Elastin-derived peptides: matrikines critical for glioblastoma cell aggressiveness in a 3-D system.

In the most common primary brain tumors, malignant glioma cells invade the extracellular matrix (ECM) and proliferate rapidly in the cerebral tissue, which is mainly composed of hyaluronan (HA) along with the elastin present in the basement membrane of blood vessels. To determine the role of ECM components in the invasive capacity of glioma cell lines, we developed a 3-D cell-culture system, based on a hydrogel in which HA can be coreticulated with kappa-elastin (HA-kappaE). Using this system, the invasiveness of cells from four glioma cell lines was dramatically increased by the presence of kappaE and a related, specific peptide (VGVAPG)(3). In addition, MMP-2 secretion increased and MMP-12 synthesis occurred. Extracellular injections of kappaE or (VGVAPG)(3) provoked a pronounced and dose-dependent increase in [Ca(2+)](i). kappaE significantly enhanced the expression of the genes encoding elastin-receptor and tropoelastin. We propose the existence of a positive feedback loop in which degradation of elastin generates fragments that stimulate synthesis of tropoelastin followed by further degradation as well as migration and proliferation of the very cells responsible for degradation. All steps in this ECM-based loop could be blocked by the addition of either of the EBP antagonists, lactose, and V-14 peptide, suggesting that the loop itself should be considered as a new therapeutic target.

The toxic effects of toluene on the optokinetic nystagmus in pigmented rats.

The effects of 375 mgm(-3) (100 ppm) toluene in air inhalation were evaluated on pigmented rats during either repeated exposures over five consecutive days 3h a day or during a single 4-h exposure. At the end of the inhalation period, the animals were returned to fresh air to evaluate their ability to recover optokinetic performance. The optokinetic responses were analyzed using a magnetic search coil technique previously described. After repeated toluene exposure, the eye position at rest of all the rats was unsteady. In response to visual stimulation, the eye velocity was slower and more irregular than in the control state. At the end of the stimulation, the environment of the animals became stationary, but the eye did not immediately return to a fixed stable position. A similar effect was observed after a single exposure. An increase of the optokinetic deficit was observed after single or repeated 375 mgm(-3) toluene exposures. No recovery was observed even after a single exposure. In view of the fact that toluene is a widely used solvent, these results show that inhalation of low concentrations, even for short single exposures, must be taken into account, because gaze destabilization could cause vertigo symptoms.

Labyrinthectomy decreases bone mineral density in the femoral metaphysis in rats.

To determine whether the vestibular system could influence bone remodeling in rats, we measured bone mineral density with dual energy X-rays absorptiometry before and 30 days after bilateral labyrinthectomy. Comparatively to intact control rats, labyrinthectomized animals showed a reduced bone mineral density in distal femoral metaphysis (p = 0.007): the variations between D0 and D30 were +3.0% for controls and -13.9% for labyrinthectomized rats. No significant difference between the 2 groups was observed in the whole body mineral density. These results suggest that the peripheral vestibular apparatus is a modulator of bone mass and more specifically in weight bearing bone. We discuss possible mechanisms of this vestibular influence probably mediated by the sympathetic nervous system.

Vestibular control on blood pressure during parabolic flights in awake rats.

The aim of this study was to evaluate the role of the vestibular system in cardiovascular control in a varying gravito-inertial field induced by parabolic flight. We measured variations in arterial pressure and heart rate in eight awake rats, four of which had undergone bilateral labyrinthectomy 3 months previously. While the control rats showed heart rate and mean arterial pressure modulations depending on gravity level, no such variation was observed in the lesioned rats. This study confirms the role of the vestibular system in cardiovascular control and opens up new prospects for interpreting cardiovascular variations observed during space flights.

Vestibular decompensation in labyrinthectomized rats placed in weightlessness during parabolic flight.

The purpose of this study was to determine whether the absence of gravitational cues during weightlessness could alter the posture and static eye deviation of Earth compensated rats with peripheral vestibular lesions. The responses of bilaterally (BL) and unilaterally (UL) labyrinthectomized rats at a compensated stage (40-43 days after lesion) during parabolic flight were compared with those at an acute stage (2-7 h after lesion) on Earth. When free-floating in 0 g, UL animals showed the same postural pattern as during water immersion just after surgery. The most striking observation was a continuous roll body motion at about 4 Hz, and a skewed asymmetric posture. When restrained in 0 g, static eye deviation was also comparable to that observed at an acute stage. A return to a compensated posture and gaze was observed within a few seconds following the end of the weightlessness conditions. BL animals were less affected. These results suggest that vestibular compensation after unilateral lesion can be disrupted momentarily and is a fragile state during which the otolith system in the remaining vestibular apparatus presumably plays a continuous role.