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Plasma Neutrons Effects on Nervous System

#2599


The Study of Thermo-Nuclear Neutron Irradiation on the Structure of Synaptic Connections in the Central Nervous System of the Rat and Protective Opportunity of Hypothermia

Tech Area / Field

  • BIO-RAD/Radiobiology/Biotechnology
  • BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology

Status
3 Approved without Funding

Registration date
03.09.2002

Leading Institute
Institute of Cell Biophysics, Russia, Moscow reg., Puschino

Supporting institutes

  • VNIIEF, Russia, N. Novgorod reg., Sarov

Collaborators

  • Brandeis University / Department of Biology and Volen Center for Complex System, USA, MA, Waltham\nOpen University, UK, Walton Hall\nUniversity of Florida / College of Medicine, USA, FL, Gainesville

Project summary

The neutron radiation has been used in oncology basically as a means of radiotherapy of inoperable tumors including brain tumors. A malignant transformation occurs most often in auxiliary astroglial cells of the brain. Glial cells support nerve cells (neurons) and create conditions for their normal functioning. They are distributed among neurons and their fibers in all parts of the brain. Diffused tumors growing from them can be located in deep structures of the brain where their surgical removal is often impossible, since the vital nervous centers can thus be impaired. High penetrating ability of the neutron irradiation gives, in such cases, a unique opportunity to destroy tumor cells without opening up the brain. Comparative studies carried out on the effect of neutron and gamma irradiation on the condition of human patients with diffused tumors do not allow to come to a certain conclusion with respect to their therapeutic efficiency. This is probably due to the fact that any irradiation induces not only oncostatic effect causing death of malignant cells, but also cytotoxic effect, damaging normal cells localized near tumor cells. At the same time, there are virtually no ways to estimate cytotoxic action of irradiation in a living brain. To determine the expediency of clinical application of thermonuclear neutron irradiation in radiotherapy of brain tumors it is necessary to understand the action of neutrons on healthy cells, both nerve and glial, and to clarify, first, how badly irradiation side-effects may affect the normal activity of the central nervous system (c.n.s.), and, second, to what degree the injuries are reversible.

In this connection we will carry out a detailed morphological analysis of a 3D organization of interneuronal (synaptic) contacts (synapses) in the rat brain immediately on neutron irradiation and at different time intervals subsequently in the course of the brain functions recovery. The newest methods of the quantitative electron microscopic analysis (ultrathin serial sections) will be applied for this purpose which allows to obtain three-dimensional images of synapses between neurons and to estimate their number and efficiency. This research will give an answer to the question if the damages in brain functioning caused by thermonuclear neutron irradiation are connected with a loss of some contacts between neurons or they are caused by the injury of the functional state of neurons. If the structural changes of contacts between neurons are revealed, it is possible to estimate the degree of their reversibility. The analysis of interaction between processes of both nerve and glial cells, basic and auxiliary elements of the nervous tissue, is also supposed to follow.

One of the ways to block the development of pathological changes in the brain under the effect of various damaging factors consists in its cooling. This treatment is even used in surgical practice. To check up whether and how effectively the cooling can enhance the stability of interneuronal contacts in the brain on neutron irradiation it is suggested to irradiate the rats both in usual normothermic conditions and in hypothermia. A special chamber provides limitation in oxygen supply and simultaneous cooling of the rat which induces the transition of the rat into a state when the temperature of its body is reduced down to 16-20 °C.

In the realization of the given project new basic data will be obtained regarding possible reversible structural synaptic reorganizations of neuron network; particularly, on redistribution of glial processes localized around the neuronal processes during the development of pathological phenomena caused by neutron irradiation and associated with damage to brain cells.

The obtained data can become also the basis for defining the parameters of devices and modes of neutron irradiation to be used in medicine, which make the damage of healthy brain cells minimal and/or quickly compensated for. Some recommendations will be developed for updating safety standards when working with sources of thermonuclear neutron radiation.


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