Glial cell extracellular matrix: boundaries for axon growth in development and regeneration

The validation of a simple quantitative clinical test of personal neglect is described in this study of 17 right brain damaged CVA patients with extrapersonal neglect, 14 without unilateral extrapersonal neglect, 13 left brain damaged CVA patients and 17 age-matched controls. The test had a high reliability and clearly differentiated neglect patients from all other groups. Furthermore the test identified a much higher incidence of personal neglect among extrapersonal neglect patients (59%) than has previously been found. Moreover this study confirms earlier findings by showing a double dissociation between personal and extrapersonal neglect. Seven patients with extrapersonal neglect showed no personal neglect while five patients showing no extrapersonal neglect did show personal neglect on this test.     

Glial tumor cell proliferation and immune response in the brain

Absence of the maxillary lateral incisor creates an aesthetic problem which can be managed in various ways. The condition requires careful treatment planning and a consideration of the options and outcomes following either space closure or prosthetic replacement. Recent developments in restorative dentistry have warranted a re-evaluation of the approach to this clinical situation. Factors relating both to the patient and to the teeth, including the presenting malocclusion and the effect on the occlusion, are considered. This review considers the possible options: no treatment; orthodontic space closure with canine modification; space maintenance and replacement of the missing tooth with denture, bridge (adhesive and conventional), or implant.     

Lateralized response to cortical injury in the rat: Interhemispheric interaction.

Two experiments, with 92 male Sprague-Dawley rats, examined the role of interhemispheric interaction in the production of spontaneous hyperactivity following right but not left frontal cortical suction lesions. Bilateral lesions, either simultaneous or left followed 1 wk later by right, led to spontaneous hyperactivity and bilateral depletions of cortical norepinephrine concentrations. Ss given corpus callosum sectioning as neonates and frontal cortical suction lesions as adults developed spontaneous hyperactivity only when the right hemisphere was injured. Data suggest that lateralized spontaneous hyperactivity as elicited by small suction lesions of the right hemisphere does not depend on interhemispheric release or interaction and that at least the cortical mechanism is in the right hemispere itself. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cerebral hemodynamic response to CO2 after severe head injury: clinical and prognostic implications

PURPOSE: To evaluate the efficacy and safety of transcatheter oily chemoembolization therapy (TOCE) via the inferior phrenic artery (IPA) in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Fifty patients with HCC underwent a total of 82 procedures of TOCE of the IPA, as well as of the hepatic artery. In 16 patients, additional extrahepatic collaterals were depicted and were also embolized in 10 patients. TOCE was performed with an emulsion of iodized oil and doxorubicin hydrochloride, and gelatin sponge particle embolization was added in 32 patients. RESULTS: Initial response showed complete or partial remission of the tumor in 31 patients. The cumulative survival rates after combined TOCE of the hepatic artery, IPA, and other extrahepatic arteries were 89% (6 months), 78% (1 year), 46% (2 year), and 30% (3 year), when calculated from the time of IPA chemoembolization. Liver abscess and empyema developed in one case of combined IPA and multiple intercostal artery chemoembolization. There were no serious complications after IPA chemoembolization alone. CONCLUSION: TOCE of the IPA has a potential therapeutic role as a safe adjunct to TOCE of the hepatic artery in the management of HCC supplied by the IPA.     

Sertoli cell-specific expression of rat androgen-binding protein in transgenic mice: effects on somatic cell lineages

The Sertoli cells of many species produce an androgen binding protein (ABP) which carries testicular androgens to the epididymis and is thought to play a role in sperm maturation. In the present report we analyzed the morphological modifications present in Leydig, Sertoli, and peritubular cells of the testis of young adult male mice transgenic for ABP gene, which overproduce ABP in testis. By in situ hybridization we demonstrated that ABP is specifically produced by Sertoli cells. Using light and electron microscopy, we detected scattered alterations of the seminiferous tubule cells which include cell degeneration and vacuolization. Leydig and Sertoli cells present morphological signs of hyperfunctioning compensatory mechanisms which include increased amounts of lipid droplets probably due to the existence of a stimulated steroid synthesis that in turn could be a consequence of the decreased unbound testosterone and/or a direct paracrine effect of ABP. Peritubular cells also present numerous signs of hyperstimulation.     

Physiology of primary saccular afferents of goldfish: implications for Mauthner cell response

Mauthner cells receive neurally coded information from the otolith organs in fishes, and it is most likely that initiation and directional characteristics of the C-start response depend on this input. In the goldfish, saccular afferents are sensitive to sound pressure (< -30 dB re: 1 dyne cm-2) in the most sensitive frequency range (200 to 800 Hz). This input arises from volume fluctuations of the swimbladder in response to the sound pressure waveform and is thus nondirectional. Primary afferents of the saccule, lagena, and utricle of the goldfish also respond with great sensitivity to acoustic particle motion (< 1 nanometer between 100 and 200 Hz). This input arises from the acceleration of the fish in a sound field and is inherently directional. Saccular afferents can be divided into two groups based on their tuning: one group is tuned at about 250 Hz, and the other tuned between 400 Hz and 1 kHz. All otolithic primary afferents phaselock to sinusoids throughout the frequency range of hearing (up to about 2 kHz). Based on physiological and behavioral studies on Mauthner cells, it appears that highly correlated binaural input to the M-cell, from the sacculi responding to sound pressure, may be required for a decision to respond but that the direction of the response is extracted from small deviations from a perfect interaural correlation arising from the directional response of otolith organs to acoustic particle motion.     

Lipolytic response of rat adipocytes to epinephrine: effect of age and cell size

Isolated fat cells from 3, 12 and 28 month old rats were compared intheir lipolytic response to various doses of L-epinephrine. With increasing age a progressive decline in the response occurred when comparing rats with unmatched mean adipocyte diameters. However, this apparently age-related decrease was no longer evident if the diameters were matched since the 28 month old animals had a lipolytic response less than the 3 month old rats but greater than the 12 month olds. Body weight differences between these ages may account for these observations. The biphasic dose response curve to hormone stimulation in the 3 and 12 month olds was monophasic at 28 months. Within each age group the initial lag in glycerol release decreased and the lipolytic response increased as mean cell size increased. The rate of hormone stimulated glycerol release varied inversely with incubations of 3,700 to 25,000 cells/ml and aging had no effect on this parameter. DNA content per fat cell remained constant with age.     

The biosynthesis of glycosaminoglycans in normal rat liver and in response to experimental hepatic injury

The synthesis of glycosaminoglycans in slices from normal and acutely injured rat liver was studied. The rates of incorporation of [14C]-glucosamine into specific types of glycosaminoglycans varied markedly; nearly 90% was incorporated into a fraction containing predominantly heparan sulfate and far less if any heparin; about 9.5% was incorporated into chondroitin 4-and 6-sulfate, and only 0.2% of the radioactivity was found in hyaluronic acid. The rate of synthesis of a fraction having several of the characteristics of keratan sulfate comprised only 0.3% of the synthesis of total glycosaminoglycans. No [14C]hexosamine was incorporated into dermatan sulfate. Following acute hepatic injury, the synthesis of glycosaminoglycans was stimulated by 80 to 100%, and the proportions of various types changed. If calculated on the basis of the specific activity of the precursors of glycosaminoglycans, which was found to be strongly reduced in injured liver, the maximum enhancement of total glycosaminoglycan synthesis was 6.6-fold 5 days after onset of liver injury.     

Glial cell interactions with tenascin-C: adhesion and repulsion to different tenascin-C domains is cell type related

The multimodular glycoprotein tenascin-C is transiently expressed, predominantly by glial cells, during the development of the central and peripheral nervous systems. This extracellular matrix glycoprotein is involved in the control of cell adhesion, neuron migration and neurite outgrowth. Distinct functional properties for neuronal cell types have been attributed to separate tenascin-C domains using antibody perturbation studies and in vitro experiments on tenascin-C fragments. In order to study potential roles of tenascin-C for glial cell biology, a library of recombinant tenascin-C domains was used in a bioassay in vitro. Embryonic day 14 astrocytes, various astroglial-derived cell lines (C6, A7 and Neu7) and oligodendroglial-derived cell types (Oli-neu and G26-20) were examined in an adhesion assay and compared to the neuroblastoma cell line N2A. A binding site for most cell types, except for A7 and N2A, could be assigned to the first three fibronectin type III domains. Repulsive properties could be mapped to three different sites the epidermal growth factor-like repeats, fibronectin type III repeats 4 and 5 and to the alternatively spliced region of the molecule. The responses to these repulsive sites varied according to the cell type. These data are consistent with the interpretation that different cell types express distinct sets of tenascin-C receptors which might regulate cellular responses via distinct second messenger pathways.     

Adipose tissue cell size and lipolysis in the rat: response to exercise intensity and food restriction

This experiment was designed to determine if the adaptive increase in adipose tissue epinephrine-stimulated lipolysis (ESL) observed in exercise trained rats is related to decreased adipocyte size or a direct response to exercise. Two levels of treadmill exercise and three levels of food restriction were imposed on male rats over a 12 week experimental period to create a distribution of adipose tissue cell sizes. Epinephrine-stimulated lipolysis was subsequently measured in the isolated adipocytes from rats trained at two different exercise levels and in untrained rats fed either ad libitum or 16%, 27%, or 35% dietary restriction. Energy restriction was effective in reducing body weight and to some extent epididymal fat pad weight; however, adipocyte size and number were not significantly affected. Exercise in both groups of trained rats was effective in reducing adipocyte size; however, cell size did not differ between training groups. The group receiving the greatest amount of daily exercise had significantly greater ESL indicating that the adaptive increase in lipolytic potential seen in adipose tissue of exercise trained rats is a true metabolic adaptation not secondary to reduced cell size.     

The response of fish blood cells, particularly thrombocytes, to decompression

Trans-chest electrical ventricular defibrillation was attempted in eight adult patients using a 400 watt-second truncated exponential decay waveform defibrillator. All attempts occurred in the immediate post-operative period after heart surgery. Five of the eight subjects were defibrillated (63% success). This success rate is similar to that of 300 watt-second damped sinusoidal waveform defibrillators.     

Glial response to neuronal activity: GFAP-mRNA and protein levels are transiently increased in the hippocampus after seizures

We have recently demonstrated that electrically induced seizures lead to dramatic increases in mRNA for GFAP in areas in which seizures occur. The present study evaluates the time course of the changes in the GFAP-mRNA levels after seizures and the relationship between these changes and GFAP protein levels to understand the role of neuronal activity in regulating glial gene expression. GFA protein and mRNA levels were measured in hippocampi from rats in which seizures were induced by: (1) 50-Hz stimulus trains delivered 12 times over the course of 1 day via indwelling electrodes implanted chronically in the CA3 region of the hippocampus; and (2) intraperitoneal injections of pentylenetetrazol. In the case of the electrically induced seizures, we also compared the glial response in animals that had never experienced a seizure with the response in animals that previously had been kindled but had not experienced a seizure for 30 days. Electrically induced seizures led to rapid transient increases in GFAP-mRNA levels in the hippocampus ipsi- and contralateral to the stimulation. GFAP-mRNA increased about five-fold 1 day after the end of seizure activity and returned to near-control levels by 4 days. There were no detectable increases in GFA protein at 1 day but by 2 days GFA protein levels had increased about two-fold. GFA protein levels remained elevated until 4 days poststimulation and then began to decrease. The responses were similar when seizures were induced in kindled animals, except that the GFAP protein levels remained elevated for somewhat longer.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mitochondrial function as a determinant of recovery or death in cell response to injury

Many pathological conditions can be the cause or the consequence of mitochondrial dysfunction. For instance anoxia, which is initiated by a critical reduction of oxygen availability for mitochondrial oxidations, is followed by a wide variety of mitochondrial alterations. A crucial role in the evolution of cell injury is to be attributed to the direction of operation of the F0F1 ATPase, which may turn mitochondria into the major consumers of cellular ATP in the futile attempt to restore the proton electrochemical gradient. On the other hand, functional mitochondria can paradoxically accelerate or exacerbate cell damage. This concept is particularly relevant for the ischemic myocardium. Indeed, inhibition of the respiratory chain or addition of uncouplers of oxidative phosphorylation can both limit the extent of enzyme release in the intact heart and prevent the onset of irreversible morphological changes in isolated myocytes. From studies on different tissues in a variety of pathological conditions a general consensus emerges on the role of intracellular Ca2+ overload as a pivotal link between cellular alterations and mitochondrial dysfunction. Oxidative phosphorylation is reduced by a massive mitochondrial uptake of Ca2+, resulting in a vicious cycle whereby the reduced ATP availability is followed by a failure of the mechanisms which extrude Ca2+ from the sarcoplasm. In addition, the rise in [Ca2+]i could promote opening of the cyclosporin-sensitive mitochondrial permeability transition pore, leading to a sudden deltapsi(m) dissipation. Here, we review the changes in intracellular and intramitochondrial ionic homeostasis occurring during ischemia and reperfusion. In particular, we evaluate the potential contribution of the permeability transition pore to cellular damage and discuss the mechanisms which can determine the cellular fate from a mitochondrial point of view.     

Cystic renal cell carcinoma: pathological features, survival and implications for treatment

Some epidemiological data point to an association between infection from Helicobacter pylori (Hp) and gastric cancer, although several unresolved issues still cast doubts on the real weight of this association. These issues are as follows: the male-to-female ratio of gastric cancer ranges from 4:1 to 1.5:1 in all studies, whereas the prevalence of Hp infection is the same in both sexes; the prevalence of Hp infection is as high as 90% in several developing countries where the frequency of gastric cancer is very low; the acquisition of the infection at a young age, considered very important with regard to the risk for cancer, varies from 4.2% to 83% in several countries in which the mortality for stomach cancer is approximately 10 in 100,000; and the incidence of cancer in patients with a duodenal ulcer is half that of the general population, but Hp infects up to 100% of these patients. In the sequence of events that leads to gastric cancer, Hp appears to play a role only in the very initial steps, as a causative agent of chronic inflammation. The further events that cause gastric atrophy, intestinal metaplasia, dysplasia, and cancer are multifactorial, involving environmental agents and the host response. It is therefore inappropriate to consider Hp a direct carcinogen for humans. This also applies to specific strains of the bacterium such as the cagA gene. In fact, Hp infection is widespread in humans, and only a small minority will ever be affected by peptic ulcer and cancer.     

Vesicular transport: implications for cell polarity

In polarized cells intracellular sorting of plasma membrane proteins occurs to a large extent at the trans-Golgi network, giving rise to vesicles destined for distinct plasma membrane domains. This review discusses the several pathways, both direct and indirect, which lead to protein incorporation into the correct cell surface, as well as the mechanisms involved. Proteins contain signals which direct their incorporation into the distinct vesicles destined for plasma membrane microdomains. Specific coat proteins are involved in vesicle assembly and are likely to play a role in the generation of discrete vesicle populations. Molecules involved in vesicle docking and fusion may also add specificity to the targeting process.     

The pupil response of a teleost fish, Porichthys notatus: description and comparison to other species

The pupil response of Porichthys notatus to different intensities of illumination is described and compared to that of P. myriaster, Cephaloscyllium ventroisum, and a human. While the fully dark adapted pupil is round, at the highest light intensities it consists of only two small, almost independent, apertures with a total area 4.9% of that observed in the fully dilated animal. The response is at least partially consensual and occurs, albeit at a much reduced rate, in isolated eyes. P. notatus also displays retinomotor movements comparable to those seen in most teleosts, suggesting that, contrary to most previous assumptions, pupillary responses and retinomotor migrations are not mutually exclusive.     

The ability of human Schwann cell grafts to promote regeneration in the transected nude rat spinal cord

Advances in the purification and expansion of Schwann cells (SCs) from adult human peripheral nerve, together with biomaterials development, have made the construction of unique grafts with defined properties possible. We have utilized PAN/PVC guidance channels to form solid human SC grafts which can be transplanted either with or without the channel. We studied the ability of grafts placed with and without channels to support regeneration and to influence functional recovery; characteristics of the graft and host/graft interface were also compared. The T9-T10 spinal cord of nude rats was resected and a graft was placed across the gap; methylprednisolone was delivered acutely to decrease secondary injury. Channels minimized the immigration of connective tissue into grafts but contributed to some necrotic tissue loss, especially in the distal spinal cord. Grafts without channels contained more myelinated axons (x = 2129 +/- 785) vs (x = 1442 +/- 514) and were larger in cross-sectional area ( x = 1.53 +/- 0.24 mm2) vs (x = 0.95 +/- 0.86 mm2). The interfaces formed between the host spinal cord and the grafts placed without channels were highly interdigitated and resembled CNS-PNS transition zones; chondroitin sulfate proteoglycans was deposited there. Whereas several neuronal populations including propriospinal, sensory, motoneuronal, and brainstem neurons regenerated into human SC grafts, only propriospinal and sensory neurons were observed to reenter the host spinal cord. Using combinations of anterograde and retrograde tracers, we observed regeneration of propriospinal neurons up to 2.6 mm beyond grafts. We estimate that 1% of the fibers that enter grafts reenter the host spinal cord by 45 days after grafting. Following retrograde tracing from the distal spinal cord, more labeled neurons were unexpectedly found in the region of the dextran amine anterograde tracer injection site where a marked inflammatory reaction had occurred. Animals with bridging grafts obtained modestly higher scores during open field [(x = 8.2 +/- 0.35) vs (x = 6.8 +/- 0.42), P = 0.02] and inclined plane testing (x = 38.6 +/- 0. 542) vs (x = 36.3 +/- 0.53), P = 0.006] than animals with similar grafts in distally capped channels. In summary, this study showed that in the nude rat given methylprednisolone in combination with human SC grafts, some regenerative growth occurred beyond the graft and a modest improvement in function was observed.     

Neural injury repair: hope for the future as barriers to effective CNS regeneration become clearer

In this review the author outlines the early history of clinical and scientific research upon the inability of the CNS in man to successfully regenerate following injury. As we proceed into the 21st Century we have gained a far greater understanding of the molecular biology, pathology and other factors that lead to the adult CNS being non-supportive and indeed actively inhibitory to axonal regrowth. On the basis of these recent advances in knowledge, the author outlines possible therapeutic approaches that may enable more effective CNS regeneration to be accomplished in the future.