Anna Taraszewska

Autophagic Degeneration of Motor Neurons in a Model of Slow Glutamate Excitotoxicity in Vitro

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-β-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.

Mutations in the von Hippel-Lindau Tumour Suppressor Gene in Central Nervous System Hemangioblastomas

Central nervous system hemangioblastomas (cHAB) are rare tumours which most commonly arise in the cerebellum. Most tumours are sporadic, but as many as one third of cHABs occur in the course of the hereditary disorder - von Hippel-Lindau disease (VHL). In order to diagnose new VHL families in Poland we performed sequencing of the entire VHL gene in archival material (paraffin embedded hemangioblastoma tissues) in a large series of 203 unselected patients with cHAB. VHL gene mutations were detected in 70 (41%) of 171 tumour samples from which DNA of relatively good quality was isolated. We were able to obtain blood samples from 19 of mutation positive cases. Eight (42%) of these harboured germline mutations in persons from distinct undiagnosed VHL families.

Microsurgical third ventriculostomy

Objective The neurosurgical approach through the lamina terminalis (LT) is a commonly used technique for management of the third ventricle region pathology. Furthermore, LT fenestration is a recommended procedure during surgery of ruptured intracranial aneurysms. Though the LT is a rudimentary structure in adult human brain, its neurosurgical significance is eliciting increasing interest. The aim of the presented study is to characterize the LT histologically, with special attention to the previously recommended area of LT fenestration and to the localization and structure of the organum vasculosum lamina terminalis (OVLT). Methods The study was performed on tissue sampled from eight formalin-fixed brains. Paraffin sections taken from various levels of the LT were routinely stained with hematoxylin and eosin (H&E) and by immunohistochemical methods. Results The LT in the inferior part bordering the optic recess and immediately above the optic chiasm exhibited paucicellular, mainly fibrillar, glial tissue with scanty neural elements and small vessels. At about halfway along the length of the LT an area of loose structure, with an increased number of glial cells, small neurons and thin-walled vessels corresponding to the OVLT was observed. In the majority of examined cases the OVLT was poorly developed and was therefore sometimes overlooked. The superior segment of the LT near the anterior commissure disclosed again paucicellular and slightly loosened fine fibrillar tissue. Conclusions The results of the present microscopic study confirm the opinion that the inferior segment of the LT is the most convenient place for safe incision. Its thinnest middle part immediately above the optic recess is composed mainly of gliotic tissue. Above, prominent loosened tissue and the rather rudimental structure of the OVLT seem to be additional favorable factors for a safe fenestration of the LT.