RESUMEN
BACKGROUND AND OBJECTIVE: Postranslational modification of proteins can lead to the production of autoantibodies and loss of immune tolerance. This process has been hypothesised to be a critical factor in the pathogenesis of rheumatoid arthritis. The objective of this study was to demonstrate that inflamed human gingival tissue provides an extrasynovial source of malondialdehyde-acetaldehyde adducts, citrullinated and carbamylated proteins all of which are considered to be linked to the development of rheumatoid arthritis. Identification of such modified proteins in inflamed gingiva may explain, in part, how inflammation of the periodontal tissues may influence the development of rheumatoid arthritis. MATERIAL AND METHODS: Gingival biopsies of healthy, mild and moderate periodontitis were triple stained with antibodies against malondialdehyde-acetaldehyde adducts, citrullinated and carbamylated proteins. RESULTS: Assessment of healthy gingival tissue revealed negligible staining for carbamylated, malondialdehyde-acetaldehyde (MAA), or citrullinated proteins. Mild periodontitis was positive for all three modifications. Furthermore, there was an increase in staining intensity for carbamylated, citrullinated and MAA-modified proteins in moderate periodontitis. Negative staining results were observed for the isotype controls. CONCLUSION: This study provides evidence for the presence of citrullinated, carbamylated and MAA adduct modified proteins in inflamed periodontal tissues. The potential for these proteins to play a role in autoimmunity in a multi-system inflammatory syndromic disease model now needs to be determined.
Asunto(s)
Acetaldehído/metabolismo , Carbamatos/metabolismo , Citrulinación/inmunología , Encía/metabolismo , Malondialdehído/metabolismo , Acetaldehído/inmunología , Anciano , Anticuerpos/metabolismo , Carbamatos/inmunología , Estudios de Casos y Controles , Humanos , Malondialdehído/inmunología , Persona de Mediana Edad , Periodontitis/metabolismoRESUMEN
Clostridium perfringens type D causes enterotoxemia in sheep and goats. The disease is mediated by epsilon toxin (ETX), which affects the cerebrovascular endothelium, increasing vascular permeability and leading to cerebral edema. In the present study, we compared the distribution and severity of the cerebrovascular changes induced in lambs by C. perfringens type D strain CN1020, its isogenic etx null mutant, and the ETX-producing complemented mutant. We also applied histochemical and immunohistochemical markers to further characterize the brain lesions induced by ETX. Both ETX-producing strains induced extensive cerebrovascular damage that did not differ significantly between each other in nature, neuroanatomic distribution, or severity. By contrast, lambs inoculated with the etx mutant or sterile, nontoxic culture medium did not develop detectable brain lesions, confirming that the neuropathologic effects observed in these infections are dependent on ETX production. Lambs treated with the wild-type and complemented strains showed perivascular and mural vascular edema, as well as serum albumin extravasation, particularly severe in the cerebral white matter, midbrain, medulla oblongata, and cerebellum. Brains of animals inoculated with the ETX-producing strains showed decreased expression of glial fibrillary acidic protein and increased expression of aquaporin-4 in the end-feet processes of the astrocytes around blood vessels. Early axonal injury was demonstrated with anti-amyloid precursor protein immunohistochemistry. Perivascular accumulation of macrophages/microglia with intracytoplasmic albumin globules was also observed in these animals. This study demonstrates that ETX is responsible for the major cerebrovascular changes in C. perfringens type D-induced disease.
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Encéfalo/patología , Clostridium perfringens/patogenicidad , Enterotoxemia/patología , Enfermedades de las Ovejas/patología , Animales , Acuaporina 4/análisis , Encéfalo/irrigación sanguínea , Química Encefálica , Clostridium perfringens/genética , Enterotoxemia/microbiología , Proteína Ácida Fibrilar de la Glía/análisis , Ovinos , Enfermedades de las Ovejas/microbiologíaRESUMEN
STUDY DESIGN: An immunohistological assessment of substance P (SP), its NK1 receptor and claudin-5 in human spinal cord injury (SCI) tissue. OBJECTIVE: To determine whether SP and NK1 receptor immunoreactivity are altered following human traumatic SCI. SETTING: Australia. SUMMARY OF BACKGROUND DATA: SP has been implicated in the development of neurogenic inflammation and subsequent edema development following both traumatic brain injury and ischemic stroke. In these conditions, inhibition of its NK1 receptor has been shown to be neuroprotective as reflected in a reduction of edema and improved functional outcome. However, the role of SP following human SCI has not yet been assessed. METHODS: Archived human SCI tissue was grouped according to survival times: control (no injury; n=5); immediate (death within an hour of the incident; n=6); 2-5 h (n=3); 3 days (n=5); 1 week (n=3); and 3-4 weeks (n=6). Sections were assessed for SP, its NK1 receptor and claudin-5 using immunohistochemical techniques. RESULTS: Following SCI, dorsal horn SP immunoreactivity demonstrated a profound decrease compared with control tissue, indicating the loss of SP with SCI. A marked increase in perivascular NK1 staining was demonstrated after SCI compared with control levels. No obvious change in claudin-5 immunoreactivity was present immediately following injury, however, by 1 week post-SCI, decreased levels were noted. CONCLUSION: This study demonstrates that severe acute traumatic human SCI results in decreased SP and an immediate increase in NK1 receptor immunoreactivity, suggesting that there is a neurogenic inflammatory component following human SCI.
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Receptores de Neuroquinina-1/metabolismo , Traumatismos de la Médula Espinal/metabolismo , Sustancia P/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Niño , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
We report an encephalomyelopathy in three 18-month-old Merino sheep with features of adult-onset Alexander's disease (AD), a human primary astrocytic disorder. The signature histologic finding was the presence of numerous hypereosinophilic, intra-astrocytic inclusions (Rosenthal fibers), mainly in perivascular, subpial, and subependymal sites, especially in the caudal brain stem and spinal cord. Although AD usually results from mutations in the glial fibrillary acidic protein (GFAP) gene, no such mutation was detected in these sheep. However, the annual clinical presentation of this disorder in a few sheep in the affected flock is suggestive of a familial pattern of occurrence.
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Enfermedad de Alexander/veterinaria , Astrocitos/patología , Proteína Ácida Fibrilar de la Glía/metabolismo , Enfermedades de las Ovejas/patología , Cadena B de alfa-Cristalina/metabolismo , Enfermedad de Alexander/genética , Enfermedad de Alexander/patología , Animales , Astrocitos/ultraestructura , Encéfalo/patología , Enfermedades del Sistema Nervioso Central/genética , Enfermedades del Sistema Nervioso Central/patología , Enfermedades del Sistema Nervioso Central/veterinaria , Diagnóstico Diferencial , Femenino , Proteína Ácida Fibrilar de la Glía/genética , Humanos , Mutación , Embarazo , Ovinos , Enfermedades de las Ovejas/diagnóstico , Enfermedades de las Ovejas/genética , Australia del Sur , Médula Espinal/patologíaRESUMEN
Corynetoxins, members of the tunicamycin group of antibiotics, produce a severe and frequently fatal neurological disorder in ruminant livestock, and guinea pigs are a useful model to study the pathology and pathogenesis of this disease. The aim of this study was to determine whether tunicamycin produced ocular damage in this species, which could have pharmacotherapeutic and diagnostic value. Four 8-week-old guinea pigs were treated with tunicamycin, and two control animals were given the drug vehicle only. Guinea pigs were injected subcutaneously with 400 µg/kg of tunicamycin, in dimethyl sulphoxide, and killed 48 h post-injection. The eyes were then examined by light microscopy. Immunohistochemistry for rhodopsin was also performed. The principal pathological finding was marked retinal photoreceptor damage, which was characterised by disruption and disorganisation of rods, sometimes progressing to necrosis and separation of the outer segment. The cytoplasm of some rods was focally distended by accumulated, proteinaceous material. Rhodopsin immunopositivity in injured rods was markedly diminished and associated with shrinkage and shortening of the injured rod's outer segment. Ocular pathology, in the form of reproducible and extensive retinal photoreceptor damage, was found in guinea pigs given tunicamycin, extending the range of species found to be susceptible to this toxic injury. The guinea pig could prove to be a good animal model to test potential therapeutic interventions, and as brain lesions are often minimal and liver pathology non-specific in intoxicated ruminants, any spontaneously arising ophthalmic injury found in these species could be diagnostically useful.
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Células Fotorreceptoras de Vertebrados , Células Fotorreceptoras , Animales , Modelos Animales de Enfermedad , Cobayas , Rodopsina , TunicamicinaRESUMEN
Tumors containing both neuronal and glial components are a rare heterogeneous group with unique features that require further subclassification. The rosette-forming glioneuronal tumor of the fourth ventricle is one of a number of recently described glioneuronal tumors, which has been accorded official WHO nosologic status only in 2007. We describe the clinical and pathologic features of two patients with rare rosette-forming glioneuronal tumors of the fourth ventricle, one of which was associated with dysgenetic tricho-rhinopharyngeal type I syndrome.
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Neoplasias del Ventrículo Cerebral/patología , Neoplasias Neuroepiteliales/patología , Adulto , Astrocitoma/diagnóstico por imagen , Astrocitoma/metabolismo , Astrocitoma/patología , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/cirugía , Neoplasias del Ventrículo Cerebral/metabolismo , Neoplasias del Ventrículo Cerebral/cirugía , Femenino , Humanos , Inmunohistoquímica , Imagen por Resonancia Magnética , Microscopía Electrónica , Neoplasias Neuroepiteliales/metabolismo , Neoplasias Neuroepiteliales/cirugía , Sinaptofisina/metabolismo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
CASE REPORT: The clinicopathological features of a case consistent with large felid leucoencephalomyelopathy are described in a 19-year-old, zoo-based Sumatran tiger in which degenerative vertebral disease, renal insufficiency, diaphragmatic hernia and cataracts were comorbid. The principal presenting sign was ataxia, with concurrent deterioration of vertebral stiffness and vision loss. Histological features included marked destruction of the white matter, the formation of large, bizarre astrocytes and accumulation of numerous foamy macrophages (gitter cells). Immunohistochemical investigation of reactive astrocytes revealed several different cytoplasmic proteins. CONCLUSION: This is the first reported case of large felid leucoencephalomyelopathy in Australia.
Asunto(s)
Animales de Zoológico , Enfermedad de Leigh/veterinaria , Tigres , Animales , Australia , Autopsia , Diagnóstico Diferencial , Enfermedad de Leigh/diagnóstico , Enfermedad de Leigh/patología , MasculinoRESUMEN
The spatiotemporal pattern of cerebral amyloid deposition, detectable as light microscopically recognizable aggregates in an 'amyloid only' transgenic mouse model of Alzheimer's disease, B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax, is reported for the first time in this strain. Monoclonal and polyclonal antibodies were used to detect amyloid deposition immunohistochemically in brains collected from these mice at 3-12 months of age. Amyloid aggregates (20-200 µm) were first found in serial, whole coronal sections of brain at 4 months of age and these increased progressively, plateauing at 11-12 months. They were most abundant in the cerebral cortices, hippocampus, olfactory bulbs, some white matter tracts and the cerebellar molecular layer; no amyloid aggregates were found in the midbrain, brainstem or spinal cord, or in an equivalent number of brains from wild-type mice. Since the parahippocampal gyrus is severely damaged early in the clinical course of human Alzheimer's disease, amyloid aggregates were also assessed in this brain region and a similar temporal course of amyloid deposition was observed. Moreover, in this gyrus, the amount of aggregated amyloid showed no significant difference between left- and right-sided gyri. However, the polyclonal antibody detected a significantly greater amyloid burden than the monoclonal antibody at 3-10 months of age and the reverse was seen at 11-12 months of age. The pattern of amyloid deposition in the parahippocampal gyrus also resembled that found in the entire brain over time, when the latter was quantified by the colour deconvolution method, suggesting that this gyrus is a good marker for more widely distributed cerebral amyloid deposition. This neuropathological characterization will permit better use of the B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax transgenic mouse strain in future studies of Alzheimer's disease pathogenesis, prevention and treatment.
Asunto(s)
Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/genética , Encéfalo/patología , Modelos Animales de Enfermedad , Amiloide/genética , Amiloide/metabolismo , Péptidos beta-Amiloides/metabolismo , Animales , Femenino , Humanos , Ratones , Ratones Transgénicos , Mutación , Presenilina-1/genéticaRESUMEN
Pathological studies of a sural nerve biopsy in a man with Tangier disease presenting as a remitting-relapsing multifocal neuropathy showed abnormalities in the paranodal regions, including lipid deposition (65%) and redundant myelin foldings, with various degrees of myelin splitting and vesiculation (43%) forming small tomacula and abnormal myelin terminal loops (4%). The internodal regions were normal in the majority of myelinated fibres. Abnormal lipid storage was also present in the Schwann cells of the majority of unmyelinated fibres (67%). The evidence suggests that the noncompacted myelin region of the paranode is a preferential site for lipid storage in the myelinated Schwann cell, and that the space-occupying effects of the cholesterol esters leads to paranodal malfunction and tomacula formation as the pathological basis for the multifocal relapsing-remitting clinical course.
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Enfermedades del Sistema Nervioso Periférico/complicaciones , Enfermedades del Sistema Nervioso Periférico/patología , Nódulos de Ranvier/patología , Enfermedad de Tangier/complicaciones , Enfermedad de Tangier/patología , Adolescente , Humanos , Inmunohistoquímica/métodos , Metabolismo de los Lípidos , Masculino , Microscopía Electrónica de Transmisión/métodos , Proteínas de la Mielina/metabolismo , Vaina de Mielina/patología , Vaina de Mielina/ultraestructura , Proteínas de Neurofilamentos/metabolismo , Enfermedades del Sistema Nervioso Periférico/metabolismo , Nódulos de Ranvier/diagnóstico por imagen , Nervio Sural/patología , Nervio Sural/ultraestructura , Enfermedad de Tangier/metabolismo , UltrasonografíaRESUMEN
This study examined the temporal sequence of post-mortem changes in the cerebellar cortical granular and Purkinje cell layers of mice kept at a constant ambient temperature for up to 4 weeks. Nuclei of granule cell microneurons became pyknotic early after death, increasing progressively until, by 7 days, widespread nuclear lysis resulted in marked cellular depletion of the granular layer. Purkinje cells were relatively unaltered until about 96 h post mortem, at which time there was shrinkage and multivacuolation of the amphophilic cytoplasm, nuclear hyperchromasia and, sometimes, a perinuclear clear space. By 7 days, Purkinje cells had hypereosinophilic cytoplasm and frequent nuclear pyknosis. By 2 weeks after death, Purkinje cells showed homogenization, the cytoplasm being uniformly eosinophilic, progressing to a 'ghost-like' appearance in which the cytoplasm had pale eosinophilic staining with indistinct cell boundaries, and nuclei often absent. The results of this study could assist in differentiating post-mortem autolysis from ante-mortem lesions in the cerebellar cortex and determining the post-mortem interval. Moreover, this information could be useful when interpreting brain lesions in valuable mice found dead unexpectedly during the course of biomedical experiments.
Asunto(s)
Autólisis/patología , Corteza Cerebelosa/patología , Células de Purkinje/patología , Animales , Femenino , Inmunohistoquímica , Ratones , Neuroglía/patologíaRESUMEN
Primary gastric Hodgkin's lymphoma is a rarely encountered lesion. Most cases are observed in the course of systemic disease. Other cases have been reclassified in retrospective studies as non-Hodgkin's lymphomas, after the employment of immunohistochemistry. Some Hodgkin's lymphomas may masquerade non-Hodgkin's lymphomas, and vice versa. Therefore, an accurate diagnosis is important, as treatment and outcome differ significantly for these entities. We report a case of primary Hodgkin's lymphoma arising in the stomach of a 46-year-old male, and discuss the diagnostic approach as well as the differentials of Hodgkin's disease in this anatomic site.
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Enfermedad de Hodgkin/patología , Neoplasias Gástricas/patología , Enfermedad de Hodgkin/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/diagnósticoRESUMEN
Cortical neuronal and glial c-fos immunoreactivity has been demonstrated in experimental and human brain injury. c-fos is one of the immediate early genes important in signal transduction linking environmental stimuli to the cellular genome. c-fos immunoreactivity was semi-quantitated in a head impact sheep model using a grid system applied to standard coronal brain sections obtained from 12 impacted and 4 control sheep. Substantial glial and neuronal c-fos immunoreactivity was present in the pericontusional (penumbra) region, but was absent or minimal in the core of the contusion. Apart from these focal changes, c-fos immunoreactivity was diffusely distributed, with greater involvement in the cerebrum on the side of impact. In the cerebellum, Bergmann glia showed prominent c-fos immunoreactivity, while Purkinje cells were consistently immunonegative. c-fos immunoreactivity varied in different regions of the brain (focal and diffuse patterns) in this ovine head impact model.
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Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/veterinaria , Inmunohistoquímica , Proteínas Proto-Oncogénicas c-fos/metabolismo , Animales , Lesiones Encefálicas/patología , Modelos Animales de Enfermedad , Ovinos , Lóbulo Temporal/patología , Factores de TiempoRESUMEN
CASE REPORT: An 18-month-old Angus cow presented with rapidly developing ataxia and subsequently died. The finding of large numbers of axonal spheroids in brainstem nuclei and spinal cord grey matter, bilaterally symmetrical in distribution, was consistent with a histopathological diagnosis of neuroaxonal dystrophy (NAD). Most of the axonal swellings were immunopositive to amyloid precursor protein, suggesting that interruption to axonal flow was important in their genesis. CONCLUSIONS: The topographical distribution of axonal spheroids in the brain and spinal cord in this bovine case closely resembled that found in the ovine neurodegenerative disorder termed NAD, in which axonal swellings are the major pathological feature. This appears to be the first reported case of this type of NAD in cattle. The aetiology of the spheroidal aggregations in this case was not determined. There was no evidence from the case history or neuropathology to indicate whether the axonal spheroids in this case involved an acquired or heritable aetiology.
Asunto(s)
Ataxia/veterinaria , Axones/patología , Tronco Encefálico/patología , Enfermedades de los Bovinos/patología , Médula Espinal/patología , Animales , Ataxia/patología , Encéfalo/patología , Bovinos , Vértebras Cervicales , Resultado Fatal , FemeninoRESUMEN
X-linked Myopathy with Excessive Autophagy (XMEA) affects proximal muscles of the lower extremities and follows a progressive course reminiscent of muscular dystrophy. It is caused by mutations in VMA21 whose protein product assembles lysosomes' proton pumps. All XMEA mutations to date have been single-nucleotide substitutions that reduce VMA21 expression, which leads to modest lysosomal pH increase, the first step in the disease's pathogenesis. We now report a new class of XMEA mutations. We identified two VMA21 non-coding microdeletions, one intronic (c.54-16_54-8del), the other in the 3'UTR (c.*13_*104del). Both resulted in a relatively more severe (early ambulation loss), diffuse (extra-ocular and upper extremity involvement), and early (neonatal) onset disease compared to previously reported patients. Our cases highlight the importance of including non-coding regions of VMA21 in genetic testing panels of dystrophies and myopathies. Specific diagnosis of XMEA will be particularly important as therapies aimed at correcting the modest rise in lysosomal pH at the root of this disease are developed.
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Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Musculares/genética , Eliminación de Secuencia , ATPasas de Translocación de Protón Vacuolares/genética , Adolescente , Autofagia/genética , Encéfalo/patología , Encéfalo/fisiopatología , Enfermedades Genéticas Ligadas al Cromosoma X/patología , Enfermedades Genéticas Ligadas al Cromosoma X/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Músculo Esquelético/patología , Enfermedades Musculares/patología , Enfermedades Musculares/fisiopatología , ARN Mensajero/metabolismo , ATPasas de Translocación de Protón Vacuolares/metabolismo , Adulto JovenRESUMEN
Axonal injury (AI), as defined by amyloid precursor protein (APP) positive axonal swellings, was recorded on a series of line diagrams of standard brain sections divided into 116 sectors to provide an Axonal Injury Sector Score (AISS) ranging from 0 to 116. This sector scoring method of recording axonal damage and providing a topographic overview of AI was applied to a series of 6 mild head injury cases [Glasgow Coma Scale (GCS) 13-15] and six severe head injury cases (GCS 3-8). The AISS ranged from 4 to 107 overall and varied from 4 to 88 in the mildly injured group and 76 to 107 in the severe head injury group, supporting the concept that there is a spectrum of AI in traumatic head injury and that the AISS is a measure of the extent of AI. APP immunostaining demonstrated positive axonal swellings 1.75 h after head injury and analysis of the pattern of AI in the mild and severe head injury groups showed that axons were more vulnerable than blood vessels and that the axons in the corpus callosum and fornices were the most vulnerable of all.
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Axones/ultraestructura , Traumatismos Craneocerebrales/metabolismo , Traumatismos Craneocerebrales/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Traumatismos Craneocerebrales/fisiopatología , Femenino , Escala de Coma de Glasgow , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana EdadRESUMEN
Amyloid precursor protein (APP) immunocytochemistry was used as a marker for axonal injury (AI) in a series of 16 cases of head trauma associated with fatal falls. Nine cases were falls from not more than the person's own height (falls from < or = own height) and seven cases were falls from a distance greater than the person's own height (falls from > own height). AI was recorded on a series of line diagrams of standard brain sections divided into 116 sectors. AI around focal lesions (infarcts, hemorrhages, contusions) was distinguished from nonfocal axonal injury that was distant from any focal area of damage. The percentage of sectors showing focal AI provided the Focal Axonal Injury Score (FAIS) and the percentage showing nonfocal AI the Non-Focal Axonal Injury Score (NFAIS). The FAIS is a measure of secondary AI and the NFAIS of diffuse axonal injury (DAI). The percentage of sectors involved with AI (focal and nonfocal) provided the cumulative Axonal Injury Score (AIS). A semiquantitative grading system was also used to assess the severity of axonal injury in each sector and the sum of the grades from all sectors was expressed as a percentage to provide the Axonal Injury Severity Score (AISS). Widespread AI was present in all cases irrespective of the height of the fall. AI was present in the midbrain (94%), pons (94%), corpus callosum (100%), central grey matter (100%), and cerebral hemispheric white matter (94%). AIS ranged from 10 to 94 in falls from < or = own height (mean 73) and from 38 to 92 in falls from > own height (mean 82). AISS ranged from 6 to 95 in falls from < or = own height (mean 65) and 28 to 95 in falls from > own height (mean 72). There was no statistically significant difference in AIS or AISS between the two groups. The extent and severity of AI cannot be predicted from biomechanical data, such as the height of the fall, as the total AI in a given case is a variable mixture of Nonfocal AI (DAI) and Focal AI arising by secondary mechanisms, and APP immunostaining is unable to distinguish primary from secondary AI. However, the combination of the Hypoxic-Ischemic Score (HIS) defined as the percentage of sectors showing any hypoxic-ischemic damage ranging from neuronal "red cell change" to infarction in conjunction with the FAIS and NFAIS provided a measure of the relative contribution of primary and secondary AI in a given brain.
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Accidentes por Caídas , Precursor de Proteína beta-Amiloide/metabolismo , Axones/patología , Traumatismos Craneocerebrales/patología , Adulto , Anciano , Anciano de 80 o más Años , Encéfalo/metabolismo , Traumatismos Craneocerebrales/metabolismo , Traumatismos Craneocerebrales/fisiopatología , Femenino , Escala de Coma de Glasgow , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Valores de ReferenciaRESUMEN
In order to determine whether axonal injury (AI) is a factor in cases of penetrating head injury, the brains of 14 patients who died shortly after sustaining a fatal gunshot wound (GSW) to the head were examined, and the presence of AI determined using immunohistochemical staining for amyloid precursor protein (APP). The distribution of AI was mapped throughout the cerebral hemispheres and brain stem. AI was present in all cases in a diffuse distribution distant to the missle track with severe involvement of the brain stem in all cases. There was no axonal APP immunoreactivity in the direct region of the missle track at the point of primary axotomy. The APP-positive AI in these cases is likely to be a mixture of primary and secondary AI as APP immunostaining is unable to distinguish primary AI due to mechanical deformation from AI secondary to hypoxic-ischemic damage.
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Precursor de Proteína beta-Amiloide/análisis , Axones/patología , Química Encefálica , Lesiones Encefálicas/patología , Heridas por Arma de Fuego/patología , Adolescente , Adulto , Axones/química , Biomarcadores , Edema Encefálico/etiología , Edema Encefálico/patología , Lesiones Encefálicas/etiología , Isquemia Encefálica/etiología , Isquemia Encefálica/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Heridas por Arma de Fuego/complicacionesRESUMEN
The aim of this study was to assess and quantitate topographically the effects of posttraumatic intravenous magnesium sulphate (MgSO4) on neuronal perikaryal APP antigen and messenger RNA (mRNA) expression in sheep brains 2 h after a controlled focal head impact. The percentage brain area with APP immunoreactive neuronal perikarya was 71, 56, 27.5 and 5.5%, respectively, in MgSO4-treated head-injured animals, head-injured animals without any treatment, MgSO4 treated nonimpacted animals, and nontreated nonimpacted control sheep. Although there was no statistically significant difference in APP immunoreactive neuronal perikarya in the MgSO4-treated HI group (mean 71%) compared to the HI group without any treatment (mean 56%), northern analysis showed that there was a 2.3-+/-0.2-fold increase in APP mRNA in the thalamus of treated impacted animals compared to untreated impacted animals (p < 0.005). However, MgSO4 treated nonimpacted control animals also showed a 1.6-+/-0.1-fold increase in APP mRNA compared to untreated nonimpacted controls (p < 0.005). MgSO4 therapy results in upregulation of neuronal APP mRNA and APP expression that is quantitatively greater following a focal head impact.
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Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Lesiones Encefálicas/tratamiento farmacológico , Lesiones Encefálicas/metabolismo , Sulfato de Magnesio/uso terapéutico , Neuronas/metabolismo , Animales , Northern Blotting , Femenino , Hibridación in Situ , Ovinos , Regulación hacia ArribaRESUMEN
Axonal injury (AI), one of the principal determinants of clinical outcome after head injury, may evolve over several hours after injury, raising the future possibility of therapeutic intervention during this period. A new head impact model of AI in sheep was developed to examine pathological and physiological changes in the brain resulting from a graded traumatic insult. In this preliminary study 10 anesthetized and ventilated Merino ewes were used. Head injury was produced by impact from a humane stunner to the temporal region of an unrestrained head. Eight sheep were studied for 1, 2, 4, or 6 h after impact. Two sham animals (no impact, 6 h survival) were also examined. Arterial blood pressure, intracranial pressure, and cerebral blood flow were monitored continuously. A physiological index of injury severity was calculated by weighting the percentage shift from preinjury values for each monitored parameter over the first hour after injury. Immunostaining with amyloid precursor protein (APP) was used as a marker of axonal damage and the distribution of APP positive axons was recorded according to a sector scoring method (APPS). Widespread AI was identified in 7 of the 8 impacted animals, around cerebral contusions and in hemispheric white matter, central gray matter, brain stem, and cerebellum, and was detected as early as 1 h after injury. The degree of axonal injury (APPS) correlated well with an index of physiological response to injury (r = 0.83, p = 0.005).
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Axones/fisiología , Traumatismos Craneocerebrales/patología , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Axones/metabolismo , Axones/ultraestructura , Análisis de los Gases de la Sangre , Encéfalo/patología , Traumatismos Craneocerebrales/metabolismo , Traumatismos Craneocerebrales/fisiopatología , Femenino , Hemodinámica/fisiología , Inmunohistoquímica , Presión Intracraneal/fisiología , Ovinos , Hemorragia Subaracnoidea/patología , Factores de TiempoRESUMEN
The effect of global system for mobile communication (GSM) radiofrequency fields on vascular permeability in the brain was studied using a purpose-designed exposure system at 898.4 MHz. Mice (n= 30) were given a single far field, whole body exposure for 60 minutes at a specific absorption rate of 4 W/kg. Control mice were also sham-exposed (n = 10) or permitted free movement in a cage (n = 10) to exclude any stress-related effects. Vascular permeability changes were detected using albumin immunohistochemistry and the efficacy of this vascular tracer was confirmed with a positive control group exposed to a clostridial toxin known to increase vascular permeability in the brain. No significant difference in albumin extravasation was detected between any of the groups at the light microscope level using the albumin marker.