Microscopic Examination Of Brain Research Articles

Современный подход к диагностике патогенетических вариантов ишемического инсульта при атеросклерозе и артериальной гипертонии

The angio- and neurovisualization methods vigorously developing in recent decades determine the relevance of improvement of etiopathogenetic ischemic stroke classification used for the treatment tactics selection and for secondary prevention of the disorder. The study was aimed to clarify the capabilities of clinical diagnosis for pathogenetic variants of ischemic stroke. For that, in 125 postmortem cases, the macro and microscopic examination of brain and cardiovascular system was carried out in order to verify the stroke pathogenesis established as a result of the previous patients’ examination. The study demonstrates the great potential of the major pathogenetic stroke subtypes (large-artery atherosclerosis, cardioembolism, small-artery occlusion) diagnosis using the complex of contemporary clinical and instrumental methods and the main morphological criteria of these subtypes in accordance with the TOAST classification. Moreover, the clinical and pathomorphological assessment allowed us to differentiate stroke resulting from various alterations of single cerebral artery, the atherothrombotic occlusion (44% of cases for the subtype), arterio-arterial embolism (13%) and critical stenosis (10%), as well as stroke resulting from cerebrovascular insufficiency (33%), within the “large-artery atherosclerosis” subtype. Thus, the high informativity of the existing examination methods allows for a more differentiated understanding of the cause of ischemic stroke, which is fully in line with modern personalized medicine.

Blood-Brain Barrier Transport, Plasma Pharmacokinetics, and Neuropathology Following Chronic Treatment of the Rhesus Monkey with a Brain Penetrating Humanized Monoclonal Antibody Against the Human Transferrin Receptor.

A monoclonal antibody (mAb) against the blood-brain barrier (BBB) transferrin receptor (TfR) is a potential agent for delivery of biologic drugs to the brain across the BBB. However, to date, no TfRMAb has been tested with chronic dosing in a primate model. A humanized TfRMAb against the human (h) TfR1, which cross reacts with the primate TfR, was genetically engineered with high affinity (ED50 = 0.18 ± 0.04 nM) for the human TfR type 1 (TfR1). For acute dosing, the hTfRMAb was tritiated and injected intravenously (IV) in the Rhesus monkey, which confirmed rapid delivery of the humanized hTfRMAb into both brain parenchyma, via transport across the BBB, and into cerebrospinal fluid (CSF), via transport across the choroid plexus. For chronic dosing, a total of 8 adult Rhesus monkeys (4 males, 4 females) were treated twice weekly for 4 weeks with 0, 3, 10, or 30 mg/kg of the humanized hTfRMAb via a 60 min IV infusion for a total of 8 doses prior to euthanasia and microscopic examination of brain and peripheral organs. A pharmacokinetics analysis showed the plasma clearance of the hTfRMAb in the primate was nonlinear, and plasma clearance was increased over 20-fold with chronic treatment of the low dose, 3 mg/kg, of the antibody. Chronic treatment of the primates with the 30 mg/kg dose caused anemia associated with suppressed blood reticulocytes. Immunohistochemistry of terminal brain tissue showed microglia activation, based on enhanced IBA1 immuno-staining, in conjunction with astrogliosis, based on increased GFAP immuno-staining. Moderate axonal/myelin degeneration was observed in the sciatic nerve. Further studies need to be conducted to determine if this neuropathology is induced by the antibody effector function, or is an intrinsic property of targeting the TfR in brain. The results indicate that chronic treatment of Rhesus monkeys with a humanized hTfRMAb may have a narrow therapeutic index, with associated toxicity related to microglial activation and astrogliosis of the brain.

Failure of Inositol Trispyrophosphate to Enhance Highly Effective Radiotherapy of GL261 Glioblastoma in Mice.

Inositol trispyrophosphate (ITPP), reported to cure hepatomas in a preclinical rat model and to have beneficial effects in several other solid tumor models, is currently in clinical trial for liver cancer. We investigated whether aggressive glioblastomas could be effectively treated with ITPP alone or in combination with radiation therapy (RT). C57Bl/6 mice were intracranially injected with syngeneic GL261 glioblastoma cells and treated with hypofractionated radiation (5 Gy × 3), ITPP, or both. Tumors were followed by imaging, and mice sacrificed due to morbidity or at 90 days, with microscopic examination of brain sections. RT alone significantly prolonged survival, whereas ITPP alone did not. Surprisingly, ITPP appeared to reduce the effectiveness of RT when added in combination. ITPP was ineffective as monotherapy for glioblastoma and appeared to interfere with the beneficial impact of RT.

Spontaneous lesions and other unusual cell types in bovine brain

The brain in animals suffers with various infectious and non-infectious causes, resulting in overlapping pathological lesions and clinical signs. Therefore, gross and microscopic examination of brain is essential to record lesions and other specialized structures, which are often confused with inflammatory lesions. In the present study, out of 38 intact brain (21 cattle and 17 buffaloes) samples examined, 3 (2 cattle and one buffalo) showed gross lesions, characterized as a circular circumscribed solid mass occupying the white and grey matter in mid cerebrum (1 cattle), a hard calcareous mass adjacent to the hippocampus at the level of the mid cerebral hemisphere (1 buffalo), and a grey colour mass within the cerebrum at the level of fornix (1 cattle). In all the brains processed, involving 7 designated sites, microscopic lesions included: the vascular engorgement (27 cases), hemorrhages (14 cases), peri-vascular cuffing (5 cases), neuronal degeneration (9 cases) and gliosis (5 cases), perineuronal oedema (3 cases), multiple aqueducts (1 case) and unusual normal structures (islands of Calleja cells - 3 cases, external granule cells - 1 case, unidentified bodies resembling corpora amylacea - 1 case). These lesions were distributed in the cerebellum (20 cases), brainstem (18 cases), cerebral hemisphere/caudate nucleus (18 cases), thalamus (16 cases) and in the hippocampus (10 cases). However, 8/38 brains did not show any microscopic lesions. The etiological diagnosis in all the spontaneous cases could not be made and required a thorough investigation in cases having lesions of gliosis, perivascular infiltration and degeneration of neurons. During routine examination of brain tissue, thorough knowledge of neuroanatomy is essential to distinguish normal structures, unusual cells and artifacts that are confused with actual lesions.

Cerebellar ataxia in sheep grazing pastures infested with Romulea rosea (onion grass or Guildford grass)

There have been anecdotal reports since 1962 of 'staggers' in sheep grazing Romulea rosea infested pastures, but this is the first detailed account. In September 2005, a locomotor disorder developed in 12 of 120 Merino wethers that had grazed R. rosea infested pasture at Albury, New South Wales, over several months. Affected sheep displayed signs that included limb paresis, knuckling over in the fetlocks, fine head tremor, incoordination, and an equilibrium disturbance characterised by frequent falling. The microscopic examination of brain and spinal cord tissues from two affected sheep revealed mild vacuolation, occasional lymphocytic cuffing around blood vessels, mild Wallerian degeneration, and occasional glial cells that contained honey-brown cytoplasmic pigments. The most significant changes were found in the cerebellum, where there were decreased numbers of Purkinje cells, increased numbers of glial cells, scattered vacuoles and occasional swollen axons. Previous reports of cerebellar toxicoses in ruminants have involved goats and cattle and have been associated with the ingestion of six Solanum spp. The Purkinje cell loss in this type of disorder is ultimately extensive and consequently affected animals may survive, but will remain permanently disabled.

Transmissão congênita de Babesia bovis

A case of prenatal Babesia bovis infection in Brazil in a 17 year-old Holstein ´ Brown Swiss cow which aborted at approximately eight months of gestation is described and discussed. The newborn calf outlived for few minutes and then died. At necropsy, the thoracic and abdominal cavities were filled by a great volume of a transparent liquid and petechial hemorrhages in oral mucosa and epicardium were observed. Histopathologic examination stained by Haematoxylin-Eosin of lungs, spleen, liver, kidneys, brain and cerebellum revealed variable degrees of congestion and edema, particularly in the liver and brain. In the liver, inflammatory multi-nucleated cells were seen surrounding the portal area and a reasonable degeneration was noted. The brain also revealed endothelium reaction, multi-located hemorrhagic areas in blood vessels and neuronal degeneration. The diagnosis was based on necropsy and microscopic examination of brain that showed B. bovis in the capillary vessels in imprints by Giemsa.

Transneuronal spread of Semliki Forest virus in the developing mouse olfactory system is determined by neuronal maturity

Many neurotropic virus infections have been shown to be virulent in neonatal and suckling mice but avirulent in weaned mice. The neurotropic alphavirus Semliki Forest virus is a well-studied example of this and importantly the age-related change in neurovirulence of this virus has been shown to be independent of specific immune responses. During the first two postnatal weeks many major physiological changes including axonogenesis, synaptogenesis and myelination occur within the rodent CNS. To investigate whether these changes affect virus replication, spread and virulence we have studied the course of infection in the mouse olfactory system. The olfactory system is well-characterized with regard to its development and neuroanatomy and represents an important route of entry of many neurotropic viruses. Following Semliki Forest virus infection, mice younger than 14 days-of-age died from a fulminant panencephalitis, whilst those 15 days and older survived and cleared the infection. Microscopic examination of brains from mice inoculated intranasally either bilaterally or unilaterally and stained by in situ hybridization to detect viral RNA revealed spread of infection along neurites in a circuit-specific manner. Spread in the main olfactory bulb and to primary, secondary and tertiary olfactory connections was observed. In neonatal mice virus rapidly spread throughout the olfactory system and the temporal progress of the infection correlated with the known connectivity patterns of this system. Both anterograde and retrograde axonal spread were observed. During the first three postnatal weeks the rate and extent of virus spread decreased with increasing age. Spread of infection between specific structures was closely related to neuronal maturation. As olfactory system connections matured transmission of virus was curtailed. In mice inoculated at six weeks or six months-of-age infection was minimal in and rarely observed beyond the continually renewed olfactory nerve layer. The ability of this virus to replicate and, or spread in the CNS is clearly linked to neuronal maturation.

Treatment of experimental cryptococcosis with SCH 39304 and fluconazole

The efficacy of two triazoles, SCH 39304 and fluconazole, in the treatment of disseminated cryptococcosis in Wistar rats was determined. A total of 160 rats were inoculated intracardiacally with 2 x 10(5) cells of Cryptococcus neoformans. Both drugs were administered by gavage once daily, at three doses (8, 16, and 32 mg/kg/day). Two treatment schedules were followed: (i) treatment began 1 week after infection and continued for 3 weeks and (ii) prophylaxis treatment began 3 days before infection and continued an additional 3 weeks. Evaluation was based on (i) macroscopic examination of lungs, (ii) microscopic examination of brains and lungs, (iii) histopathology of brains and lungs, and (iv) determination of number of CFU in brains. The number of CFU was the best measure of activity. SCH 39304 was more active than fluconazole in both regimens, and, prophylactically, SCH 39304 was able to achieve biological cures.

Computer-aided morphometric data collection, mapping, and analysis for neuropathologists

Neurologic diseases are frequently characterized by morphologic changes in neuronal tissue. Neuropathologists evaluate such changes by microscopic examination of brain and other tissues. This paper provides an overview of a microcomputer-based image acquisition and analysis system interfaced to an automated microscope directed at aiding neuropathologists in evaluating neuropathologic alterations. Information is provided on general system architecture and function. Details are provided on measurement techniques, key morphologic parameter calculations, data display, and analysis.

Sodium chloride poisoning in cattle.

Consumption of a sodium chloride based supplement followed by food and water restriction in yards for over 30 hours, resulted in nervous disorders in 5 of 60 three-year-old steers within hours of being released into a paddock. Clinical signs were associated with polioencephalomalacia which was confirmed in 2 of 3 affected steers by microscopic examination of brains. Oedema of the corpus striatum, thalamus and midbrain was observed in 2 animals, and vascular necrosis with neutrophil invasion into the vessel walls was seen in the cerebrum of one steer. Consideration of the history, clinical signs and necropsy findings resulted in a diagnosis of indirect salt poisoning. The affected animals had the lower body weights in the group.

Experimental alterations of certain colloidal properties of blood during cardiopulmonary bypass.

Microscopic examination of brain, kidney and lung tissues from patients whose unexplained deaths occurred shortly following cardiopulmonary bypass procedures have revealed varying degrees of systemic fat embolization. Similar findings have been observed experimentally in animals when cardiopulmonary bypass has been maintained by a stationary screen oxygenator for prolonged periods. These findings were not altered by changes in the heparin level, the utilization of protamine or by the type of anesthetic agent employed. Animals receiving replacement transfusions of blood, which had circulated in the pump-oxygenator for 2 hours, demonstrated large quantities of peripheral fat emboli. However, very few fat emboli were found if the oxygenator was omitted from the circuit. Submitted on May 28, 1959