Radiation-induced neurovascular injury

International audienc

Effets neurochimiques précoces de l’irradiation globale aigüe sur le système nerveux central adulte

Le système nerveux central adulte fut longtemps considéré comme très radiorésistant. Le développement de techniques sensibles et spécifiques a amené les radiobiologistes à réviser ce concept. Notre laboratoire s'est particulièrement intéressé aux perturbations neurochimiques induites au cours du syndrome initial d'irradiation globale aiguë. Nous présentons les principaux résultats expérimentaux obtenus sur les systèmes dopaminergique et cholinergique

Involvement of the central nervous system in radiation-induced multi-organ dysfunction and/or failure.

International audienceThe presence of multiple organ dysfunction syndrome (MODS) in victims of the recent accidents in Nesvizh and Tokai-mura suggests that radiation-induced systemic inflammatory response syndrome (SIRS) occurs in acute radiation sickness (ARS). Multiple organ failure (MOF) refers to the gradual and sequential failure of organs occurring after a wide spectrum of insults. MOF is believed to be the consequence of the host's response to the insult and is strongly linked to SIRS. It is believed that SIRS is mediated by endogenous regulators that are released during the acute phase reaction. The resulting interplay of cytokines may compromise homeostasis of various organ systems, resulting in MODS. In the classical description of ARS, the role of the central nervous system (CNS) has been underestimated. Today, it is recognised that the CNS is a radiosensitive organ whose degree of dysfunction can be quantified by electrophysiological, biochemical and/or behavioural parameters. Abnormalities in CNS function defined by these parameters may occur at a low dose of whole body radiation. The evolving concept of radiation-induced MODS in ARS provides a framework for evaluating injury to the CNS. Ionising radiation also induces an inflammatory response that may be specific to the CNS. This response is observed after either local irradiation of the CNS or whole body irradiation. The relationship between inflammatory responses in the CNS and the peripheral nervous system is undefined. Whether or not the CNS inflammatory response syndrome is a consequence of SIRS or is an independent syndrome remains an open question. The answer to this question may have implications regarding therapy and medical management of irradiated victims

IL-1beta, TNFalpha and IL-6 induction in the rat brain after partial-body irradiation: role of vagal afferents.

International audiencePURPOSE: To evaluate the central nervous system neuroimmune and inflammatory responses during the prodromal phase of the acute irradiation syndrome in rat brains after partial-body exposure (head-protected) and to investigate the potential neural signalling pathways from the irradiated periphery to the non-irradiated brain. MATERIAL AND METHODS: The study included four groups of rats: one irradiated group and one sham irradiated group, each containing non-vagotomized and vagotomized rats. In vagotomized rat groups, the subdiaphragmatic vagal section surgery was carried out 45 days before the irradiation exposure. The rats were partial-body irradiated with the head shielded with (60)Co gamma-rays to a dose of 15 Gy. They were sacrificed 6 h after the end of exposure. The hypothalamus, hippocampus, thalamus and cortex were then collected, and the concentrations of IL-1beta, TNFalpha and IL-6 in each were measured by ELISA assays. RESULTS: Six hours after irradiation, IL-1beta levels had increased in the hypothalamus, thalamus and hippocampus, and TNFalpha and IL-6 levels had increased significantly in the hypothalamus. Vagotomy before irradiation prevented these responses. CONCLUSIONS: It was concluded that the hypothalamus, hippocampus, thalamus and cortex react rapidly to peripheral irradiation by releasing pro-inflammatory mediators. The results also show that the vagus nerve is one of the major ascending pathways for rapid signalling to the brain with respect to partial body irradiation

Real-time spike detection in EEG signals using the wavelet transform and a dedicated digital signal processor card

Describes a complete real-time system for EEG signal analysis. Specific software and hardware have been designed to provide biologists with an efficient tool, which allows a complete study of the different states of vigilance as well as the paroxysmal activities. The analysis method which is based on the wavelet transform is first presented and compared to the standard spectral approach. The dedicated digital signal processor card, based on the Motorola 96002 processor chip, that has been designed to support real-time acquisition and real-time processing of EEG signals is then presented. The authors finally illustrate the proposed method by processing real EEG signals of rats, and show that it opens up new prospects in the domain of EEG-based diagnosis. The authors propose a new representation, called globalization, that provides a global view and better detection of paroxysmal activities

Neuroimmune response and sleep studies after whole body irradiation with high-LET particles

International audienceIn order to investigate the biological effects of galactic rays on astronaut cerebral functions after space flight, mice were exposed to different heavy ions (HZE) in whole-body conditions at doses comparable to the galactic flux: 12C, 16O and 20Ne (95 MeV/u, at 42– 76 mGy). Animals were also exposed to 42 mGy of 60Co radiation for comparison with HZE. The neuroimmune response, evaluated by interleukin-1 (IL-1) measurement, showed that this cytokine was produced 3 h after irradiation by 16O or 60Co. In contrast, neither 12C (56.7 mGy) nor 20Ne (76 mGy) induced IL-1 production. However, immunohistochemical staining of 12C-irradiated mouse brain tissue showed 2 months later a marked inflammatory reaction in the hippocampus and a diffuse response in parenchyma. Sleep studies were realized before and after exposure to 42 mGy of 16O and 76 mGy of 20Ne: only the 20Ne radiation displayed a small effect. A slight decrease in paradoxical sleep, corresponding to a reduction in the number of episodes of paradoxical sleep, was manifested between 8 and 22 days after exposure. Exposure to 12C and 16O induced no changes either in cellularity of spleen or thymus, or in caspase 3 activity (as much as four months after irradiation). Taken together, these data indicate that the CNS could be sensitive to heavy ions and that responses to HZE impact depend on the nature of the particle, the dose threshold and the time delay to develop biological processes. Differences in responses to different HZE highlight the complex biological phenomena to which astronauts are submitted during space flight