There is increasing evidence that so-called "autophagic cell death" participates in cell degeneration in certain pathological conditions. Autophagy might be involved in some neurodegenerative processes, including lateral amyotrophic sclerosis (SLA). The exact mechanism leading to progressive motor neuron (MN) loss remains unclear, but glutamate-mediated mechanism is thought to be responsible. Previous ultrastructural studies by the authors performed on a model of SLA in vitro, based on chronic glutamate excitotoxicity, revealed a subset of morphological features characteristic to different modes of neuronal death, including autophagic degeneration. The contribution of this pathway of MNs death is evaluated in organotypic cultures of rat lumbar spinal cord chronically exposed to specific glutamate uptake blockers: DL-threo-beta-hydroxyaspartate (THA) and L-transpyrrolidine-2,4-dicarboxylate (PDC). The study documents the various steps of authophagy in slowly evolving process of MN neurodegeneration. The cells undergoing autophagy usually exhibited sequestration of some parts of cytoplasm with normal and/or degenerated organelles, whereas other parts of cytoplasm as well as neuronal nucleus remained unchanged. The advanced autophagic changes were often associated with other modes of MN death, especially with apoptosis. Numerous MNs revealed apoptotic nuclear features with typical peripheral margination of nuclear chromatin, accompanied by severe autophagic or autophagic-necrotic degeneration of the cytoplasm. These results support the opinion of unclear distinction between different modes of cell death and indicate the involvement of autophagey in MNs neurodegeneration in vitro.

We morphologically examined human brains several years after a territorial ischemic stroke to assess the development of progressing white matter damage and its pathomechanisms. Our investigations focused on the role of TGF-beta, one of the factors whose expression increases after tissue damage, and its receptor endoglin in the propagation of postischemic injury. Examination of the white matter adjacent to the postapoplectic cavity revealed structural changes in the capillary vessels, disturbed microcirculation, and deep endothelial cell damage with DNA fragmentation in the TUNEL reaction. Many oligodendrocytes also revealed DNA damage and an increased expression of caspase-3. In the rarefied white matter, the microvessel immune reaction to TGF-beta was diminished while the expression of endoglin was heterogeneous: absent in some capillaries but increased in others in comparison to the vessels located more peripherally from the cavity and in the control material. We conclude that endoglin and TGF-beta can be involved in the development of the microangiopathy responsible for the propagation of postischemic white matter injury in humans. We suggest that disturbances in endoglin expression can influence TGF-beta signaling and, consequently, vessel structure and function. Pronounced endoglin expression can lead to decreased vessel wall integrity while a lack of the constitutively expressed protein is probably a mirror of deep vessel damage.

Biochemical and morphological observations of nerve roots in six fetuses from the 16th to 34th week of gestation and five infants 1 day to 3 years old are presented. In dorsal roots the process of myelination begins later than in the ventral roots and spinal cord and proceeds much slower. As in the spinal cord during nerve roots myelin maturation profound lipid changes are observed.

No abstract

Biochemical, light and electron microscopic observations in six human fetuses between the 16th and 34th weeks of gestation and five infants, 1 day to 3 years old, are presented. The results indicate that myelination of the human spinal cord started before the 16th week of gestation, as a considerable amount of myelin is isolated at this time biochemically, and occasionally axons with loose myelin coils are observed in the electron microscope. It is also stressed that morphological studies are insufficient to evaluate the completion time of the myelination process, as it can be shown biochemically that qualitative myelin maturation takes a long time.