Influence of Photodynamic Therapy on Lichen Sclerosus with Neoplastic Background.

BACKGROUND: Lichen sclerosus is the most common nonmalignant vulvar disease with morbidity in postmenopausal age. The first line of treatment is corticosteroid therapy. In case of insufficiency, tacrolimus or pimecrolimus can be provided. Photodynamic therapy (PDT) can be used as alternative way of treatment while symptoms recurrent despite other methods. METHODS: the analyzed population of 182 women with diagnosis of lichen sclerosus treated using PDT was divided into three groups: patients with neoplastic disease or intraepithelial neoplasia; those with a positive family history of neoplastic disease; and a control group with no neoplastic disease and no familial history of neoplastic diseases. RESULTS: Reduction of vulvar changes was assessed in the whole vulva in the groups as 21.9%, 21.2% and 21.8%, respectively. The most frequent symptom, itching, was reported to decrease in all groups, 39.3%, 35.5% and 42.5%, respectively. Improvement of quality of life was assessed in 91.3% of the whole group, stabilization of lichen sclerosus in 7.1% and progression in 1.6%. CONCLUSIONS: Photodynamic therapy gives positive results in most cases. Improvement after PDT is observed in objective vulvoscopic assessment and in subjective patients' opinions. Neoplastic disease in the past can influence the effectiveness of PDT.

Commitment of protein p53 and amyloid-beta peptide (Aß) in aging of human cerebellum.

Protein p53 is known to induce the cell cycle arrest and apoptosis in response to a variety of cellular distress signals and DNA damage. A recent study has demonstrated that in blood cells of aging subjects, p53 may induce early pathological changes that precede the amyloidogenic cascade. However, it is not clear whether p53 participates in the local deposition of amyloid-beta peptide (Aß) in the nerve tissue of normal aging subjects. Therefore, in the present study, we analyse the distribution of both (Aß and p53) proteins in the cerebellum of individuals without any history of dementia or other neurological illness who died suddenly in traffic accidents. We found that in the subjects at the beginning of their aging process (60-65 years of age) Aß deposits were localized in subependymal areas of the cerebellar cortex and such deposits were not linked to the presence of p53 in the nerve tissue. In groups of subjects over 65 years of age, numerous Aß diffuse plaques were scattered throughout the cerebellar cortex. In these subjects, p53 protein was detected in the cytoplasm or in the nucleus of the cerebellar nerve cells. All the results lead to the conclusion that in nerve tissue p53 participates in the process of neurodegeneration and then it is involved in the deposition of A in the nerve tissue.

Toll-like receptor 2 (TLR2) is a marker of angiogenesis in the necrotic area of human medulloblastoma.

Angiogenesis plays a key role in the progression of malignant tumors. In recent years, anti-angiogenic drugs have been shown to be effective against tumors. However, some tumors are able to adopt escape mechanisms, suggesting that the vascular network in these tumors may be formed or may function in a different way. Medulloblastomas are tumors characterized by poor prognosis and low patient survival rates. These tumors rarely metastasize, but the reason why they almost always recur locally is not known. Central to mediating neoplastic changes is the interaction between cell surface receptors and their cognate ligands, which through intracellular signaling induce alternations in gene expression. In this context, the aim of our present study was to examine in medulloblastoma the distribution of Toll-like receptor 2 (TLR2) and receptor for advanced glycosylation end-product (RAGE), and mast cells associated with the tumor neovascularization process. Immunohistochemical study with a battery of specific antibodies was used. The results show that in the tumor necrotic area, TLR2 participates in all steps of vascular network formation, but in regions where the tumor was not affected by necrosis, the capillary network was TLR2 immunonegative. The TLR2 vascular network of the necrotic area was not associated with RAGE and mast cells. However, in the region of the medulloblastoma not affected by necrosis, the RAGE receptor was present in the endothelium of all capillaries, and mast cells were numerous only in the perivascular space of large brain and meningeal vessels at the border of the tumor. In conclusion, our results show that the receptor of innate immunity TLR2 plays an important role in recognition of ligands delivered by dying necrotic medulloblastoma cells and participates in tumor neovascularization. Moreover, the results show that the RAGE receptor and mast cells operate in different medulloblastoma regions and influence different parts of the tumor vascular network.

Methyl-CpG binding protein 2, receptors of innate immunity and receptor for advanced glycation end-products in human viral meningoencephalitis.

Inflammation is a normal host defense reaction to infections and tissue injury. In pathology, the process of inflammation is deregulated by various environmental factors, prolonged activation of Toll-like receptors (TLRs), induction of epigenetic machinery or expression of receptors for advanced glycation end-products (RAGE). In the present study, we examined immunoexpression of proteins participating in the above-mentioned mechanisms, in the brain of patients with viral meningoencephalitis. The results showed that depending on the period of the disease, the process of inflammation is deregulated in different ways. In an early period of viral meningoencephalitis, we found numerous so-called microglial nodules which were strongly immunopositive to methyl-CpG protein 2 (MeCP2). This protein is an epigenetic factor important for methylation of DNA; therefore, our results suggest that cells collected in the nodules may participate in modification of the host defense reaction. Moreover, in the early period of viral meningoencephalitis, we found that Purkinje cells of the cerebellum contain TLR3 or TLR9 receptors that can recognize viral pathogens and may activate a self-destructive mechanism in these neurons. In the later (advanced) period of viral meningoencephalitis, despite some of the above observations, RAGE protein was detected in the brain of adult and aging patients. It means that in this period of the disease, the inflammatory process may be deregulated by numerous post-translationally modified proteins that are transported to the brain after binding with activated RAGE. In addition, young patients appeared more susceptible to viral infections than adult and aging patients, because most of them died during the early period of meningoencephalitis.

Crosstalk in human brain between globoid cell leucodystrophy and zinc-α-2-glycoprotein (ZAG), a biomarker of lipid catabolism.

Zinc-alpha-2-glycoprotein (ZAG) is a protein identified as a lipid-mobilizing factor participating in a lipid catabolism. In spite of intensive studies conducted during last five decades, the role of this protein in processes of neurodegeneration remains unclear. The aim of our study was to examine the presence of ZAG protein in the brain of patients with Krabbe's disease, which is considered as a psychosine lipidosis caused by a mutation of a known gene. We found intracellular and extracellular localization of ZAG in the brain of Krabbe's disease patients but in the brain of control age-matched patients, ZAG was not detected. Distribution of ZAG in the brain suggests that the influx of ZAG into the brain involved a blood-brain barrier mechanism and adenoreceptors localized on astrocytes and some neurons.

Toll-like receptors as an innate immunity bridge to neuroinflammation in medulloblastoma.

The relationship between inflammation, immunity and cancer is widely accepted but mechanisms mediating this relationship remain unknown. Our present study was undertaken to examine the presence and distribution of Toll-like receptors (TLRs) in necrotic areas of medulloblastoma. These receptors fulfil the criteria postulated for the receptors of innate immunity and signalling from TLRs induces synthesis of various pro-inflammatory cytokines, enzymes and mediators. The study was performed on human medulloblastoma samples containing areas of necrosis within the tumour and/or within the normal nerve tissue at the periphery of the tumour. Proteins of four TLRs: TLR 2, 3, 4 and 9 were detected in the tissue with the immunohistochemical method using the specific antibodies. Two types of necrotic areas were found. In the first type, the area of dead cells was surrounded by undifferentiated medulloblastoma cells. A lot of these cells expressed TLR 2 and TLR 3 antigens. TLR 2 was also expressed on the wall of de novo formed blood vessels that fill tumour regions already cleared from dead cells. The second type of necrotic areas were found at the periphery of the tumour and composed of normal nerve tissue cells. TLR 2, TLR 3 and TLR 9 were detected in hypertrophic glia cells. Our findings show a new function of TLRs as sensors of pathogens released by medulloblastoma dead cells. This new function may provide a key link connecting innate immunity, neuroinflammation and angiogenesis in the tumour.

Cerebellar cortical neurons misplaced in the white matter due to disturbed migration during development of human brain.

The normal laminar organisation of the cerebellar cortex is the result of the precisely controlled migration, differentiation and maturation of the neurons. Occasionally the migrating neurons lose their proper way of migration and form nests of grey matter in the improper place. The aim of this study was to investigate the morphological features of the lost neurons in the cerebellar white matter during development, with particular emphasis on their localisation, arrangement and differentiation. We analyzed 31 fetal and infantile brains, aged from 28 gestational weeks to 18 postnatal months. We observed different morphological patterns of cerebellar heterotopias. Clusters of grey matter reflecting the cerebellar cortical pattern with well-defined molecular layer and altered granular and Purkinje cells were most frequently observed. The compact heterotopias were composed of bands or whirls of spindle and round granule cells situated closely together, while Purkinje neurons were completely disorganised. The ectopic cortex in the white matter with a normal layered structure containing all the components of the cerebellar cortex was localised by the large vessels. Aggregations of Purkinje cells scattered in the white matter without accompanying granule cells were observed. The evaluation of the biological features of the misplaced cerebellar cortical components showed high activity of neurons.

Immunodistribution of amyloid beta protein (Aß) and advanced glycation end-product receptors (RAGE) in choroid plexus and ependyma of resuscitated patients.

RAGE (receptor for advanced glycation end-products) participates in the influx transport of glycated Aß (amyloid beta) from the blood to the brain. Because little is known of the RAGE operating in brain barriers such as those in the choroid plexus and ependyma, the aim of the present study was to examine the immunodistributions of RAGE and Aß peptides in the choroid plexus where the blood-cerebrospinal fluid barrier (B-CSF) is located, and in ependyma of the brain ventricles associated with functions of the cerebrospinal fluid-brain barrier (CSF-B). The study was performed on patients over 65 years successfully resuscitated after cardiac arrest with survival a few weeks. The control group consisted of age-matched individuals who were not resuscitated and died immediately after cardiac arrest. In resuscitated patients, but not in controls, RAGE receptors were localized in choroid plexus (CP) epithelial cells and in ependymal cells bordering the brain ventricles. These cells form the B-CSF and CSF-B barriers. The presence of Aß was detected within the CP blood vessels and in the basement membrane of the CP epithelium. In numerous cytoplasmic vacuoles of CP epithelial and ependymal cells Aß protein was found and our observations suggest that the contents of those vacuoles were undergoing progressive digestion. The results demonstrated that CP epithelium and ependymal cells, equipped with RAGE receptors, not only play an important role in the creation of amyloid deposits in the brain but are also places where Aß may be utilized. The RAGE transportation system should be a main target in the therapy of brain amyloidosis, a well-known risk factor of Alzheimer disease.

Association of mast cells with calcification in the human pineal gland.

Increased pineal calcifications and decreased pineal melatonin biosynthesis, both age related, support the notion of a pineal bio-organic timing mechanism. The role of calcification in the pathogenesis of pineal gland dysfunction remains unknown but the available data document that calcification is an organized, regulated process, rather than a passive aging phenomenon. The cellular biology and micro-environmental conditions required for calcification remain poorly understood but most studies have demonstrated evidence that mast cells are strongly implicated in this process. The aim of the present study was to examine the phenotype of mast cells associated with early stages and with the progressive development of calcification in the human pineal gland. The study was performed on pineal samples of 170 fetuses and children whose brains were autopsied and diagnosed during 1998-2002. The representative cerebral and pineal specimens were stained with haematoxylin and eosin or the von Kossa staining technique and for the distribution of mast cell tryptase, mast cell chymase, histamine H4 receptor and vascular network using biotinylated Ulex europaeus agglutinin. Tryptase mast cells were found in all stages of pineal gland development independently of the presence of local tissue lesions. All of them were always localized in the close vicinity of the blood vessels and expressed immunoreactivity to histamine H4 receptor antibody. Immunolocalization of mast cells by chymase antibody (and following dual immunostaining with both chymase and tryptase antibodies) demonstrated that these cells were few in number and were located in the subcapsular region of the gland. In our study, all functional mast cells that underwent activation and were co-localized with deposits of calcium did not contain chymase. All of them were stained with tryptase and represent the MC-T phenotype. Tryptase mast cells and extracellular tryptase were often associated with areas of early and more advanced stages of calcification. Our results lead to the conclusion that the tryptase mast cells play a major role in the pineal calcification process as sites where this process starts and as a source of production of numerous biologically active substances including tryptase that participate in calcification.

Calbindin positive Purkinje cells in the pathology of human cerebellum occurring at the time of its development.

Development of cerebellum continues over an extremely long period of time extending from the early embryonic phase until the first postnatal years. During an extended time of maturation the cerebellum is vulnerable to harmful agents. A group of cytoplasmic proteins that may protect cells against injury are the calcium binding proteins, among others calbindin. The distribution of this protein is not well known in cerebellar pathology, thus in the present study the localisation and appearance of calbindin expressing Purkinje cells in different pathological conditions occurring at the time of cerebellar development was examined. The investigations were carried out on human maturing cerebellar cortex (age range 30 gestational weeks - 2 years) of cases with paraneoplastic cerebellar degeneration and cerebellar neuronal migration disturbances. The Purkinje cells located in cerebellar heterotopias and dysgenesias were morphologically well developed and strongly immunostained with calbindin antibody. In paraneoplastic cerebellar degeneration the progressive decrease of calbindin content and disintegration of Purkinje cells were observed. Our results show that intrauterine harmful agents that disturb migration of the cerebellar neurons do not affect the content of calbindin in misoriented neurons and that this protein may play a role in development of Purkinje cells located in heterotopias and cerebellar dysgenesias. The progressive decrease of calbindin content in the Purkinje cells undergoing degeneration and death during paraneoplastic changes in the cerebellum also supports the hypothesis that this protein is very important component of intracellular homeostasis in cerebellar neurons.

Angiotensin II (Ang II) evoked secretion of the human placental lactogen (HPL) in intrauterine growth retardation: examination of the relationship with Ang II receptor type 1 (AT1) expression.

Angiotensin II (Ang II) and its hemodynamic effects on placental vasculature mediated via Ang II receptor type 1 (AT1) may play significant role in intrauterine growth retardation (IUGR). Placental lactogen (HPL) production directly reflects placental function. We compared influence of Ang II on HPL production in normal and IUGR-complicated pregnancies and correlated this phenomenon with AT1 expression. Basal and Ang II-evoked HPL secretion was examined in perfused placental lobules using ELISA. After immunostaining of placental sections, AT1 expression was estimated using quantitative morphometry. Ang II increased HPL secretion. Ang II-evoked increase in HPL concentration in the perfusion fluid was 27.36+/-6.4 (%, +/-SEM) lower in IUGR (p<0.05) compared to normal-course pregnancies. AT1 expression was significantly decreased in IUGR and was 78.12+/-8.2 (%, +/-SEM) of the mean value of controls. Demonstrating that Ang II-evoked secretion of HPL in preeclampsia-free IUGR is decreased and correlates with down-regulated expression of AT1, we present a new approach to the pathophysiology of IUGR.

Astroglia and microglia in cerebellar neuronal migration disturbances.

Between the neuronal and glial cells there is a close relationship conditioning a tight morphological correlation and proper functional interplay. Disturbed interaction between glial and neuronal components leads to inappropriate neural circuits. The reflection of the failure of neural circuit organisation is the picture of morphological changes of neurons and glia. The appearance of microglia and astroglia was analysed in a defectively formed cellular network due to cerebellar neuronal migration disturbances. Focal disruption of neuron migration leads to their differentiation in an abnormal position manifested as heterotopias and cortical anomalies. Neurons that had lost their proper migratory way and heterotopically settled in the white matter were encircled by GFAP-positive astrocytes, with morphology appropriate for surrounding white matter. The microglial cells infiltrated the parenchyma within the heterotopic neurons playing a role in their elimination. In the cerebellar cortical malformations astrocytes were grouped near the Purkinje cells. In the minimal cortical dysplasia the increased number of astrocytes supported the neurons. Impaired morphological components of the glial-pial barrier were observed. In the massive cortical malformations a few degenerated astrocytes followed the disarranged Purkinje cells, while microglia and Bergmann glia fibres were not present. Absence of cells supporting and organizing the cerebellar cortex had an effect on loss of Purkinje cell shape, their disorientation and abnormal position. The appearance and localisation of the astroglia and microglia in the abnormal cerebellar circuitry due to migration disturbances is dependent on the pathomechanism of the anomalies.

Faulty position of cerebellar cortical neurons as a sequel of disturbed neuronal migration.

The object of our report is the presentation of the morphological picture of cerebellar cortex malformation as a sequel of disturbed neuronal migration. In the disarranged tissue, cavities with a network of meningeal tissue and embedded pathological vessels were noted. The external granule cells did not form a proper external granule layer, but moved deeper, forming irregular aggregates. Abnormally aggregated external granular cells invaded the cerebellar tissue. Abnormal Purkinje cell positioning and a disarranged molecular layer were observed. The normal layered pattern of the cerebellar cortex was disorganized. The presented cases represent a spectrum of morphological changes which are the consequence of aberrant migration. Against a background of vascular pathology affecting the meningoglial network the migration pathways were disrupted. The defective movement of neurons and their faulty maturation resulted in disturbances of cortical layering, and defects of cerebellar folia formation.

Inflammatory and reparative tissue reaction in developing human central nervous system.

Morphologic features of inflammatory reactions in the immature central nervous system (CNS) develop in the second half of pregnancy. The cells composing the infiltrations arise early during development but their presence in circulation and final localization in fully mature inflammatory reactions is prolonged in time. The aim of this work was to compare the picture of inflammatory infiltrations in a group of fetal brains following various infections and aseptic injuries. It was found that numerous granulocytes appeared in bacterial infections, but not in aseptic lesions of the brain. The young maturing blood cells and granulocytes demonstrate the subsequent stages in the development of the inflammatory reaction. The changes depend on the character of the injurious factor and the level of maturation of the CNS. The topography of maturing brain lesions due to infections and anoxic/ischemic damage was similar and localized most often in the periventricular white matter.

Toll-like receptors in rat brains injured by hypoxic-ischaemia or exposed to staphylococcal alpha-toxin.

Some data suggest that the central nervous system (CNS) is the main target of Staphylococcus alpha-toxin. Since this pathogen cannot penetrate the blood-brain barrier (BBB), the exact mechanism by which alpha-toxin affects the CNS remains unclear. Recent studies on the role of the innate immune system have shed light on how bacterial infections initiate inflammatory responses within the CNS. The aim of this study was to investigate the immunoexpression of Toll-like receptors (TLR 2, TLR 4) in brains of young rats systemically exposed to Staphylococcus alpha-toxin or injured by neonatal hypoxia-ischaemia. The study was carried out on 6-week-old Wistar rats. A group of 6-week-old rats with severe brain injury caused by neonatal hypoxia-ischaemia was also studied separately. In all control rats, the immunoexpression of TLR 2 and TLR 4 was not detected. However, the expression of both TLRs was evident in all brains injured by HI or exposed to alpha-toxin. The immunoexpression was localised in the wall of the small brain vessels, cells of ependyma and leptomeninges. In such vessels the spectrum of ultrastructural lesions was found. The presence of TLR4 detected in the nerve cells of the subcortical gray matter of the brain is particularly of interest, but requires further studies. The presence of TLR 4 antigen in the nerve cells of the subcortical gray matter is particularly of interest. In conclusion, the results show that brain microvessels through TLRs may participate in the immune response of brain affected by bacterial infection as well as injured by non-infection insults.

Effects of ischaemia and hypoxia on the development of the nervous system in acardiac foetus.

The twin-reversed arterial perfusion (TRAP) sequence and development of an acardius are rare and severe complications in monozygotic twin pregnancy. Haemodynamic disturbances in placental perfusion via abnormal vascular anastomoses allow inter-twin transfusion to occur. Because of blood perfusion, one of the twins is poorly oxygenated and contains metabolic waste products. Retrograde placental perfusion leads to the formation of a non-viable malformed acardiac foetus. We studied the effects of haemodynamic disturbances in acardiac foetus on the development of the nervous system. The acardius was a product of a 32-weeks pregnancy. Caesarean section yielded a skin covered ovoid mass (size, 10 x 8 cm; weight, 220 g). The dissection of the acardiac twin showed a skin with hair and appendages, rudimentary lower limbs, vertebral column and brain mass. The rudimentary brain tissue was considerably disorganised structurally. We distinguished two main morphological forms of various appearances. In the centre, we observed a scarcely vascularised mass of tissue containing mature and immature neurones, glial cells and randomly distributed fibres. The mass of tissue appeared poorly differentiated, although there were some arrangements reminiscent of cerebral structures. Clusters of neurones provided a slight suggestion of nuclear or fibre structure. The cerebellar cortex was the only well recognisable structure. In the other fragment of the tissue, we found a slit cavity with ependymal outline and well-developed choroid plexus, which seemed to represent the 3rd ventricle. The scarcely vascularised disorganised tissue was surrounded by the highly vascularised one. It included many thin-walled sinusoid vessels. In some places, they were so concentrated that they resembled cavernous haemangioma. The spinal cord appeared comparatively well organised with a slightly dilated central canal. The morphological picture of the rudimentary brain tissue was similar to the picture of the cerebrovasculosa area. The effect of ischaemia in the presented case is the anomalous formation of the cerebral structures. The morphological features imply that the failure occurred after neurulation and before the prosencephalic began to grow. The failure of neural tube formation occurred on the 22nd-25th day of gestation. The malformed formation of the nervous system might be caused by impaired induction due to altered gene expression or to the interference of exogenous agents that interrupt normal development. The haemodynamic abnormal placental circulation, which induced lack of oxygen supply and nutritional deficiency, implies the morphological pattern of the anomaly.

[Apoptosis: physiological cell death and its role in pathogenesis of diseases]. / Apoptoza--fizjologiczna smierc komórki oraz jej udzial w patogenezie chorób.

Apoptosis is a physiological process of cell death by which a single cell may be eliminated from the living tissue. Since the process is mediated by specific proteins encoded in the host's genome, it is also a programmed cell death. Apoptosis is responsible for tissue remodelling during the development and turnover of normal tissue (e.g. haematopoietic cells) throughout the life span of multicellular organisms. In contrast to cells undergoing a pathological cell death (necrosis), the morphological changes that accompany apoptosis are characterised by condensation of chromatin and cytoplasm and subsequent fragmentation of the cell into small membrane-bound segments called apoptotic bodies. The maintenance of membrane integrity in apoptosis prevents the release of deleterious cytoplasmic substances and the activation of inflammatory responses. Apoptosis can be initiated by a variety of events arising either within the cell (p53) or externally (death receptor ligands engaging specific cell surface receptors of the target cell). Following recognition of the stimuli and clustering of membrane proteins into a death domain, certain cytoplasmic proenzymes are converted to their active form (caspases). After the death effector machinery is activated, the cell enters the irreversible common degradation phase of cytoskeletal disorganisation. Survival proteins (bcl-2 family) control the caspase-driven engine of destruction. Disordered apoptotic process participates in the pathogenesis of various diseases, such as neoplasms, chronic inflammatory or systemic autoimmune diseases, and other conditions.

Morphology of pineal glands in human foetuses and infants with brain lesions.

The pineal gland is an organ involved in regulation of homeostasis and body rhythms. It plays an important role in the growth foetuses and adaptation of newborns to new environmental conditions. The requirements of foetuses and newborns progressively change during development. The purpose of the study was to evaluate morphological changes of pineal glands in foetuses and infants with brain lesions. The results of our study showed that parenchyma of developing pineal glands was susceptible to injury in most autopsied foetal and infantile cases. Morphological changes in pineal glands were found in 90% of autopsied brains but 100% of the cases had infections. The lesions in the pineal included mainly haemorrhagic, necrotic and cystic changes. In our autopsied foetuses and children, morphological changes in pineal glands were concomitant with various lesions of brain parenchyma. All results of our study lead to the conclusion that the pineal gland during its development is very susceptible to injury. The failure of normal pineal gland development and subsequent impaired production of melatonin decrease resistance of newborns and children to various environmental harmful agents.

Proinflammatory cytokines in injured rat brain following perinatal asphyxia.

In contrast to astrogliosis, which is common to injuries of the adult CNS, in the developing brain this process is minimal. Reasons postulated for this include the relative immaturity of the immune system and the consequent insufficient production of cytokines to evoke astrogliosis. To explore this hypothesis, the study was undertaken to detect the presence of some proinflammatory cytokines in the injured rat brain following perinatal asphyxia (ischaemia/hypoxia). The localisation of TNF-alpha, IL-15, IL-17 and IL-17 receptors was visualised by means of immunohistochemistry. In numerous neurones of the rat brain, the IL-17 appeared to be constitutively expressed. In the early period of inflammation the IL-15 was produced mainly by the blood cells penetrating the injured brain but later it was synthesised also by reactive astrocytes surrounding brain cysts and forming dense astrogliosis around necrotic brain regions. The direct effect on astrogliosis of other estimated cytokines seems to be negligible. All the results lead to the conclusion that from all cytokines identified in the injured immature rat brain the IL-15 plays the most important role during inflammatory response and participates in the gliosis of reactive astrocytes.

Discrete glioneuronal malformative lesions in the foetal and infantile cerebral cortex.

Microdysgenesis is a term describing microscopic cortical cytoarchitectural abnormalities. Histologically this change shows an irregular glioneuronal tissue combination forming an abnormal structure of the cortex. The pathological features of this malformation are subtle and less well defined than other more distinctive cortical malformations. The clinical significance of these discrete glioneuronal malformations is controversial. Microscopic dysgenetic changes have been reported in cases with intractable epilepsy but similar changes may be seen in neurologically normal adults. The purpose of our study was the investigation of microdysgenetic lesions in the developing nervous system with regard to normal neuronal migration, differentiation and maturation. The post-mortem routine investigated foetal and infantile brains which were analysed histologically for the presence of discrete cortical malformations. A wide spectrum of cytoarchitectural glioneuronal malformations was found in the investigated material. We observed leptomeningeal glioneuronal heterotopias, subpial bands of heterotopic neurones, nests of ectopic neurones in the first cortical layer, neuronal and glial clusters, small foci with irregularity of laminar structure of the cortex. Microdysgenetic changes arose from an insult occurring in the later stages of cortical development and influencing the normal fate of neuroglial cells. Various types of focal morphological and cytoarchitectonial developmental abnormalities have been associated with behavioural and neuropsychological deficits in older infants.