Pathology of mitochondria in MELAS syndrome: an ultrastructural study.

Ultrastructural changes in skeletal muscle biopsy in a 24-year-old female patient with clinically suspected mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes (MELAS) syndrome are presented. We observed proliferation and/or pleomorphism of mitochondria in skeletal muscle and smooth muscle cells of arterioles, as well as in pericytes of capillaries. Paracrystalline inclusions were found only in damaged mitochondria of skeletal muscle. Genetic testing revealed a point mutation in A3243G tRNALeu(UUR) typical for MELAS syndrome. We conclude that differentiated pathological changes of mitochondria in the studied types of cells may be associated with the different energy requirements of these cells.

Novel mutation of the NOTCH3 gene in a Polish family with CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small blood vessels disease caused by mutations in the gene encoding the neurogenic locus notch homolog protein 3 (NOTCH 3). We present a Polish family with a previously unreported novel mutation in exon 12 c.1851C>C/G of the NOTCH3 gene and varying disease expression. One of the two family members with the confirmed mutation presented with all the main CADASIL symptoms; while, his affected father was nearly asymptomatic. Both family members had epilepsy, coronary artery disease, and abdominal aorta aneurysm. Our observation confirms there is phenotypic variability in CADASIL not only between, but also within, families carrying the same mutation.

Morphological changes of skeletal muscle in spinal and bulbar muscular atrophy (SBMA), Kennedy's disease: a case report.

Spinal and bulbar muscular atrophy (SBMA, Kennedy's disease) is an X-linked recessive disease affecting lower motor neurons. In the present case report, we describe morphological changes in a muscle biopsy obtained from a 62-year-old patient with gynecomastia and with the following neurological symptoms: dysphagia, dysarthria, wasting and fasciculation of the tongue, proximal weakness, fasciculations in the limb muscles, and an absence of all tendon reflexes. Neurogenic alternations were predominantly observed using light and electron microscopy. The angulated atrophic muscle fibers formed bundles. The numerous nuclei were pyknotic or pale, some of them were also ubiquitin positive; they were grouped inside so-called "nuclear sacks". At the ultrastructural level, atrophic muscle fibers revealed disruption and loss of sarcomeres, duplication of Z-line, and rod-like structures. The nuclei, often with irregular shapes, revealed varying degrees of chromatin condensation, from dispersed to highly condensed, like pyknotic nuclei. Occasionally electron-dense inclusions in the nuclei were found. Some myogenic features like hypertrophic muscle fibers and proliferation of connective tissue were also visible. The neurogenic and myogenic pathological changes suggested SBMA, which was confirmed with genetic analysis (trinucleotide CAG (glutamie)-repeat expansion in the androgen-receptor gene).

Pericytes as a new target for pathological processes in CADASIL.

CADASIL is a generalized angiopathy caused by mutations in NOTCH 3 gene leading to degeneration and loss of vascular smooth muscle cells (VSMC) in small arteries and arterioles. Since the receptor protein encoded by NOTCH 3 gene is expressed not only on VSMC but also on pericytes, pericytes and capillary vessels can be damaged by CADASIL. To check this hypothesis we examined microvessels in autopsy brains and skin-muscle biopsies of CADASIL patients. We found degeneration and loss of pericytes in capillary vessels. Pericytes were shrunken and their cytoplasm contained numerous vacuoles, big vesicular structures and complexes of enlarged pathological mitochondria. Degenerative changes were also observed within endothelial-pericytic connections, especially within peg-and-socket junctions. Nearby pericyte cell membranes or inside infoldings, deposits of granular osmiophilic material (GOM) were usually seen. In the affected capillaries endothelial cells revealed features of degeneration, selective death or swelling, leading to narrowing or occlusion of the capillary lumen. Our findings indicate that in CADASIL not only VSMC but also pericytes are severely damaged. Pericyte involvement in CADASIL can result in increased permeability of capillary vessels and disturbances in cerebral microcirculation, leading to white matter injury. Since in capillaries pericytes regulate vessel contractility, their degeneration can also cause defective vasomotor reactivity, the phenomenon observed very early in CADASIL, before development of histopathological changes in vessel walls.

The spectrum of microvascular ultrastructural changes in the subpopulation of patients with migraine and cerebral white matter hyperintensities on MRI.

INTRODUCTION: Migraine is considered not only as a separate clinical entity but also as a symptom of various brain disorders, including cerebral small vessel diseases. Since cerebral small vessel diseases are usually general angiopathies, evaluation of biopsy material other than brain tissue may help in their diagnosis in vivo. In patients with migraine, brain magnetic resonance imaging (MRI) often shows hyperintense changes in the cerebral white matter. Such changes may indicate the symptomatic nature of migraine and coexisting structural or biochemical vascular abnormalities. MATERIAL AND METHODS: To verify the hypothesis of the symptomatic nature of migraine in patients with abnormal brain neuroimaging, we performed an ultrastructural examination of skin and skeletal muscle vessels in biopsy material from 40 patients with clinically diagnosed migraine and hyperintense white matter lesions on MRI. RESULTS: In 80% of the examined patients, ultrastructural examination showed various pathological changes in the microvessels including abnormalities characteristic of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and elastin disorders, as well as less specific changes such as thickening of the basal lamina, narrowing of the vessel lumen, degeneration of the vessel wall cells, endothelial activation, oncosis-like changes, and the presence of various types of deposits in the vessel wall. In 20% of the examined cases, ultrastructural examination of the vessels was normal. CONCLUSIONS: Patients with migraine and hyperintense cerebral white matter changes on MRI have an increased risk of concomitant microangiopathy. In this group of patients, skin-muscle biopsy allows the identification of cases with coexisting vessel abnormalities.

Morphological and ultrastructural changes in Herpes simplex encephalomyelitis: an attempt to determinate the etiological factor.

Herpes simplex encephalomyelitis (HSE) is a rare disease with a high mortality rate. Correct diagnosis is established on the basis of the combination of the clinical and investigative features. Unfortunately, precise diagnosis remains difficult due to several clinical similarities and false negative or inconclusive results of diagnostic tests. Here, we present two cases of HSE together with the morphological and ultrastructural picture. The first case was a 45-year-old man with acute symptoms of encephalitis, and the other one was a 28-year-old woman presenting subacute encephalomyelitis. Both cases had negative serologic and molecular results for Herpes simplex in the blood and cerebrospinal fluid. Brain and spinal cord samples taken from both cases were stained typically with histological and immunohistochemical methods and small tissue fragments were examined with the transmission electron microscope (TEM). Microscopic examination confirmed viral encephalomyelitis in both cases. An electron micrograph showed typical intranuclear viral particles inside of damaged neurons, which together with topography of brain and spinal cord changes suggest HHV-1/HHV-2 in the first case and/or HHV-3 in the other case. Thus, morphological and ultrastructural examinations may be a useful tool to set up correct diagnosis and help to determine the pathogenic factor in patients suspected of viral encephalomyelitis.

Kufs' disease: diagnostic difficulties in the examination of extracerebral biopsies.

Kufs' disease or NCL4 (neuronal ceroid lipofuscinosis type 4) is a rare and poorly characterized, adult-onset form of NCL. The mutation in gene CLN, underlying Kufs' disease, still remains unknown. The diagnosis of this disease is difficult because it is based only on clinical and ultrastructural examinations. We report the case of a 45-year-old woman referred to the Neurological Department with suspicion of Creutzfeldt-Jakob disease (CJD). CJD as well as infectious, autoimmune and some lysosomal diseases were excluded. Since clinical symptoms, i.e. psychotic, auditory and visual hallucinations as well as behavioural disturbances, still suggested metabolic or neurodegenerative disease, a skin and muscle biopsy was performed. On ultrastructural examination the muscle biopsy revealed the subsarcolemmal accumulation of lipofuscin, lipofuscin-like and granular osmiophilic deposits (GRODs). The most unique fingerprint deposits (FP) and curvilinear profiles (CP) for diagnosis of Kufs' disease were located in vascular smooth muscle cells (VSMCs). In these cells lipofuscin-like deposits and GRODs were also visible. The fact that FP and CP were found exclusively in VSMCs jointly with clinical and laboratory data allows us to diagnose Kufs' disease in our patient.

Immunohistochemical and ultrastructural changes in the brain in probable adult glycogenosis type IV: adult polyglucosan body disease.

Glycogenosis type IV is caused by a deficiency of glycogen branching enzyme (alpha-1,4 glucan 6-transglucosylase). Adult polyglucosan body disease (APBD) may represent a neuropathological hallmark of the adult form of this storage disease of the central nervous system. We analysed a case of a 45-year-old unconscious woman who died three days after admission to the hospital. Neuropathological examination revealed massive accumulation of polyglucosan bodies (PBs) in the cortex and white matter of the whole brain. PBs were located in the processes of neurons, astrocytes and microglial cells. The storage material in the cytoplasm of neurons and glial cells was visible as fine granules. Ultrastructurally, PBs consisted of non-membrane-bound deposits of branched and densely packed filaments, measuring about 7-10 nm in diameter, typical of polyglucosan bodies. APBD patients develop upper and lower neuron disease and dementia, probably secondary to the disruption of neuron and astrocyte functions.

Amyloid angiopathy in idiopathic Parkinson's disease. Immunohistochemical and ultrastructural study.

The prevalence of cerebral amyloid angiopathy (CAA) and its association with intellectual decline in idiopathic Parkinson's disease (iPD) remain unclear. To identify the role of CAA in iPD dementia the prevalence and severity of CAA were investigated, with particular respect to changes in vessel wall structure. Twenty-eight autopsy Parkinsonian brains and fourteen age-matched controls, post-mortem revised histopathologically for the presence of alpha-synuclein and Alzheimer's disease (AD)-type pathology, using standardized clinico-neuropathological criteria, underwent further investigation. Histological, immunohistochemical staining methods with antibodies to amyloid beta-peptide, alpha-actin, collagen III, collagen IV and CD34 as well as ultrastructural methods were used. The findings showed that the prevalence of CAA in the iPD cohort was higher (53%) than in controls (28%). CAA occurred more frequently in the iPD+AD (70%) sub-set than in the iPD-AD (44%) one. The progression of CAA was differentiated, with predominance of mild stage. Diminished smooth muscle actin and collagen IV expression in the vascular media with concomitant collagen III positive immunoreactivity in the intima were observed only in very severe CAA. Ultrastructural assay revealed degenerative changes in vessel smooth muscle cells and thickening of their basement membrane with the focal accumulation of amyloid fibres and fibrillar collagen in both iPD -AD and iPD+AD cases, but the most severe CAA-type changes were visible in the iPD+AD sub-set. The same type of immunoreactivity (Abeta42 positive and Abeta40 positive) of arterial CAA and parenchymal neuritic plaques, as well as capillary CAA and diffuse plaques (Abeta42 positive and Abeta40 negative), may indicate pathogenic similarities and differences between both types of degenerative changes on the one hand and time-different changes or local different processing of amyloid precursor protein on the other.

Granular cell astrocytoma. A case report with immunohistochemical and ultrastructural characterization.

Granular cell astrocytoma (GCA) is an uncommon type of granular cell tumours (GCTs) in the central nervous system. Granular cells in these tumours are of enigmatic origin. We report a case of cerebral GCA in a 59-year-old man who suffered from diabetes and Addison-Biermer disease. The tumour was localized in the left parietal lobe. Microscopically, the tumour was almost entirely composed of large, polygonal cells with round to oval, granular eosinophilic, PAS-positive cytoplasm. The nuclei were located centrally or eccentrically and sometimes exhibited nucleolar vacuoles. The tumour cells were arranged in nests surrounded by blood vessels and connective tissue. Immunohistochemically, the granular tumour cells were reactive for GFAP and vimentin. They were intensively stained for ubiquitin and some of them were reactive for CD68. Moreover, a lot of stromal cells expressed CD68 reactivity. Ultrastructurally, most tumour cells were round or oval with only a few or without filaments. Their cytoplasm was filled with electron-dense granular material limited by a single membrane and autophagic vacuoles. Another type of tumour cells, present in a significantly lower number, revealed abundant cytoplasm with numerous intermediate filaments, swollen rough endoplasmic reticulum, mitochondria and a few clusters of granular material. Cells with numerous condensed electron-dense, bizarrely-shaped mitochondria and few filaments were occasionally observed. Among granular cells, macrophages with vacuoles and/or lamellar structures were visible. In our case, both immunohistochemical and ultrastructural analysis supported astroglial origin of the granular cell tumour.

Pathology of skeletal muscle cells in adult-onset glycogenosis type II (Pompe disease): ultrastructural study.

Ultrastructural analysis of the skeletal muscle in adult-onset Pompe disease revealed lysosomal and cytoplasmic glycogen storage, autophagic vacuoles and abnormal mitochondria. Significant glycogen accumulation within lysosomes causes their rupture and release of glycogen into the cytoplasm. Excess cytoplasmic glycogen could lead to damage of the structure of muscle cells including myofibrils. In consequence, parts of the sarcoplasm and damaged organelles were sequestered within membrane-limited vacuoles. We suppose that massive accumulation of autophagic vacuoles results from the inability of destroyed lysosomes to fuse with vacuoles. Autophagic vacuoles may be a prominent feature of muscle cells in adult glycogenosis type II.

Clinical, biochemical, neuropathological and molecular findings of the first Polish case of adenylosuccinase deficiency.

Adenylosuccinase (ADSL) deficiency is an autosomal recessive disorder affecting mainly the nervous system. The disease causes psychomotor retardation, frequently with autistic features and epilepsy. ADSL deficiency may be diagnosed by detection of two abnormal metabolites in body fluids--succinyladenosine (S-Ado) and succinylaminoimidazole carboxamide riboside (SAICAr). It is assumed that the former metabolite is neurotoxic. We present clinical, biochemical and neuropathological findings of a child affected by a severe form of ADSL deficiency. She had progressive neurological symptoms that started immediately after birth and died at 2.5 months of age. Macroscopically the brain showed signs of moderate atrophy. Histological examination of all grey matter structures showed widespread damage of neurons accompanied by microspongiosis of neuropile. Cerebral white matter showed lack of myelination in the centrum semiovale and diffuse spongiosis of neuropile. Myelination appropriate for the age was visible in posterior limb of internal capsule, in striatum, thalamus and in brain stem structures but diffuse destruction of myelin sheets was seen with severe marked astroglial reaction with signs of destruction of the cells and their processes. Ultrastructural examination showed enormous destruction of all cellular elements, but astonishingly mitochondria were relatively spared. The neuropathological changes can be considered as the neurotoxic result of metabolic disturbances connected with adenylosuccinase deficiency.

Giant cell ependymoma of the spinal cord and fourth ventricle coexisting with syringomyelia.

This report presents a case of widespread intramedullary giant cell ependymoma arising from the central canal of the C4 segment of the spinal cord in a 28-year-old man admitted to hospital with tetraplegia and signs of increased intracranial pressure, eight months after surgical spinal cervical decompression without tetraplegia improvement. Magnetic resonance imaging and autopsy revealed a tumour extending from segment C3/C4 of the spinal cord to the lower half of the fourth ventricle with coexisting syringomyelia. This slow-growing ependymoma of low-grade malignancy exhibited unusual morphology as well as degenerative and ischaemic changes. All intramedullary and ventricular tumour segments featured coexistence of two forms of neoplastic cell, classic ependymomal and pleomorphic multinucleated giant cells. The morphological diagnostic criteria of unusual giant-cell variant of ependymoma and tumour-related syringomyelia in adults are discussed, based on the presented case and a review of the literature.

Adult glycogenosis type II (Pompe's disease): morphological abnormalities in muscle and skin biopsies compared with acid alpha-glucosidase activity.

Glycogen storage disease type II (GSD II) is an autosomal recessive deficiency of acidalpha-1,4-glucosidase(GAA) caused by mutations in the GAA gene located on human chromosome 17 (17q 25.2-q 25.3). Although its pathophysiology is partially understood, it has not yet been elucidated whether the level of GAA deficiency is directly proportional to the level of glycogen storage, vacuolar degeneration and/or GSD II severity. Muscle and skin biopsies were taken from three female patients with symptoms of progressive muscle weakness and respiratory failure: patient 1 aged 19, as well as patients 2 and 3 (two sisters) aged 31 and 29, respectively. Initial clinical manifestations, respiratory failure and muscle weakness, were similar in all the examined patients, while their character and intensity differed. For each examined patient, the activity of lysosomal GAA (at pH 3.8) was measured fluorometrically in isolated blood leukocytes (L) and dried blood spots (DBS). Biopsy samples were studied histologically, immunohistologically and ultrastructurally. Each of them displayed similar morphological features, although with different intensity. Muscle fibres were irregular in size with smaller non-rounded fibres and vacuolar degeneration. Invacuoles,we observed glycogen and intense positive ubiquitin reaction. Myofibrils were almost completely destroyed by the accumulation of glycogen granules in lysosomes and those free, without limiting membranes as well as by vacuoles of various size. Autophagic vacuoles were visible occasionally. Excess glycogen was also present in the walls of muscle and skin capillaries. All three patients showed reduced GAA activity ratios measured at pH 3.8 with and without acarbose (patient 1 - 0.12 in DBS and 0.07 in L; patient 2 - 0.05 in DBS and 0.07 in L; and patient 3 - 0.12 in DBS and 0.09 in L). Based on the study results, we concluded that GAA deficiency in vitro in late-onset type II glycogenosis was not directly proportional to the amount of glycogen storage, vacuolar degeneration and disease severity.

Small cerebral vessel disease in familial amyloid and non-amyloid angiopathies: FAD-PS-1 (P117L) mutation and CADASIL. Immunohistochemical and ultrastructural studies.

Three patients (of two unrelated Polish families) with early-adult onset dementia were subjects of the study. Two cases, previously diagnosed as familial Alzheimer's disease (FAD) with cerebral amyloid angiopathy (CAA), were confirmed by genetic and neuropathological studies, and one case of CADASIL was ultrastructurally confirmed by the presence of vascular granular osmiophilic material. Now the brain autopsy material has been reinvestigated using immunohistochemical (IHC) markers for vascular smooth muscle cells, paying special attention to collagen markers for extracellular matrix components and ultrastructural microvascular changes. In both diseases, IHC examination showed a reduction or loss of expression of smooth muscle actin (SMA) in tunica media of the cerebral arterioles. Fibrous thickening of the wall of the small meningeal arteries, intracerebral arterioles and numerous capillaries, with amyloid or granular deposits, drew our attention. In these vessels, marked expression of fibrillar collagen type III as well as strong immunoreactivity of the basement membrane (BM) component collagen type IV were found. The most damage was observed in the FAD/CAA double-barrel vessel wall and in some CADASIL arterioles changed by fibrinoid necrosis. The fibrous changes of the small vessels were more distinct in CADASIL t han in FAD/CAA. In FAD,electronmicroscopic examination revealed both amyloid and collagen fibres within the thickened BM of capillaries and the small arterioles. Clusters of collagen fibres between lamellae of BM, frequently in a pericyte position,were observed,and some were seen in the degenerated pericytes as well. Typical changes of the pericytes were accumulation of lipofuscin-like material and their degeneration. The mitochondria of the pericytes and of the endothelium were rare and swollen, with damaged and reduced cristae. The VSMCs of the arteriolar walls exhibited degenerative changes with atrophy of the cellular organelles. The fibrous,collagen-richCADASILsmallcerebralvessels,despite the weakness of the vessel wall due to reduction of VSMCs, appeared to be stronger than in FAD/CAA. These findings may suggest an accelerated process of transformation of the small cerebral vessels in which early onset of VSMCs loss is a predominant feature of the vascular changes in both presented diseases.

Intracerebral hemorrhage in the context of cerebral amyloid angiopathy and varied time of onset of cerebral venous thrombosis: a case report.

In patients with cerebral venous thrombosis (CVT) the incidence of intracerebral hemorrhage (ICH) is estimated at about 37% and subarachnoid hemorrhage (SAH) at 1% of patients. A case with coincident occurrence of ICH, SAH and CVT in a patient with cerebral amyloid angiopathy (CAA) is reported. A 79-year-old woman was admitted to the Neurological Department after the occurrence of generalized seizures, the first in her life. On admission she was unconscious with right hemiparesis and deviation of eyes to the left. On computed tomography (CT) scan many hemorrhagic infarcts were present in the frontal, parietal, temporal and left occipital lobes. Angio-CT revealed thrombosis in the right transverse sinus, right internal carotid vein and superior sagittal sinus. Her state slowly deteriorated. She died after 6 days. Neuropathologically, many hemorrhagic infarcts were observed in cortical regions in the vicinity of veins with thrombosis and in the white matter. The varied time of onset of thrombosis of the right sigmoid sinus, right superior petrosal sinus, superior sagittal sinus, right transverse sinus and the proximal part of the right internal carotid vein was confirmed. cerebral amyloid angiopathy in brain vessels was diagnosed. Subarachnoid hemorrhage is a very uncommon presentation of CVT and may coexist with CAA. We can only speculate that CAA may have an effect on vein destruction and can promote cerebral vein thrombosis and in consequence also predispose to intracerebral hemorrhage and subarachnoid hemorrhage. The most probable cause of extensive thrombosis was a coagulation disorder.

Ultrastructural picture of blood vessels in muscle and skin biopsy in CADASIL.

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy) is an inherited systemic vascular disorder affecting mainly the central nervous system. We performed detailed ultrastructural examination of the small vessels in the skin and skeletal muscle of a 51-year-old patient with bilateral cerebral white matter lesions, who had a history of two ischaemic strokes. The arterioles were characterized by degeneration and loss of vascular smooth muscle cells (VSMCs). GOM deposits, varied in size and shape, were located in the neighbourhood of the smooth muscle cells, often within an infolding of the cell membrane. No apparent correlations between presence, size or number of GOM deposits and damage severity of vascular smooth muscle cells were seen. Moreover, in some capillaries there were GOM deposits which were seen in the basement membrane near pericytes and endothelial cells. On the other hand, lesions of VMSCs and/or endothelial cells were also visible on the sections of blood vessels devoid of GOM deposits. Genetic tests detected a mutation in exon 4 of the Notch3 gene. It confirmed the initial diagnosis which had been suggested on the basis of the clinical and MRI findings.

The brain immune response in human prion diseases. Microglial activation and microglial disease. I. Sporadic Creutzfeldt-Jakob disease.

A study of microglial activation and its contribution to the CNS immune response was performed on the brain autopsy material of 40 patients with definite sporadic Creutzfeldt-Jakob disease (sCJD). Spatial patterns of microglial activation and prion protein disease-associated (PrPd) deposition were compared in cerebellar and cerebral cortices using immunohistochemical (IHC) activation markers. Morphological phenotype forms of microglial cells in activation stages were assessed immunohistochemically (IHC). The immune inflammatory response dominated by microglia was found to be a characteristic feature in CJD. Differences in the intensity and patterns of microglial activation corresponded to variable patterns of PrP deposition, whereas the morphological phenotype forms of microglia were specific for activation stages. The presence of activated microglial cells in the various activation stages regardless of illness duration indicates continuous microglial activity and microglial contribution to the spread of infection for the whole symptomatic period of the disease. Remarkable vacuolar degeneration changes of numerous microglial cells in different activation stages including homing stage may suggest dysfunction of microglial immune surveillance in human sCJD that can significantly contribute to transmissible spongiform encephalopathy (TSE) pathogenesis.

Co-existing spinal canal tumours and CADASIL - a diagnostic challenge.

We would like to present a case of a 51-year-old patient with two rare co-existing diseases. The patient was suffering from two tumours in the lumbar region of the spinal canal, which caused development of hydrocephalus. Diffuse white matter hyperintensities (WMH) were observed in our patient's brain imaging. She was also suffering from headaches and she had two mild strokes. We performed some further diagnostic procedures and found out that the patient was suffering from CADASIL. CADASIL was confirmed by both ultrastructural analysis and genetic testing.

Quantitative analysis of activated microglia, ramified and damage of processes in the frontal and temporal lobes of chronic schizophrenics.

Under pathological conditions, microglial cells undergo activation, which is manifested by the expression of histocompatibility locus antigens class II (HLA II) on their surface as well as by proliferation and varied morphological forms. In schizophrenia, characterised by an essential role played by immunological mechanisms, quantitative analysis of activated microglia -- with well-developed ramification (RM), degenerative traits and damaged processes (from their shortening to their complete lack) (DM) -- may contribute to better understanding of schizophrenia etiopathogenesis. Quantitative analysis was performed on slices derived from the frontal and temporal lobes of 9 brains of schizophrenics and 6 control brains. The nonparametric Mann-Whitney U test was used to assess quantitative differences in the distribution of microglia in these regions of the brain. Statistical analyses were performed with STATISTICA 6.5 Programme. In both structures of the brain, the number of activated microglial cells was higher in schizophrenic brains than in control brains. Except for the first layer of the cerebral cortex with the same amounts of RM and DM, the number of DM cells in the remaining regions was several-fold higher than that of RM cells. It is most likely that disturbances in calcium metabolism and energetic balance as well as antibodies produced in the course of schizophrenia are the agents able to trigger a cascade transforming RM into DM. Quantitative differences in RM and DM, observed between the studied structures and cortical regions, could depend not only on functioning of inter-neuronal and inter-structural links. Our study suggests a pivotal role of microglial cells in repair processes and/or etiopathogenesis of schizophrenia and indicates that they undergo substantial damage in the course of chronic schizophrenia.