectomy.ConclusionOutcome in MMI strongly depends on age and infarct size before hemicraniectomy. Standardized volumetry may be helpful in the process of decision making concerning hemicraniectomy.

scholarly journals Tumor necrosis factor-α inhibition attenuates middle cerebral artery remodeling but increases cerebral ischemic damage in hypertensive rats

2014 ◽  
Vol 307 (5) ◽  
pp. H658-H669 ◽  
Author(s):  
Paulo W. Pires ◽  
Saavia S. Girgla ◽  
Guillermo Moreno ◽  
Jonathon L. McClain ◽  
Anne M. Dorrance
Keyword(s):  
Cerebral Ischemia ◽  
Tumor Necrosis Factor ◽  
Infarct Size ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Tumor Necrosis ◽  
Myogenic Tone ◽  
Hypertensive Rats ◽  
Tnf Α ◽  
Necrosis Factor

Hypertension causes vascular inflammation evidenced by an increase in perivascular macrophages and proinflammatory cytokines in the arterial wall. Perivascular macrophage depletion reduced tumor necrosis factor (TNF)-α expression in cerebral arteries of hypertensive rats and attenuated inward remodeling, suggesting that TNF-α might play a role in the remodeling process. We hypothesized that TNF-α inhibition would improve middle cerebral artery (MCA) structure and reduce damage after cerebral ischemia in hypertensive rats. Six-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) were treated with the TNF-α inhibitor etanercept (ETN; 1.25 mg·kg−1·day−1 ip daily) or PBS (equivolume) for 6 wk. The myogenic tone generation, postischemic dilation, and passive structure of MCAs were assessed by pressure myography. Cerebral ischemia was induced by MCA occlusion (MCAO). Myogenic tone was unchanged, but MCAs from SHRSP + ETN had larger passive lumen diameter and reduced wall thickness and wall-to-lumen ratio. Cerebral infarct size was increased in SHRSP + ETN after transient MCAO, despite an improvement in dilation of nonischemic MCA. The increase in infarct size was linked to a reduction in the number of microglia in the infarct core and upregulation of markers of classical macrophage/microglia polarization. There was no difference in infarct size after permanent MCAO or when untreated SHRSP subjected to transient MCAO were given ETN at reperfusion. Our data suggests that TNF-α inhibition attenuates hypertensive MCA remodeling but exacerbates cerebral damage following ischemia/reperfusion injury likely due to inhibition of the innate immune response of the brain.

Acute Middle Cerebral Artery Occlusion: Experience with Volume Expansion Therapy

Neurosurgery ◽  
1986 ◽  
Vol 18 (4) ◽  
pp. 397-401 ◽  
Author(s):  
Bruce I. Tranmer ◽  
Cordell E. Gross ◽  
Ted S. Keller ◽  
Glenn W. Kindt
Keyword(s):  
Cardiac Output ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Volume Expansion ◽  
Artery Occlusion ◽  
Neurological Deficits ◽  
Life Styles ◽  
Arterial Blood ◽  
Mca Occlusion ◽  
The Mean

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 &lt; 0.05). The mean hematocrit decreased 19% from 46 + 3% to 37 + 4% (P &lt; 0.01). The mean arterial blood pressure remained stable, and the pulmonary artery wedge pressure was maintained at &lt; 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 &lt;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.

A high-potassium diet reduces infarct size and improves vascular structure in hypertensive rats

2007 ◽  
Vol 292 (1) ◽  
pp. R415-R422 ◽  
Author(s):  
Anne M. Dorrance ◽  
David M. Pollock ◽  
Olga P. Romanko ◽  
David W. Stepp
Keyword(s):  
Blood Pressure ◽  
Ischemic Stroke ◽  
Growth Factor ◽  
Infarct Size ◽  
Cerebral Artery ◽  
Vascular Structure ◽  
Hypertensive Rats ◽  
High Potassium ◽  
Wky Rats ◽  
Potassium Supplementation

High-potassium diets can improve vascular function, yet the effects of potassium supplementation on ischemic stroke have not been studied. We hypothesized that dietary potassium supplementation would reduce ischemic cerebral infarct size by reversing cerebral artery hypertrophy. Six-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) were fed diets containing 0.79% potassium (LK) or 2.11% potassium (HK) for 6 wk; Wistar-Kyoto (WKY) rats were fed the LK diet. The HK diet did not reduce blood pressure, as measured by telemetry, in the SHRSP. Cerebral ischemia was induced by middle cerebral artery (MCA) occlusion. The resultant infarct was smaller in the HK-SHRSP than in the LK-SHRSP: 55.1 ± 6.3 vs. 71.4 ± 2.4% of the hemisphere infarcted ( P < 0.05). Infarcts were smaller in WKY rats (33.5 ± 4.8%) than in LK-SHRSP or HK-SHRSP. The vessel wall of MCAs from LK-SHRSP was hypertrophied compared with WKY rats; this was reversed in HK-SHRSP. RT-PCR analysis of the cerebral vessels showed that expression of platelet-derived growth factor receptors-α and -β, epidermal growth factor receptor, and collagen I and III was increased in the vessels from LK-SHRSP compared with WKY rats and reduced in HK-SHRSP. These results suggest that potassium supplementation provides neuroprotection in a model of ischemic stroke independent of blood pressure and possibly through changes in vascular structure.

Proximal occlusion of the middle cerebral artery in C57Black6 mice: relationship of patency of the posterior communicating artery, infarct evolution, and animal survival

2004 ◽  
Vol 100 (1) ◽  
pp. 97-105 ◽  
Author(s):  
Kazuhide Furuya ◽  
Nobutaka Kawahara ◽  
Kensuke Kawai ◽  
Tomikatsu Toyoda ◽  
Keiichiro Maeda ◽  
...  
Keyword(s):  
Survival Rate ◽  
Infarct Size ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Posterior Communicating Artery ◽  
Neurological Deficits ◽  
Content Type ◽  
Fine Print

Object. The intraluminal suture model for focal cerebral ischemia is increasingly used, but not without problems. It causes hypothalamic injury, subarachnoid hemorrhage, and inadvertent premature reperfusion. The patency of the posterior communicating artery (PCoA) potentially affects the size of the infarct. In addition, survival at 1 week is unstable. The authors operated on C57Black6 mice to produce proximal middle cerebral artery occlusion (MCAO) so that drawbacks with the suture model could be circumvented. Methods. The MCA segment just proximal to the olfactory branch was occluded either permanently or temporarily. After 1 hour of MCAO the infarct volume was significantly smaller than that found after 2 hours or in instances of permanent MCAO. The differences were assessed at 24 hours and 7 days after surgery (p < 0.05 and p < 0.001, respectively). The patency of the PCoA, as visualized using carbon black solution, did not correlate with the infarct size. Neurologically, the 1- and 2-hour MCAO groups displayed significantly less severe deficits than the permanent MCAO group on Days 1, 4, and 7 (p < 0.005 and p < 0.01, respectively). Although the infarct size, neurological deficits, and body weight loss were more severe in the permanent MCAO group, the survival rate at Day 7 was 80%. Conclusions. This model provides not only a robust infarct size (which is not affected by the patency of the PCoA), but also a better survival rate.

scholarly journals Photothrombotic Occlusion of Rat Middle Cerebral Artery: Histopathological and Hemodynamic Sequelae of Acute Recanalization

1988 ◽  
Vol 8 (3) ◽  
pp. 357-366 ◽  
Author(s):  
Hitoshi Nakayama ◽  
W. Dalton Dietrich ◽  
Brant D. Watson ◽  
Raul Busto ◽  
Myron D. Ginsberg
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Cortical Neurons ◽  
Cell Damage ◽  
Thrombus Formation ◽  
Infarct Volume ◽  
Brain Regions ◽  
Mca Occlusion ◽  
Temporary Occlusion ◽  
Mixed Pattern

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.

Neuroprotective effects of erythropoietin pretreatment in a rodent model of transient middle cerebral artery occlusion

2014 ◽  
Vol 121 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Bernardo Oliveira Ratilal ◽  
Mariana Moreira Coutinho Arroja ◽  
Joao Pedro Fidalgo Rocha ◽  
Adelaide Maria Afonso Fernandes ◽  
Andreia Pereira Barateiro ◽  
...  
Keyword(s):  
Treatment Group ◽  
Middle Cerebral Artery ◽  
Brain Edema ◽  
Cerebral Artery ◽  
Plasma Levels ◽  
Infarct Volume ◽  
Neuron Specific Enolase ◽  
Artery Occlusion ◽  
Mca Occlusion ◽  
Cerebral Artery Occlusion

Object There is an unmet clinical need to develop neuroprotective agents for neurosurgical and endovascular procedures that require transient cerebral artery occlusion. The aim in this study was to explore the effects of a single dose of recombinant human erythropoietin (rhEPO) before middle cerebral artery (MCA) occlusion in a focal cerebral ischemia/reperfusion model. Methods Twenty-eight adult male Wistar rats were subjected to right MCA occlusion via the intraluminal thread technique for 60 minutes under continuous cortical perfusion monitoring by laser Doppler flowmetry. Rats were divided into 2 groups: control and treatment. In the treated group, rhEPO (1000 IU/kg intravenously) was administered 10 minutes before the onset of the MCA ischemia. At 24-hour reperfusion, animals were examined for neurological deficits, blood samples were collected, and animals were killed. The following parameters were evaluated: brain infarct volume, ipsilateral hemispheric edema, neuron-specific enolase plasma levels, parenchyma histological features (H & E staining), Fluoro-Jade–positive neurons, p-Akt and total Akt expression by Western blot analysis, and p-Akt–positive nuclei by immunohistochemical investigation. Results Infarct volume and Fluoro-Jade staining of degenerating neurons in the infarct area did not vary between groups. The severity of neurological deficit (p < 0.001), amount of brain edema (78% reduction in treatment group, p < 0.001), and neuron-specific enolase plasma levels (p < 0.001) were reduced in the treatment group. Perivascular edema was histologically less marked in the treatment group. No variations in the expression or localization of p-Akt were seen. Conclusions Administration of rhEPO before the onset of 60-minute transient MCA ischemia protected the brain from this insult. It is unlikely that rhEPO pretreatment leads to direct neuronal antiapoptotic effects, as supported by the lack of Akt activation, and its benefits are most probably related to an indirect effect on brain edema as a consequence of blood-brain barrier preservation. Although research on EPO derivatives is increasing, rhEPO acts through distinct neuroprotective pathways and its clinical safety profile is well known. Clinically available rhEPO is a potential therapy for prevention of neuronal injury induced by transitory artery occlusion during neurovascular procedures.

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