Blood-brain barrier ultrastructural alterations in human congenital hydrocephalus and Arnold-Chiari malformation.

Cortical biopsies of 13 patients with clinical diagnosis of congenital hydrocephalus, Arnold-Chiari malformation and hydrocephalus, and postmeningitis hydrocephalus were examined by transmission electron microscopy to study the damage of endothelial cells, basement membrane, astrocytic end-feet layer, and perivascular space. Capillaries from the parietal and frontal cortex showed increased vesicular and vacuolar transport, intact endothelial junctions, thin and immature basement membrane, swollen perivascular astrocytic end-feet layer, and enlarged perivascular space. In areas of severe oedema, open endothelial junctions, swollen basement membrane, absent perivascular astrocytic end-feet layer, enlarged perivascular space, and disrupted perivascular neuropil were observed. The electron microscopic findings demonstrated breakdown of the blood-brain barrier in all cases examined.

Nerve cell nuclear and nucleolar abnormalities in the human oedematous cerebral cortex. An electron microscopic study using cortical biopsies.

Cerebral cortical biopsies of 17 patients with clinical diagnosis of congenital hydrocephalus, complicated brain trauma, cerebellar syndrome and vascular anomaly were examined with the transmission electron microscope to study the nuclear and nucleolar abnormalities induced by moderate and severe brain oedema, and the associated anoxic-ischemic conditions of brain tissue. In infant patients with congenital hydrocephalus and Arnold-Chiari malformation two different structural patterns of immature chromatin organization were found: the clear type characterized by a clear granular and fibrillar structure of euchromatin, scarce heterochromatin masses and few perichromatin granules, and a dense granular and fibrillar euchromatin with abundant and scattered heterochromatin masses, and increased number of perichromatin granules. The lobulated nuclei exhibited an irregularly dilated and fragmented perinuclear cistern, and areas of apparently intact nuclear pore complexes alternating with regions of nuclear pore complex disassembly. In moderate traumatic brain injuries some nucleoli exhibit apparent intact nucleolar substructures, and in severe brain oedema some nucleoli appeared shrunken and irregularly outlined with one or two fibrillar centers, and others were disintegrated. The nuclear and nucleolar morphological alterations are discussed in relation with oxidative stress, peroxidative damage, hemoglobin-induced cytotoxicity, calcium overload, glutamate excitotoxicity, and caspase activation.

Lysosome abnormalities and lipofucsin content of nerve cells of oedematous human cerebral cortex.

Lysosome alterations and lipofucsin content of nerve cells, capillary endothelial cells and pericytes were examined in the anoxic-ischaemic brain parenchyma of thirty two patients with congenital hydrocephalus, complicated brain traumatic injuries, brain tumours and vascular anomalies. Cortical biopsies of frontal, parietal and temporal cortex were processed for transmission electron microscopy. In oedematous non pyramidal and pyramidal nerve cells, lysosomes showed fragmentation of their limiting membranes and an associated dense granulation. Areas of cytoplasmic focal necrosis were observed surrounding the lysosomes. Lipofucsin granules were also observed in neonate and infant patients with congenital hydrocephalus, suggesting that lipofucsin formation is a life span process. Lysosomes coexisting with an increased amount of lipofucsin granules were observed in young and adult patients with brain trauma, tumours and vascular anomalies. Phagocytic astrocytes and activated oligodendroglial cells showed the overall spectrum of an altered endosomal/lysosomal system. Lipofucsin granules and multivesicular bodies also were distinguished in endothelial and pericyte cells. The role of released and activated lysosomal enzymes is discussed in relation with the cytoplasmatic focal necrosis of nerve cells and the genesis of moderate and severe oedema.

The Chiari II malformation: cause and impact.

INTRODUCTION: It is the Chiari II malformation and its effects that determine the quality of life of the individual born with spina bifida. DISCUSSION: The cause of this malformation has been a source of debate for many years. Understanding the cause enables strategies for the management of problems created by this malformation to be developed. An open neural tube defect allows fluid to escape from the cranial vesicles, altering the intracranial environment and leads to all of the brain changes seen in the Chiari II malformation. Decompression of the intracranial vesicles causes overcrowding, decrease in the size of the third ventricle, and changes in the fetal skull. It also permanently links the intracranial ventricular system to the spinal cord central canal.

Morphological changes of dendrites in the human edematous cerebral cortex. A transmission electron microscopic study.

The structural pathology of dendritic processes has been examined in 38 patients with clinical diagnosis of brain trauma, brain tumours and congenital malformations. Cortical biopsies of frontal, parietal, temporal and occipital cortex were conventionally processed for transmission electron microscopy. Isolated ultrathin sections and montages of electron micrographs were used to trace the intracortical dendritic course. Swollen and beaded dendrites were observed in all cases examined, which exhibited fragmentation of limiting plasma membrane and cytoskeletal structures. The swollen dendrites showed vacuolization, dense residual bodies, enlarged rough and smooth endoplasmic reticulum, edematous clear and dark mitochondria, a decreased synaptic density of shaft synapses, edematous and dystrophic changes of spine apparatus and a partial loss of dendritic spines. A wide variety of dendritic spine shapes were observed: mushroom-type, stubby, gem-like filiform spine, and megaspine, considered as spine dysgenesis in the congenital malformations and spine pathology and spine plasticity in brain traumatic injuries and brain tumours. The multifactorial processes associated with brain edema and brain ischemia, such as calcium overload, activation of calcium-dependent proteolytic enzymes, protein aggregation, glutamate-induced neurotoxicity, release of lysosomal enzymes, deficit of ATP, stress oxidative and lipid peroxidation have been considered in relation with the pathological dendritic changes. Dendrotoxicity due to brain edema and brain ischemia seems to be the fundamental pathogenetic mechanism.