Scar Zone Research Articles

Gliosis and brain remodeling after treatment of stroke in rats with marrow stromal cells

The long-term (4-month) responses to treatment of stroke in the older adult rat, using rat bone marrow stromal cells (MSCs), have not been investigated. Retired breeder rats were subjected to middle cerebral artery occlusion (MCAo) alone, or injected intravenously with 3 x 10(6) MSCs, at 7 days after MCAo. Functional recovery was measured using an adhesive-removal patch test and a modified neurological severity score. Bromodeoxyuridine, a cell proliferation marker, was injected daily for 14 before sacrifice. Animals were sacrificed 4 months after stroke. Double immunostaining was used to identify cell proliferation and cell types for axons, astrocytes, microglia, and oligodendrocytes. MSC treatment induced significant improvement in neurological outcome after MCAo compared with control rats. MSC treatment reduced the thickness of the scar wall (P < 0.05) and reduced the numbers of microglia/macrophages within the scar wall (P < 0.01). Double staining showed increased expression of an axonal marker (GAP-43), among reactive astrocytes in the scar boundary zone and in the subventricular zone in the treated rats. Bromodeoxyuridine in cells preferentially colocalized with markers of astrocytes (GFAP) and oligodendrocytes (RIP) in the ipsilateral hemisphere, and gliogenesis was enhanced in the subventricular zone of the rats treated with MSCs. This is the first report to show that MSCs injected at 7 days after stroke improve long-term neurological outcome in older animals. Brain tissue repair is an ongoing process with reactive gliosis, which persists for at least 4 months after stroke. Reactive astrocytes responding to MSC treatment of ischemia may also promote axonal regeneration during long-term recovery.

Effects of Aesthetic Abdominoplasty on Abdominal Wall Perfusion: A Quantitative Evaluation

Abdominoplasty procedures involve a high risk of early complications, including hematomas, seromas, necrosis, and wound-healing problems. Their rationale is evident from the vascular anatomy of the abdominal wall, as traditional abdominoplasty includes a division of the main perforating vessels. No studies exist to quantitatively assess the consequences of abdominoplasty on the perfusion of the random pattern abdominal flap. To address this issue and quantify the influence of classic abdominoplasty on the perfusion of the abdominal skin, the authors performed a prospective clinical trial including 15 low-risk patients undergoing abdominoplasty for aesthetic purposes. Perfusion of the abdominal flap was measured intraoperatively using the technique of dynamic laser-fluorescence-videoangiography. In the region between the umbilicus and the transverse scar (zone 1), the increment of fluorescence (the slope of the intensity curve during inflow of the indocyanine green) was recorded and compared with the intensity curve of normal tissue that was not involved in surgery (thoracic wall). The results of the intraoperative indocyanine green perfusography showed a significant impairment of the vascular supply of zone 1 in all patients. The mean perfusion index in this region was 17.2 percent (range, 5 to 32 percent) of the perfusion of the surrounding skin that was not involved in surgery. The complication rate was 33 percent (five patients) and included two cases of hematoma and three cases of scar dehiscence with skin and/or fat necrosis. These data indicate that conventional abdominoplasty including extended undermining and division of the superficial and the deep arterial systems causes profound devascularization of the abdominal flap. This might explain the high incidence of complications following this procedure.

Mode of initiation and ablation of ventricular fibrillation storms in patients with ischemic cardiomyopathy

ObjectivesWe report on the initiation of ventricular fibrillation (VF) storm in patients with ischemic cardiomyopathy (ICM) and the results of targeted ablation to treat VF storm. BackgroundMonomorphic premature ventricular contractions (PVCs) have been shown to initiate VF in patients without structural heart disease. MethodsA total of 29 patients with ICM and documented VF initiation were identified. In 21 patients, VF storm was controlled with antiarrhythmic drugs and/or treatment of heart failure. Eight patients with VF (mean 52 ± 25 episodes) refractory to medical management required ablation. All patients underwent three-dimensional electroanatomical mapping using CARTO (Biosense-Webster Inc., Diamond Bar, California), and PVCs were mapped when present. Scarred areas were identified using voltage mapping. ResultsMonomorphic PVCs initiated VF in all 29 identified patients. Five of eight patients requiring ablation had frequent PVCs that allowed PVC mapping. The earliest activation site was consistently located in the scar border zone. The PVCs were always preceded by a Purkinje-like potential (PLP). Ablation was successfully performed at these sites. In three patients, infrequent PVCs prevented mapping, but PLPs were recorded around the scar border. Ablation targeting these potentials along the scar border was successfully performed. During follow-up (10 ± 6 months), one patient had a single VF episode and another developed sustained, monomorphic ventricular tachycardia. There was no recurrence of VF storm. ConclusionsVentricular fibrillation in ICM is triggered by monomorphic PVCs originating from the scar border zone with preceding PLPs; targeting these PVCs may prevent VF recurrence. In the absence of PVCs, both substrate mapping and ablation appear to be equally effective.

Vascular endothelial growth factor transgene expression in cell-transplanted hearts

ObjectiveWe evaluated the effect of transplanted cell type, time, and region of the heart on transgene expression to determine the potential of combined gene and cell delivery for myocardial repair. MethodsLewis rats underwent myocardial cryoinjury 3 weeks before transplantation with heart cells (a mixed culture of cardiomyocytes, smooth muscle cells, endothelial cells and fibroblasts, n = 13), vascular endothelial growth factor–transfected heart cells (n = 13), skeletal myoblasts (n = 13), vascular endothelial growth factor–transfected skeletal myoblasts (n = 13), or medium (control, n = 12). Vascular endothelial growth factor expression in the scar, border zone, and normal myocardium was evaluated at 3 days and at 1, 2, and 4 weeks by means of quantitative polymerase chain reaction. Transplanted cells and vascular endothelial growth factor protein were identified immunohistologically on myocardial sections. ResultsVascular endothelial growth factor levels were very low in control scars but increased transiently after medium injection. Transplantation with heart cells and skeletal myoblasts significantly increased vascular endothelial growth factor expression in the scar and border zone. Transplantation of vascular endothelial growth factor–transfected heart cells and vascular endothelial growth factor–transfected skeletal myoblasts further augmented vascular endothelial growth factor expression, resulting in 4- to 5-fold greater expression of vascular endothelial growth factor in the scar at 1 week. Peak vascular endothelial growth factor expression was greater and earlier in vascular endothelial growth factor–transfected heart cells than in vascular endothelial growth factor–transfected skeletal myoblasts. Vascular endothelial growth factor was primarily expressed by the transplanted cells. Some of the transplanted heart cells and vascular endothelial growth factor–transfected heart cells were identified in the endothelial layer of blood vessels in the scar. ConclusionsTransplantation of heart cells and skeletal myoblasts induces vascular endothelial growth factor expression in myocardial scars and is greatly augmented by prior transfection with a vascular endothelial growth factor transgene. Vascular endothelial growth factor expression is limited to the scar and border zone for 4 weeks. Both heart cells and skeletal myoblasts may be excellent delivery vehicles for cell-based myocardial gene therapy.

Extended Upper Blepharoplasty for Lateral Hooding of the Upper Eyelid Using a Scalpel-Shaped Excision: A 13-Year Experience

Excess skin of the upper lids is often accompanied by lateral overlap of skin with crow's feet because of the absence of fixation to the tarsal plate, giving the eye a sad, heavy look that often disturbs the lateral visual field. The accepted crescent-shaped blepharoplasty is somewhat convex, which is widest at the center of the lid with or without a lateral extension. However, in patients who have normal brow position or minimal eyebrow ptosis and whose main concern is the excess upper eyelid skin and lateral hooding, such a crescent excision may not suffice. A scalpel-shaped excision that is widest laterally and that tapers to a point medially will extirpate the maximal skin where it is most needed and overcome the skin excess in the lateral aspect of the upper lid. Between 1990 and 2002, 301 white patients (275 women and 26 men) between the ages of 33 and 79 years were operated on using the extended scalpel-shaped upper blepharoplasty technique. The follow-up period was more than 1 year. The lower margin of the incision is along the supratarsal crease, about 10 mm above the ciliary line. It begins medially about 1 cm above and lateral to the medial canthus. Above the lateral canthus, the skin marking is gently curved upward and outward, often within a natural skin crease or crow's feet to reach a little below and slightly beyond the lateral extremity of the eyebrow. The upper border of the incision joins the two extremities of the skin outline in a gentle convex curve. The general outline of the incision takes on the shape of a number 20 scalpel blade in which the maximal width is located laterally. Following excision of the excess skin and removal of protuberant fat pads if needed, suturing is executed from lateral to medial. The final suture line is in the form of an oblique flattened lazy S. Following the removal of the stitches on the fifth postoperative day, no wound dehiscence was noticed at the lateral scar zone. In the older individuals, due to the lax skin, the scar becomes scarcely noticeable with time and often falls within a pre-existent crow's feet crease. Elimination of some of the crow's feet was also demonstrated. In patients with visual field impairment, significant functional and visual improvement was achieved. Most patients mentioned a pleasing postoperative open "Oriental" look of the eyes. The extended scalpel-shaped upper blepharoplasty adequately deals with the hooding of the skin laterally. This technique overcomes the excess of skin in both vertical and horizontal directions, since in suturing the lateral part of the skin defect in an oblique plane, slack skin is taken up transversely, and the technique provides some indirect upward support to the lateral eyebrow. In the absence of crow's feet in the younger person, this technique is not recommended because the lateral part of this suture line is visible, especially if the scar widens.

Characterization of cardiac myocyte and tissue beta-adrenergic signal transduction in rats with heart failure.

The cellular basis of alterations in beta-adrenergic signal transduction in rats with chronic heart failure (CHF) remains unclear. The aim of the present study was to examine this signal transduction system in isolated ventricular cardiomyocytes of rats with CHF. We focused on changes in the levels of stimulatory (Gs) and inhibitory G-proteins (Gi). CHF was induced in male Wistar rats by coronary artery ligation (CAL). Hemodynamic and biochemical parameters were measured 8 weeks after CAL. Alterations in contractile function and Ca(2+) transients via beta-adrenergic receptor signaling of cardiomyocytes isolated from rats with CHF were characterized by simultaneous measurements of cell shortening and fura-2 fluorescence intensity. Coronary artery-ligated rats showed symptoms of CHF, such as decreased contractile function, increased left ventricular volume, decreased chamber stiffness, and about 40% infarct formation of the left ventricle, by 8 weeks after surgery. The contractile function and Ca(2+) dynamics of cardiomyocytes from the rats with CHF remained normal under basal conditions. Only cardiac cell length was increased. The responses of peak shortening, fura-2 fluorescence ratio amplitude, and cAMP content to beta-adrenoceptor stimulation were reduced in cardiomyocytes of the rats with CHF, whereas direct stimulation of adenylate cyclase did not affect the response of these variables. Cardiomyocyte Gsalpha protein was decreased, whereas no changes in Gialpha proteins were seen in these cells. Increases in tissue Gsalpha and Gialpha proteins in the scar zone were detected. The results on tissue levels of collagen and G-proteins in the viable left ventricle appeared to depend on the presence of nonmyocytes. The results suggest that impaired contractile function of cardiomyocytes is unlikely to account for global LV contractile dysfunction, and that down-regulation of beta-adrenoceptors occurs in cardiomyocytes per se. The difference in changes of G-protein between the cardiomyocyte and myocardial tissue suggests an appreciable contribution of nonmyocytes to myocardial G-protein levels.

Myofibroblast-like cells and wound contraction in leech wound healing

This research aims to characterize the wound contraction process in the leech Hirudo medicinalis since much evidence indicates that the cells that form the pseudoblastema act in wound contraction as well as in phagocytosis and in regenerative processes. In H. medicinalis the pseudoblastema is formed by a single type of connective cell, the vasocentral cells. Electron microscopy and actin labeling with phalloidin are used to follow the behavior of vasocentral cells and actin bundles present in their cytoplasm through the healing process. During the formation and evolution of the pseudoblastema, vasocentral cells undergo several changes. When the pseudoblastema consolidates, cell junctions are formed, and the actin bundles are seen to converge with them. At this moment, the cells, and therefore the actin bundles, are lying parallel to the surface. At the time that wound contraction occurs, the cells and also the actin bundles orientate perpendicular to the wound surface, and the pseudoblastema retracts. During this stage, actin bundles become enlarged, cell-to-cell adhering junctions become more conspicuous, and the intercellular space is filled with a filamentous material. The thickening and reorganization of the actin bundles are correlated with the development of wound contraction. These findings give support to the hypothesis that tension within the wound is generated by the formation of intracellular stress fibers and transmitted by the interaction of the stress fibers with the extracellular matrix or with neighboring cells through extracellular space, analogous to the role played by myofibroblasts in vertebrate wound healing. Despite some differences, the similarity between vasocentral cells and myofibroblasts is remarkable and may reflect a requirement for contractile elements in the scar zone directed towards producing the wound contraction phenomenon. © 1996 Wiley-Liss, Inc.

Biomaterial supports for colonic wall defect healing: An experimental study in the rat

New artificial biomaterials were tested for support of gastro-intestinal tract wound healing in the rat. Double layered collagenic matrices were prepared with purified collagens extracted from human placental tissues. Two types of patches were tested, the first constituted from a collagen type I + III layer covered by collagen IV in a liquid phase (patch I + III/IV) and the second from a collagen IV layer covered by liquid collagen IV (patch IV/IV). The matrices were applied with fibrin sealant to the edges of a 1 cm diameter colonie wall defect in the rat. Healing evolution was determined by macroscopic, microscopic and immunostaining studies. The reconstitution of the three colonic wall layers was achieved within 45 days without retraction or inflammatory reaction, while the biomaterial was resorbed. Human collagen I and III antibodies failed to stain extracellular matrix. This failure may be a consequence of outdated antibodies or more likely epitope alteration during extraction and preparation of the collagens. A human collagen type IV antibody staining of the scar zone showed the basement membranes of newly developed vessels within 10 days, and newly formed colonic mucosa within 20 days. The collagen reconstituted matrix was able to assist healing of normal digestive tract defects as shown by the labelling of the new synthesized extracellular matrix by collagen type IV antibody. These findings support the use of collagen biomaterial in gastro-intestinal anastomosis. This new surgical approach allowing healing of colonic wall defects could reduce occurrence of anastomotic leakage in human.

SeaMARC II study of a giant submarine slump on the northern Chile continental slope

Abstract A giant submarine slump, encompassing a 91‐km by 26‐km block, occurring on the continental slope offshore Iquique, Chile, was identified during a SeaMARC II survey. Utilizing SeaMARC II side‐scan imagery, bathymetry, and seismic reflection data, five morphostructural zones of the slump were identified: the fissured zone, scar zone, tensional depression, central block, and front zone. The fissured zone was developed on the crown of the slump; the scar zone is characterized by scars with the crescent‐shaped slip surfaces and throws ranging from 200 m to 50 m. The tensional depression zone is marked by an area voided by mass slumping, while the central block morphology was formed by uplift. The front zone is comprised of both compressional and tensional subzones. The compressional subzone is characterized by a relative topographic low, on the middle slope, whereas the extensional subzone is characterized by a convex pattern of alternated ridges and hollows, which may represent the debris of the slump on the lower slope. The formation of the slump was strongly influenced by the subduction of the Nazca plate beneath the Chile continental margin, which resulted in the subsidence of the continental slope with a resultant increase in the slope gradient and pore‐water pressure in the sedimentary layers. Slump formation was further facilitated by the development of a complex fault system associated with the subduction and by the triggering effect of earthquakes in the area.

Non-invasive quantification of exercise-induced changes in regional left ventricular function in normals and patients with one vessel coronary artery disease using radionuclide ventriculography.

To quantitate changes in regional left ventricular function induced by ischemia or scar, rest and exercise equilibrium radionuclide studies of 26 patients with one vessel coronary artery disease and 12 normal individuals were analysed with a new method for regional ejection fraction determination. A computer algorithm provided observer-independent segmental analysis from a centre of gravity of the left ventricular activity at end-diastole (left anterior oblique projection). Special segments were assigned for anteroseptal, inferoapical and posterolateral areas corresponding to the three main coronary arteries. Reproducibility using an unchanged camera positioning was excellent even for 2 min acquisition studies (r=0.93) and still good after repositioning (r=0.80 to 0.87). In normal areas, regional ejection fraction increased or showed no change during exercise. In contrast, it decreased significantly in regions supplied by stenosed coronary arteries (ischemia) and remained depressed in scar zones. The method proved to be valid for regional changes induced by left anterior descending and left circumflex coronary obstructions, but less for right coronary artery lesions. Global ejection fraction reflected a sum of all regional changes implying that regional analysis should be more sensitive in detecting coronary artery disease.

Offshore-seismic surveying technique

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Development of perifocal edema in experimental epilepsy induced by cobalt-gelatin.

Two blood-borne tracers, Evans-blue albumin (EBA) and colloidal-iron (Ferrlecit) were applied to visualize the development of perifocal edema in experimental epilepsy induced by cobalt-gelatin (Co-gelatin). This model is known to produce central necrosis with gliomesenchymal scar and peripheral transitory zone in the brain cortex. Characteristic red fluorescence of EBA was detected diffusely in the necrotic area surrounding the Co-gelatin implant and EBA labelled individual neurons reflecting cell membrane injury in the transitory zone. The colloidal iron tracer was localized mainly in the gliomesenchymal scar. It is proposed that neurons with altered membrane permeability to EBA in the transitory zone may play a role in the genesis of epileptic spike activity. The marked labelling of the gliomesenchymal scar by colloidal-iron indicates furthermore that this newly vascularized tissue with leaky capillaries may be a source of perifocal edema.

The mechanics of erosion

It is anticipated that an increase in rainfall will have significant impacts on the geomorphology of permafrost landscapes. Field observations, remote sensing and historical climate data were used to investigate the drivers, processes and feedbacks that perpetuate the growth of large retrogressive thaw slumps. These “mega slumps” (5–40 ha) are now common in formerly glaciated, fluvially incised, ice-cored terrain of the Peel Plateau, NW Canada. Individual thaw slumps can persist for decades and their enlargement due to ground ice thaw can displace up to 106 m3 of materials from slopes to valley bottoms reconfiguring slope morphology and drainage networks. Analysis of Landsat images (1985–2011) indicate that the number and size of active slumps and debris tongue deposits has increased significantly with the recent intensification of rainfall. The analyses of high resolution climatic and photographic time-series for summers 2010 and 2012 shows strong linkages amongst temperature, precipitation and the downslope sediment flux from active slumps. Ground ice thaw supplies meltwater and sediments to the slump scar zone and drives diurnal pulses of surficial flow. Coherence in the timing of down valley debris tongue deposition and fine-scaled observations of sediment flux indicate that heavy rainfall stimulates major mass flow events. Evacuation of sediments from the slump scar zone can help to maintain a headwall of exposed ground ice, perpetuating slump growth and leading to larger disturbances. The development of debris tongue deposits divert streams and increase thermoerosion to initiate adjacent slumps. We conclude that higher rainfall can intensify thaw slump activity and rapidly alter the slope-sediment cascade in regions of ice-cored glaciogenic deposits.

Two Uncommon Cases of Complete Atrioventricular Block with Edems-Stokes Syndrome

Complete atrioventricular (atrioventricular) block is very rare - according to various domestic and foreign authors, from 0.2 to 1%. A complete atrioventricular block is most often based on sclerotic lesions of the heart muscle with the involvement of a specific cardiac conduction system in the process. Among other causes of complete atrioventricular block, traumatic injuries of the interventricular septum with involvement of a specific conducting system of the heart into the wound or scar zone are known (V. T. Uverskaya and others).