Laminar Lesions Research Articles

Laminar lesions in horses with systemic oxidative stress, committed by experimentally induced or naturally occurring gastrointestinal disorders

Abstract: Laminitis in horses can be associated with lesions in multiple organs secondary to sepsis. Twenty-one horses suffering from gastrointestinal disorders were used in the experiment; 7 horses with experimentally induced endotoxemia and intestinal ischaemia, and 14 horses suffering from naturally occurring colic syndrome. Tissue samples of lungs, liver, heart, brain, cerebellum and hoof laminar tissue were collected for histopathological and oxidative stress evaluation using nitrotyrosine and superoxide dismutase (SOD2) immunostaining. The horses were divided into two groups: the non-oxidative lesions group (NOLG), with 7 horses showing weak immunostaining in lungs, liver and kidney, and the oxidative lesions group (OLG), with 14 horses showing immunostaining indicating systemic oxidative stress in multiple organs. The horses from OLG showed increase of laminar lesions and SOD2 immunostaining in multiple organs when compared to the horses from the NOLG. No differences were found ln regard to laminar immunostaining by nitrotyrosine and SOD2 between experimental groups. It was concluded that systemic oxidative stress can be associated with the development of laminar lesions, and that the laminar tissue does not respond to oxidative stress with increase of SOD as occurs in other organs.

An update on equine laminitis

ABSTRACT: Laminitis is a severe podal affection, which pathophysiology remains partially renowned. Ischemic, enzymatic, metabolic and inflammatory mechanisms are connected to the development of laminar lesions. However, few therapeutic measures are effective to prevent or control the severity of acute laminitis and its prodromal stage, which often determines serious complications such as rotation and/or sinking of the distal phalanx and even the loss of hoof. The purpose of this study is to compile the actual knowledge in respect to the pathophysiology and treatment of equine laminitis.

Oxidative stress in hoof laminar tissue of horses with lethal gastrointestinal diseases

Tissue damage caused by oxidative stress is involved in the pathogenesis of several diseases in animals and man, and is believed to play a role in the development of laminitis in horses. The aim of this study was to investigate the oxidative stress associated with laminar lesions in horses with lethal gastrointestinal disorders. Laminar tissue samples of the hoof of 30 horses were used. Tissue samples were divided as follows: six healthy horses (control group—CG), and 24 horses that died after complications of gastrointestinal diseases (group suffering from gastrointestinal disorders—GDG). Superoxide dismutase (SOD2) and nitrotyrosine immunostaining and the severity of laminar lesions were evaluated. Presence of laminar lesions and immunostaining for nitrotyrosine and SOD2 were only evident in horses from the GDG group. Thus, oxidative stress may play a role in the pathogenesis of laminar lesions secondary to gastrointestinal disorders.

Systemic leukopenia, evaluation of laminar leukocyte infiltration and laminar lesions in horses with naturally occurring colic syndrome

The present study was aimed at identifying laminar lesions and leukocyte infiltration in hoof laminar tissue of horses with colic syndrome and its correlation with the total leukocyte count before death. Six healthy horses were used as control group (CG), and eighteen horses with lethal gastrointestinal disease were divided into two groups: leukopenic group (LG) with seven leukopenic horses, and non-leukopenic group (NLG) with 11 horses with total leukocyte count within reference range for the species. Leukocyte infiltration was examined by immunohistochemistry. Laminar lesions were observed in both LG and NLG, with no differences in severity between them. LG showed increase of the leukocyte infiltration in the hoof laminar tissue, when compared to CG and NLG. Horses with severe colic syndrome (LG and NLG) developed intense laminar lesions without clinical signs of laminitis, with increased leukocyte infiltration. However, the LG demonstrated an even higher increase of leukocyte infiltration compared to both CG and NLG.

Laminar infarcts in clinical routine: a prospective analysis in standard stroke unit patients

The present study aimed to investigate prospectively the frequency of laminar infarcts (LI) within a standard stroke unit population. Laminar infarcts follow neuroanatomical borders rather than the vascular architecture. The LI are rarely noticed in clinical routine because they are typically not detected by computed tomography. As there is a lack of systemic studies about this specific infarct pattern, little is known about their frequency, clinical characteristics or pathophysiological mechanisms. Consecutive acute ischemic stroke unit patients were prospectively enrolled during a 12 month period. The LI were defined as ischemic lesions following the gyral anatomy of the cerebral cortex. The clinical assessment included a standardized questionnaire, clinical syndromes and standard diagnostic results. There were 491 consecutive ischemic stroke patients enrolled (243 female, mean age 75 ± 12 years). The MRI revealed no laminar lesion crossing vascular territories and 28 patients with LI non-crossing vascular territories (7 %). According to the TOAST classification, 61 % of LI were classified as stroke of undetermined etiology (TOAST V) including 46 % with completed evaluation (TOAST Vb). In contrast to these findings, only 20 % of the whole study cohort with non-laminar infarcts were classified as TOAST V. The results indicate that LI are rare. In clinical routine, patients with LI require particular attention. Within the TOAST classification, this specific infarct pattern seems to be underrepresented.

Fra-2 transgenic mice as a novel model of pulmonary hypertension associated with systemic sclerosis

ObjectiveSystemic sclerosis-associated pulmonary arterial hypertension differs from idiopathic pulmonary arterial hypertension with respect to histopathology, treatment responses and survival. Medical progress on PAH is hampered by the lack of human...

Effects of Intracecal Buffer Solution Treatment in Apoptosis of Epidermal Lamellar Cells in Horses With Experimental Laminitis

s Vol 30, No 2 (2010) 113 Laminar arteries, digital arteries and digital veins from BWHE or CHO horses and laminar or digital arteries and veins from control or LPS horses did not possess basal tone. DISCUSSION, CLINICAL RELEVANCE & CONCLUSION The results are consistent with laminitis being associated with vascular dysfunction that is confined to the small veins within the laminar dermis. Since LPS-infusion did not result in the development of basal tone in laminar veins (yet still caused a marked leukopenia) may explain why endotoxemia may not be sufficient to induce laminitis. Effects of Intracecal Buffer Solution Treatment in Apoptosis of Epidermal Lamellar Cells in Horses With Experimental Laminitis Adriana H. Souza, DVM, PhD, Carlos A.A. Valadao, DVM, PhD, Jose Henrique S. Borges, DVM, PhD, Andrea del Pilar Uribe Dias, DVM, PhD, Rafael R. Faleiros, DVM, PhD, Daniel B. Paulsen, DVM, PhD, Ashley M. Stokes, DVM, PhD, and Rustin M. Moore, DVM, PhD., Department of Veterinary Surgery and Medicine-FCAVSao Paulo State University, Jaboticabal, SP 14884-900, Brazil (Souza, Valadao, Borges, Dias); Department of Veterinary Clinics and Surgery, School of Veterinary – Federal University of Minas Gerais, Belo Horizone, MG, 30123-970, Brazil (Faleiros); Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803 (Paulsen) , Equine Health Studies Program, Department of Veterinary Clinical Sciences , School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803 (Stokes) and Department of Veterinary Clinical Sciences, The Ohio State University, Veterinary Teaching Hospital, Columbus, Ohio 43210 (Moore) TAKE HOME MESSAGE Decreased apoptotic cells number in buffered laminitic group shouldbeconsidered an important result of this study. INTRODUCTION Apoptosis is a regulated and controlled process, and its occurrence during diseases has been investigated. We compared apoptotic epidermal cells in the equine laminae during development of CHO-induced laminitis when saline or buffer solution was administrated intracecally. MATERIAL AND METHODS Experimental groups were: control (WS); buffer control (WB); CHO-induced laminitis (CS); and CHO-induced laminitis with buffer (CB). Buffer was administrated 8 hrs after CHO. Apoptosis evaluation in lamellar tissues was made by TUNEL technique and immunohistochemistry (caspase-3; -14). One way ANOVA followed by StudentNeuman-Keuls test analyses were performed (P < 0.05). RESULTS TUNEL-positive basal layer cells were 7.5 and 3.5 times greater in CS and CB groups compared with the control group. TUNEL-positive keratinocytes were 3 and 2 times in CS and CB groups compared with control group. Apoptosis of TUNEL-positive basal layer cells was confirmed by caspase-3 staining. TUNEL-positive keratinocytes did not present staining to caspase-3 or -14. DISCUSSION Increased apoptosis of basal layer cells should be expected due to bacterial components released during developmental phase of the laminitis. These exotoxins are able to activate MMP-2 and MMP-9 in lamellar tissue of laminitic horses. These enzymes increase apoptosis during tissue remodeling and neoangiogenesis. CLINICAL RELEVANCE Since cecal metabolic alterations have importance on the CHO-induced laminitis, the intracecal buffer administration may be useful in laminitis management. CONCLUSION Increased apoptotic basal layer cells in laminitic horses suggest that apoptosis participates in laminar lesions. The role of TUNEL-positive keratinocytes needs to be clarified.

Assessment of pelvic endometriosis: correlation of US and MRI with laparoscopic findings

The purpose of this study was to evaluate the contribution of ultrasound (US) and magnetic resonance (MR) imaging in the diagnosis and local staging of endometriosis by comparing results with laparoscopic findings. We evaluated 36 consecutive women with suspected or clinically diagnosed endometriosis. Thirty-two out of 36 patients met the following inclusion criteria: transabdominal and endocavitary (US) examination and MR imaging, followed by laparoscopy performed within 2 weeks. US and MR findings were classified based on location, number and morphology (small nodules, large nodules, laminar lesions, cystic lesions, complex lesions, adhesions, cul-de-sac obliteration). Laparoscopy, considered the gold standard, identified 143 lesions in 32 patients. US detected 101 lesions, and MR detected 92 lesions, which were subsequently divided by morphologic appearance. Sensitivity and specificity of the two imaging techniques in the recognition of the different locations were 58% and 25%, respectively, for US and 56% and 50%, respectively, for MR imaging. Results of the two techniques in the different locations examined were similar, with the exception of lesions in the rectovaginal septum, which were better detected by US, and for adhesions and cul-de-sac obliteration, which were more easily detected by MR. Both US and MR are accurate in the diagnosis of endometriosis. There are no significant differences in staging of pelvic endometriosis between US and MR. US examination is the primary evaluation in cases of suspected disease and for the rectovaginal septum. MR examination is recommended for correct classification in doubtful cases and in cases of suspected extrapelvic lesions and adhesions.

Utilização de hidrocortisona em eqüinos submetidos a isquemia e reperfusão no jejuno e suas conseqüências sobre o cório laminar

Estudou-se o efeito da administração de succinato sódico de hidrocortisona (SSH) no desenvolvimento de lesões no cório laminar de eqüinos. Doze animais foram submetidos à laparotomia sob anestesia geral e à isquemia total em dois segmentos do jejuno, enquanto três foram usados como controle. Após uma hora de isquemia, seis animais receberam 4,0mg/kg de SSH por via intravenosa (grupo T) e seis receberam placebo (grupo NT). Após duas horas de isquemia foi restabelecido o fluxo de sangue local e, decorridas duas horas de reperfusão, foi realizada a laparorrafia e permitiu-se a recuperação anestésica. Após 12 horas do início da reperfusão, os animais foram sacrificados e deles colhidas amostras de tecido laminar para avaliação histomorfológica. As alterações avaliadas ao microscópio óptico foram quantificadas por escores que variaram de 0 a 3. Os escores para lesão no tecido laminar foram semelhantes nos animais dos grupos T (0,41) e NT (0,54), permitindo concluir que a hidrocortisona não acentuou as lesões produzidas no tecido laminar após a isquemia e reperfusão no jejuno.

Submural histopathologic changes attributable to peracute laminitis in horses.

To describe submural histopathologic changes attributable to peracute laminitis in horses. 20 adult horses. A concurrent-control design was used to compare laminar lesions in 10 horses subjected to carbohydrate-induced laminitis with laminar characteristics of 10 sex- and aged-matched control horses with normal feet. Horses in the treatment group were administered an overload of carbohydrate. Tissues were obtained by biopsy 4 to 8 hours after onset of lameness or 72 hours after administration of the carbohydrate overload when lameness did not develop. Sections were stained with H&E, Masson's trichrome, and periodic acid-Schiff stains. Histopathologic changes were analyzed to detect differences between groups and to correlate epidermal changes with severity and duration of lameness. Analysis indicated that dermal and epidermal lesions were evident despite lack of visible separation of the epidermal basement membrane, can be found in horses without detectable lameness, and were nonspecific and progressive following onset of lameness. Furthermore, severity and location of lesions were associated with severity and duration of lameness. These observations are consistent with the concept that separation of the laminar epithelial basement membrane is a delayed step in the pathogenesis of acute laminitis, digital vascular hypoperfusion is an underlying cause for laminitis, and the potential for repeated episodes of subclinical laminitis may underlie the development of structural and mechanical changes consistent with chronic laminitis despite lack of clinical signs of acute laminitis.

Cortical laminar necrosis in brain infarcts: chronological changes on MRI.

We studied the MRI characteristics of cortical laminar necrosis in ischaemic stroke. We reviewed 13 patients with cortical laminar high signal on T1-weighted images to analyse the chronological changes in signal intensity and contrast enhancement. High-density cortical lesions began to appear on T1-weighted images about 2 weeks after the ictus. At 1-2 months they were prominent. They began to fade from 3 months but could be seen up to 11 months. These cortical lesions showed isointensity or high intensity on T2-weighted images and did not show low intensity at any stage. Contrast enhancement of the laminar lesions was prominent at 1-2 months and became less apparent from 3 months, but could be seen up to 8 months.

Amyotrophic lateral sclerosis and parkinsonism-dementia from Guam: differences in neurofibrillary tangle distribution and density in the hippocampal formation and neocortex

Amyotrophic lateral sclerosis/parkinsonism-dementia complex is a highly prevalent neurodegenerative disorder among the native Chamorro population of Guam, and is characterized by widespread formation of neurofibrillary tangles. In the present study, the distribution of neurofibrillary tangles was quantitatively assessed in the cerebral cortex of cases presenting with either predominant amyotrophic lateral sclerosis or parkinsonism-dementia symptomatology. Results show that although the regional and laminar lesion distribution is qualitatively similar in both groups, cases with predominant parkinsonism-dementia generally have higher lesion densities than cases with amyotrophic lateral sclerosis. Interestingly, layer II of the entorhinal cortex was affected to the same degree in both conditions. In both groups, the CA1 field of the hippocampus, subiculum, and entorhinal cortex were the most affected areas. In the neocortex, the perirhinal and inferior temporal cortex consistently had higher lesion densities than the frontal, parietal, and cingulate cortex, whereas the visual cortex was practically devoid of lesions. Also, most of the neurofibrillary tangles were located in the supragranular layers of the neocortex, with relatively low densities in the infragranular layers, in both brain groups. Interestingly, the primary motor cortex contained more neurofibrillary tangles in parkinsonism-dementia than in amyotrophic lateral sclerosis cases. It is possible that the differences in regional neurofibrillary tangle densities reflect the variable severity of the dementing process observed between the two groups of patients. Several studies on Alzheimer's disease and related disorders indicate that the regional and laminar cortical localization of neurofibrillary tangles may parallel the degeneration of specific corticocortical projections. The present data suggest that the population of corticocortical projections involved in Guamanian cases differs substantially from that affected in Alzheimer's disease. The differential distribution and densities of the lesions may contribute to the differences in symptomatology and severity of dementia among Alzheimer's disease and Guamanian cases, although these neurodegenerative disorders as well as related illnesses may share certain etiopathogenetic mechanisms.

Lateral hyperstriatal lesions disrupt simultaneous but not successive conditional discrimination learning of pigeons (Columba livia).

In 2 experiments we explored the effects of lateral versus medial laminar lesions of the hyperstriatum in pigeons (Columba livia); medical lesions were largely confined to the hyperstriatum accessorium, and lateral lesions to the hyperstriatum dorsale and hyperstriatum ventrale. In Experiment 1, lateral, but not medial, lesions disrupted acquisition of a simultaneous conditional discrimination; both medial and lateral lesions disrupted reversal of the discrimination. The reversal deficits of the medial and lateral groups were quantitatively similar, and both groups showed exaggerated positional responding. In Experiment 2, neither medial nor lateral lesions disrupted acquisition of a successive conditional discrimination. We conclude that lateral hyperstriatal damage does not obtain a general disruption of conditional learning; we speculate that the lateral hyperstriatum may play a critical role in configural learning.

Correlation of dermal-epidermal laminar lesions of equine hoof with various disease conditions.

Dermal and epidermal laminar lesions were correlated with acute intestinal, primary hepatic, septicemic, chronic laminar, and acute laminar diseases. Horses with acute intestinal disease had edema in the secondary dermal laminae. Those with hepatic disease had increased keratinization of the secondary epidermal laminae. Septicemia caused increased keratin formation in the primary and secondary epidermal laminae. Chronic laminitis caused architectural changes of the epidermal laminae characterized by hyperplasia and keratin formation of the basal epidermal layer. Horses with acute laminitis had epidermal necrosis, especially with peracute laminitis. Various insults to the epidermal laminae led to epithelial hyperplasia of the secondary epidermis with ventral deviation of the third phalanx.

Interlaminar connections of the visual cortex in the hedgehog (Paraechinus hypomelas).

The contribution of each cortical lamina to intracortical circuitry was studied in the visual neocortex of the Pakistani hedgehog. Punctate laminar lesions were made electrolytically within the visual cortex, and after five to seven days the brains were processed and stained with the Fink-Heimer technique. The results of this study suggest that both horizontal and vertical connections are important to the organization of visual cortex in the hedgehog. The horizontal projections originate at three distinct cortical depths. Lesions in layer II reveal projections that traverse the inner one-half of layer I; lesions in layers III and IV reveal projections that traverse layer IV and that enter the cortical white matter; lesions in layers V and VI reveal projections that traverse the outer one-half of layer VI and that enter the cortical white matter. The vertical projections are oriented perpendicular to the pial surface. Layers II and III project to underlying layer V. Layers V and VI in turn contribute to a reciprocal projection back to all superficial cortical laminae. This anatomical data about intracortical circuitry is discussed with reference to the functional organization of visual cortex.

An electron microscopic study of dendritic degeneration in the cerebral cortex resulting from laminar lesions.

The morphological characteristics of dendrites in layers of the cerebral cortex above laminar lesions induced by ionizing particle irradiation have been studied in the striate field of rat at various survival times. Within two weeks following irradiation an increasing number of dendrites display unusual alterations inferred to be signs of degeneration. Degenerating dendrites can be characterized by a dense cytoplasmic matrix, disruption of mitochondria, presence of dense bodies, irregular outline and a marked alteration of the plasmalemma in its dimensions and staining properties. Some degenerating dendrites possess a large accumulation of dense subsynaptic material and are contacted by synapses with enlarged and altered synaptic clefts. A few dendrites contain extensive membranous whorls. Engulfment by reactive astrocyte processes is a common feature and often includes the presynaptic axonal knob, but only the degenerating dendrite has been observed within glial cytoplasm. The inference that the majority of degenerating dendrites in this material are apical dendrites of pyramidal cells suggests that either shaft synapses are common for these cells, protuberances may retract during degeneration, or spines are lost due to loss of afferent terminals.

Geniculo-striate connections in the rabbit. I. Retrograde changes in the dorsal lateral geniculate body after destruction of cells in various layers of the striate region.

AbstractDorsal lateral geniculate body was examined for retrograde changes which follow radiation lesions placed in various cortical layers of the striate region. Destruction of cells in a thin cortical strip (less than about 200 μ in stained sections) produces, at most, marginal changes in the dorsal lateral geniculate body regardless of which cortical layer is destroyed. Lesions which are thicker than those mentioned produce, if located in layers 4, 4 and 5 or 5 and 6, definite degenerations. The thicker the lesion the more pronounced are the changes. Destruction of layers 1 to 3 produces, at most, marginal changes. However, degenerations caused by destruction of layers 4 and 5 appear augmented if supragranular layers are concomitantly destroyed. Destructions of layers 1 to 5 produce degenerations of a severity similar to those resulting from destructions of layers 1 to 6. An effective cortical destruction located in some sector of the striate field produces changes in a restricted geniculate region. It is concluded that the survival of cells in a geniculate locus depends upon the entire vertical column of cortical cells rather than on any layer within this column. Implications of the findings as regards the distribution of terminals of the geniculate neurons are considered. The significance of radiation damage to fibers and of fibers sprouting in the laminar lesion for interpretation of the findings is discussed.

Distribution of afferent and efferent fibers in the cerebral cortex of the rabbit revealed by laminar lesions produced by heavy lonizing particles

Patterns of Marchi degeneration following laminar lesions of the cerebral cortex of rabbits were studied in order to delimit the arrangement of afferent fibers. Pericellular nests of Marchi granules above laminar lesions appear to represent the preterminal portion of ascending fibers and the number of such degenerating fibers increased with deeper lesions or higher doses of radiation. Although ascending fiber degeneration can be demonstrated extensively in the supragranular layers, severe disruption of fibers and complete destruction of neurons in these layers does not result in retrograde thalamic atrophy, suggesting that termination in the granular and infragranular layers are sufficient for sustaining thalamic neurons. The Marchi degeneration in the thalamus following lesions of the supragranular layers represents descending degeneration of corticothalamic fibers. Corticothalamic fibers have been shown to arise from all cellular layers of the cerebral cortex, but the largest contribution of these fibers is observed with lesions which involve the infragranular layers. Degeneration traced from the sensorimotor cortical fields to the substantia nigra appears to possess a predominantly infragranular layer origin. Results support the differentiation of the laminar organization of the sensory cortical fields into a predominantly, but not exclusively, afferent role for the granular and supragranular layers, and an efferent role for the infragranular layers.

Long-Term Pathologic and Behavioral Changes in Mice after Focal Deuteron Irradiation of the Brain

An extensive literature has accumulated on histologic, physiologic, and behavioral changes after electromagnetic whole-body and head irradiation (1). However, interpretations of radiobiologic effects on the nervous system have been difficult, owing to the mode of ionizing energy transfer to exposed structures (2, 3). In irradiation of the brain with X-rays, energy absorption may be attenuated exponentially with depth, scattered by collisions, and dispersed in accordance with the distance of the source of irradiation. Attempts to direct such ionizing radiation to discrete regions of the brain may result in additional irradiation of the pituitary and oropharynx, leading in turn to possible indirect effects on the nervous system. Consequently, it has not been feasible to identify and segregate specific radiation effects on brain tissue resulting from direct exposure of nervous tissue, indirect effects due to irradiation of surrounding or adjacent structures, and interaction effects involving a combination of direct and indirect alterations. Efforts to establish primary differential radiosensitivities of neuronal populations independent of secondary changes produced by vascular damage have also been precluded by such direct and indirect effects. More recently, the energy spectrum of ionizing radiation to which the central nervous system has been exposed has been extended considerably with the development of cyclotron-accelerated particles (4-7). In contrast to electromagnetic radiation, cyclotron-accelerated protons, deuterons, and a-particles have a more uniform depth range with minimal scatter and dispersion, permitting irradiation which may be confined to a discrete target tissue producing a laminar lesion within a single cortical layer (8). By using such monoenergetic heavy-particle microbeam irradiation techniques to produce discrete stimulations or radiogenic lesions, it is possible to study direct radiation effects on the central nervous system by: (1) comparing sequences of specific histopathologically demonstrable selective cellular and vascular alterations, (2) ex-

Effects of heavy, ionizing, monoenergetic particles on the cerebral cortex. I. Production of laminar lesions and dosimetric considerations.

A technique is described that was used to produce laminar lesions at different depths of the cerebral cortex in rabbits, cats, and monkeys by means of heavy, ionizing particles delivered in a beam from a 60-in. cyclotron. Dosimetric problems are discussed in detail. Examination of 384 radiation lesions indicated that a laminar lesion was produced by peak doses of 15000 to 45000 rads. The corresponding surface and average doses were 3000 to 9000, and 5000 to 15000 rads respectively. A technique of multiple irradiations with a shift of the zone of maximal ionization is described. Some observations pertaining to the latent period of radiation lesions of the brain and data on the relation between the width of the laminar lesion and the magnitude of the radiation dose are presented and discussed. (C.H.)