scholarly journals Reduction of infarct volume and apoptosis by grafting of encapsulated basic fibroblast growth factor—secreting cells in a model of middle cerebral artery occlusion in rats

2003 ◽  
Vol 99 (6) ◽  
pp. 1053-1062 ◽  
Author(s):  
Kenjiro Fujiwara ◽  
Isao Date ◽  
Tetsuro Shingo ◽  
Hideyuki Yoshida ◽  
Kazuki Kobayashi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Middle Cerebral Artery ◽  
Fibroblast Growth Factor ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Fibroblast Growth ◽  
Content Type ◽  
And Control ◽  
Cerebral Artery Occlusion ◽  
Fine Print

Object. This study was conducted to evaluate the effects of grafting encapsulated basic fibroblast growth factor (bFGF)—secreting cells in rat brains subjected to ischemic injury. Methods. Two cell lines were used for encapsulated grafting in this experiment, namely, a bFGF-secreting cell line established by genetic manipulation of baby hamster kidney (BHK) cells, and a naive BHK cell line. Forty-seven Sprague—Dawley rats were used in this experiment. The animals were divided into the following three groups: those receiving grafts of encapsulated bFGF-secreting cells (BHK-bFGF group); those with grafts of encapsulated naive BHK cells (naive BHK group); and those with no grafts (control group). The authors implanted encapsulated cells into the right striatum of host rats in the BHK-bFGF and naive BHK groups. Six days after grafting, the host and control animals underwent permanent right middle cerebral artery occlusion (MCAO) with an intraluminal suture procedure. The infarct volume was evaluated using 2,3,5-triphenyltetrazolium chloride staining and computerized image analysis 24 hours after MCAO. Fragmentations of DNA in the host brains were analyzed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling 12 hours after MCAO. The authors found that the infarct volume in the BHK-bFGF group was reduced by approximately 30% compared with that in the naive BHK and control groups. In the ischemic penumbral area, the number of apoptotic cells in the BHK-bFGF group was significantly decreased compared with that in the other groups. Conclusions. The grafting of encapsulated BHK bFGF-secreting cells protected the brain from ischemic injury. Encapsulation and grafting of genetically engineered cells such as bFGF-secreting cells is thus thought to be a useful method for protection against cerebral ischemia.

Posttraumatic bilateral middle cerebral artery occlusion

1975 ◽  
Vol 42 (2) ◽  
pp. 217-221 ◽  
Author(s):  
Skip Jacques ◽  
C. Hunter Shelden ◽  
D. Thomas Rogers ◽  
Anthony C. Trippi
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Content Type ◽  
Pathophysiological Mechanisms ◽  
Cerebral Artery Occlusion ◽  
Fine Print

✓ The authors report a case of bilateral posttraumatic middle cerebral artery occlusion. Previously reported unilateral cases are reviewed and possible pathophysiological mechanisms disscussed.

Indomethacin-mediated improvement following middle cerebral artery occlusion in cats

1985 ◽  
Vol 62 (6) ◽  
pp. 874-881 ◽  
Author(s):  
Robert J. Dempsey ◽  
Mark W. Roy ◽  
Kathleen L. Meyer ◽  
David L. Donaldson
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Artery Occlusion ◽  
Opposite Hemisphere ◽  
Content Type ◽  
Beneficial Effects ◽  
Cerebral Artery Occlusion ◽  
Fine Print

✓ Focal cerebral ischemia initiates multiple detrimental effects in the brain. Chief among these are the regional development of ischemic edema, decreased local perfusion, altered neuronal function, and eventual infarction. To determine if pretreatment with the cyclo-oxygenase inhibitor, indomethacin, would result in improvement in these parameters, adult cats were given indomethacin or control solvent (4 mg/kg intraperitoneally twice daily) and were studied for periods up to 24 hours after right middle cerebral artery occlusion. The interaction of anesthetic agents with indomethacin was also examined in separate groups of experimental animals using pentobarbital and ketamine. In cats allowed to recover from pentobarbital anesthesia, indomethacin reduced gray and white matter edema at 6 and 24 hours after occlusion (p < 0.05). This was noted in densely ischemic areas (indomethacin = 84.3%, control = 87.5%), in “penumbra” regions (indomethacin = 82.5%, control = 85.3%), and in nonischemic zones (indomethacin = 81.5%, control = 82.3%) at 24 hours. Somatosensory evoked potential amplitude and central latency were also improved in the indomethacin group (p < 0.05), as was cerebral perfusion (p < 0.05). In animals anesthetized with continuous ketamine administration, cerebral edema and perfusion as well as evoked potentials were not significantly improved in any region by indomethacin. Regional cerebral blood flow in the group was increased by indomethacin in the nonischemic opposite hemisphere (indomethacin = 64.7 cc/100 gm/min, control = 48.5 cc/100 gm/min, p < 0.05), but not in the penumbra region of the ischemic hemisphere (indomethacin = 15.0 cc/100 gm/min, control = 18.6 cc/100 gm/min, p < 0.05), when measured 4 hours after occlusion. This suggested a steal phenomenon. Beneficial effects of indomethacin were evident in the presence of pentobarbital, but not after ketamine anesthesia. This suggests a synergism dependent on decreased arachidonic acid production from pentobarbitalstabilized membranes coupled with diminished production of cyclic endoperoxides from available arachidonate due to inhibition of cyclo-oxygenase with indomethacin.

Influence of simultaneous pressor and vasodilatory agents on the evolution of infarct growth in experimental acute middle cerebral artery occlusion

2020 ◽  
pp. neurintsurg-2020-016539
Author(s):  
Niloufar Saadat ◽  
Gregory A Christoforidis ◽  
Yong Ik Jeong ◽  
Mira Liu ◽  
Alexey Dimov ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Infarct Volume ◽  
Volume Growth ◽  
Artery Occlusion ◽  
Blood Pressure Elevation ◽  
And Control ◽  
Cerebral Artery Occlusion

BackgroundThis study sought to test the hypothesis that simultaneous central blood pressure elevation and potent vasodilation can mitigate pial collateral-dependent infarct growth in acute ischemic stroke.MethodsTwenty mongrel canines (20–30 kg) underwent permanent middle cerebral artery occlusion (MCAO). Eight subjects received continuous infusion of norepinephrine (0.1–1.5200 µg/kg/min; titrated to a median of 34 mmHg above baseline mean arterial pressure) and hydralazine (20 mg) starting 30 min following MCAO. Pial collateral recruitment was scored prior to treatment and used to predict infarct volume based on a previously reported parameterization. Serial diffusion magnetic resonance imaging (MRI) acquisitions tracked infarct volumes over a 4-hour time frame. Infarct volumes and infarct volume growth between treatment and control groups were compared with each other and to predicted values. Fluid-attenuated inversion recovery (FLAIR) MRI, susceptibility weighted imaging (SWI), and necropsy findings were included in the evaluation.ResultsDifferences between treatment and control group varied by pial collateral recruitment based on indicator-variable regression effects analysis with interaction confirmed by regression model fit. Benefit in treatment group was only in subjects with poor collaterals which had 35.7% less infarct volume growth (P=0.0008; ANOVA) relative to controls. Measured infarct growth was significantly lower than predicted by the model (linear regression partial F-test, slope P<0.001, intercept=0.003). There was no evidence for cerebral hemorrhage or posterior reversible encephalopathy syndrome.ConclusionOur results indicate that a combination of norepinephrine and hydralazine administered in the acute phase of ischemic stroke mitigates infarct evolution in subjects with poor but not good collateral recruitment.

Skull bone regeneration in primates in response to basic fibroblast growth factor

1999 ◽  
Vol 91 (5) ◽  
pp. 851-856 ◽  
Author(s):  
Yasuhiko Tabata ◽  
Keisuke Yamada ◽  
Liu Hong ◽  
Susumu Miyamoto ◽  
Nobuo Hashimoto ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Regeneration ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Fibroblast Growth ◽  
Skull Defect ◽  
Skull Bone ◽  
Content Type ◽  
X Ray ◽  
Fine Print

Object. The feasibility of using a biodegradable hydrogel incorporating basic fibroblast growth factor (bFGF) to induce bone regeneration at the site of a skull defect in monkeys was investigated.Methods. Basic fibroblast growth factor was incorporated into a bioabsorbable hydrogel, which was prepared through glutaraldehyde crosslinking of gelatin. Following treatment of monkey skull defects measuring 6 mm in diameter (six defects/experimental group) with gelatin hydrogel incorporating bFGF, skull bone regeneration was evaluated using soft x-ray studies, dual x-ray absorptometry, and histological examinations.The water content of the hydrogels varied according to the glutaraldehyde concentration in the hydrogel preparation. Gelatin hydrogels incorporating 100 µg of bFGF significantly promoted bone regeneration and the skull defect was completely closed 21 weeks after implantation. This is in marked contrast with the effect of the same dose of bFGF in solution form. Bone mineral density (BMD) measured at the sites of skull defect was enhanced by the bFGF-incorporating hydrogels. The BMD enhancement was more prominent at lower water contents of hydrogel. Empty gelatin hydrogels neither induced nor interfered with skull bone regeneration.Conclusions. The findings of this study indicate that bFGF coupled with bioabsorbable hydrogel is a very promising tool to assist in the regrowth of bone at the site of a skull defect, which clinically has been recognized as almost impossible.

Negative autoregulation of fibroblast growth factor receptor 2 expression characterizing cranial development in cases of Apert (P253R mutation) and Pfeiffer (C278F mutation) syndromes and suggesting a basis for differences in their cranial phenotypes

2001 ◽  
Vol 95 (4) ◽  
pp. 660-673 ◽  
Author(s):  
Jonathan A. Britto ◽  
Rachel L. Moore ◽  
Robert D. Evans ◽  
Richard D. Hayward ◽  
Barry M. Jones
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Apert Syndrome ◽  
Fibroblast Growth ◽  
Content Type ◽  
Pfeiffer Syndrome ◽  
Negative Autoregulation ◽  
Fine Print

Object. Heterogeneous mutations in the fibroblast growth factor receptor 2 gene (FGFR2) cause a range of craniosynostosis syndromes. The specificity of the Apert syndrome—affected cranial phenotype reflects its narrow mutational range: 98% of cases of Apert syndrome result from an Ser252Trp or Pro253Arg mutation in the immunoglobulin-like (Ig)IIIa extracellular subdomain of FGFR2. In contrast, a broad range of mutations throughout the extracellular domain of FGFR2 causes the overlapping cranial phenotypes of Pfeiffer and Crouzon syndromes and related craniofacial dysostoses. Methods. In this paper the expression of FGFR1, the IgIIIa/c and IgIIIa/b isoforms of FGFR2, and FGFR3 is investigated in Apert syndrome (P253R mutation)— and Pfeiffer syndrome (C278F mutation)—affected fetal cranial tissue and is contrasted with healthy human control tissues. Both FGFR1 and FGFR3 are normally expressed in the differentiated osteoblasts of the periosteum and osteoid, in domains overlapped by that of FGFR2, which widely include preosseous cranial mesenchyme. Expression of FGFR2, however, is restricted to domains of advanced osseous differentiation in both Apert syndrome— and Pfeiffer syndrome—affected cranial skeletogenesis in the presence of fibroblast growth factor (FGF)2, but not in the presence of FGF4 or FGF7. Whereas expression of the FGFR2-IgIIIa/b (KGFR) isoform is restricted in normal human cranial osteogenesis, there is preliminary evidence that KGFR is ectopically expressed in Pfeiffer syndrome—affected cranial osteogenesis. Conclusions. Contraction of the FGFR2-IgIIIa/c (BEK) expression domain in cases of Apert syndrome— and Pfeiffer syndrome—affected fetal cranial ossification suggests that the mutant activation of this receptor, by ligand-dependent or ligand-independent means, results in negative autoregulation. This phenomenon, resulting from different mechanisms in the two syndromes, offers a model by which to explain differences in their cranial phenotypes.

Induced seizures as therapy of experimental strokes in dogs

1971 ◽  
Vol 34 (2) ◽  
pp. 178-184 ◽  
Author(s):  
Ronald R. Reed ◽  
Conrad Ciesel ◽  
Guy Owens
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Oxidative Metabolism ◽  
Collateral Circulation ◽  
Seizure Activity ◽  
Artery Occlusion ◽  
Content Type ◽  
Elevated Rate ◽  
Cerebral Artery Occlusion ◽  
Fine Print

✓ Intracerebral pO2, as measured in normal dog brains by a modified mass spectrometer, was found to increase following seizure activity and remain elevated at least 2 hours. These results were found with both drug- and electrically-induced seizures. The pO2 increased to a greater degree in brain tissue rendered ischemic by middle cerebral artery occlusion. A transient reflex hypertension was observed with seizure activity, but hypertension alone failed to produce significant pO2 changes. Since oxidative metabolism has been shown by other investigators to proceed at an elevated rate during seizure activity, the increased pO2 must reflect improved collateral circulation following seizure activity.

Expression of the basic fibroblast growth factor gene in mild and more severe head injury in the rat

1998 ◽  
Vol 89 (2) ◽  
pp. 297-302 ◽  
Author(s):  
Shu-Yuan Yang ◽  
Jian-Zhong Cui
Keyword(s):  
Brain Injury ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Severe Injury ◽  
Fibroblast Growth ◽  
Content Type ◽  
Injury Group ◽  
Fine Print

Object. The goal of this study was to investigate the relationship between basic fibroblast growth factor (bFGF) gene expression and neuropathological changes in the hippocampus after varying degrees of brain injury. Methods. Mild and severe brain injury in rats was produced by using Marmarou's method. There were 25 animals in each brain injury group and 25 additional animals served as controls. Basic fibroblast growth factor gene expression was investigated by means of RNA hybridization, in situ hybridization, immunohistochemical analysis, and histological analysis using hematoxylin and eosin staining. A 3.7-kb bFGF messenger (m)RNA was detected in the rat hippocampus in both control and injured rats. In the mild injury group its expression was increased at 12 hours after injury and peaked on the 3rd day. Neuronal degeneration in the hippocampal CA2 and CA3 sectors was maximum on that day. In the severe injury group, the expression of the bFGF gene was the same as that in the mild injury group at corresponding times, but the number of surviving neurons in the CA2 and CA3 sectors was much lower than in the mild injury group. In situ hybridization showed that the main cells that expressed bFGF mRNA were pyramidal and granulocytic neurons in all three experimental groups. The number of neurons expressing bFGF mRNA in the severe injury group was less than that in the mild injury group, but the intensity of expression was greater. Immunohistochemical staining showed that the number of neurons expressing the bFGF protein was less in the severe injury group than in the mild injury group. Conclusions. It is concluded that after mild injury there is a close relationship between the expression of the bFGF gene and the degree of histological change in the hippocampus; this indicates that as one of the growth factors, bFGF may participate in the protection and repair processes of neurons following brain injury. In severe injury there is a reduced expression of bFGF. The reason for this appears to be that more of the cells that have the potential to express bFGF have died, reducing the ability to express the bFGF gene. Conversely, it is possible that there may be an intrinsic insufficiency of expression of the gene, compatible with the known vulnerability of the hippocampus to many pathological conditions. Consideration should be given to supplying exogenous bFGF to protect the brain, particularly the hippocampus, after injury.

Use of mild intraischemic hypothermia versus mannitol to reduce infarct size after temporary middle cerebral artery occlusion in rats

1995 ◽  
Vol 83 (1) ◽  
pp. 93-98 ◽  
Author(s):  
Hiroshi Karibe ◽  
Gregory J. Zarow ◽  
Philip R. Weinstein
Keyword(s):  
Blood Flow ◽  
Infarct Size ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Content Type ◽  
Infarct Area ◽  
Group A ◽  
Group B ◽  
Cerebral Artery Occlusion ◽  
Fine Print

✓ To determine which of two treatments for reducing ischemic injury after temporal focal ischemia is more effective, the effects of mild (33°C) intraischemic hypothermia were compared with those of mannitol, the most commonly used neuroprotective agent. Four groups of Sprague-Dawley rats underwent 1 hour of endovascular middle cerebral artery occlusion followed by 23 hours of normothermic reperfusion. The four experimental groups were as follows: Group A, saline control; Group B, mannitol (25%, 1 g/kg); Group C, hypothermia; and Group D, hypothermia plus man-nitol. Laser-Doppler estimates of cortical blood flow showed that hypothermia did not affect blood flow during ischemia or reperfusion. Mannitol increased cortical blood flow during ischemia and reperfusion under both normothermic and hypothermic conditions (p < 0.05). Neurological deficit was significantly less severe in treated rats (Group B, p < 0.05; Group C or D, p < 0.01) than in controls (Group A). Infarct volume, measured on semiserial Nissl-stained sections, was significantly smaller in treated rats (p < 0.01) than in controls. Infarct volume was also significantly smaller in rats treated with hypothermia than in those treated with mannitol (Group C vs. Group B, p < 0.05); there was no difference between rats treated with mannitol and those treated with mannitol and hypothermia. All three treatments reduced infarct area in the ischemic penumbra; hypothermia with or without mannitol also reduced infarct area in the ischemic core. These results demonstrate that both mild intraischemic hypothermia and mannitol reduce infarct size and neurological deficit: hypothermia reduces infarct size more effectively than mannitol, and mannitol adds no significant protection to hypothermia, whereas hypothermia adds significant protection beyond that afforded by mannitol after brief focal ischemia followed by reperfusion in rats. The results suggest that mild intraischemic hypothermia alone, or in combination with mannitol, may be useful in avoiding ischemic injury from temporary vessel occlusion during cerebrovascular surgery.

Retargeting of adenoviral vector using basic fibroblast growth factor ligand for malignant glioma gene therapy

2005 ◽  
Vol 103 (6) ◽  
pp. 1058-1066 ◽  
Author(s):  
Weijun Wang ◽  
Nian-Ling Zhu ◽  
Jason Chua ◽  
Steve Swenson ◽  
Fritz K. Costa ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Cell Lines ◽  
Malignant Gliomas ◽  
Glioma Cells ◽  
Transduction Efficiency ◽  
Fibroblast Growth ◽  
Content Type ◽  
Fine Print

Object. Adenovirus vector (AdV)—mediated gene delivery has been recently demonstrated in clinical trials as a novel potential treatment for malignant gliomas. Combined coxsackievirus B and adenovirus receptor (CAR) has been shown to function as an attachment receptor for multiple adenovirus serotypes, whereas the vitronectin integrins (αvβ3 and αvβ5) are involved in AdV internalization. In resected glioma specimens, the authors demonstrated that malignant gliomas have varying levels of CAR, αvβ3, and αvβ5 expression. Methods. A correlation between CAR expression and the transduction efficiency of AdV carrying the green fluorescent protein in various human glioblastoma multiforme (GBM) cell lines and GBM primary cell lines was observed. To increase transgene activity in in vitro glioma cells with low or deficient levels of CAR, the authors used basic fibroblast growth factor (FGF2) as a targeting ligand to redirect adenoviral infection through its cognate receptor, FGF receptor 1 (FGFR1), which was expressed at high levels by all glioma cells. These findings were confirmed by in vivo study data demonstrating enhanced transduction efficiency of FGF2-retargeted AdV in CAR-negative intracranial gliomas compared with AdV alone, without evidence of increased angiogenesis. Conclusions. Altogether, the results demonstrated that AdV-mediated gene transfer using the FGF2/FGFR system is effective in gliomas with low or deficient levels of CAR and suggested that FGF2-retargeting of AdV may be a promising approach in glioma gene therapy.

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