The aim of this study was to develop an MRI protocol to evaluate the growth and vascularity of implanted GL261 mouse gliomas on a 7T microimaging system. Both conventional T 1 -and T 2 -weighted imaging and dynamic, contrast-enhanced T 2 *-weighted imaging were performed on 34 mice at different stages of tumor development. MRI measurements of relative cerebral blood volume (rCBV) were compared to histological assessments of microvascular density (MVD). Enhancement on postcontrast T 1 -weighted images was compared to histological assessments of Evan's blue extravasation. Conventional High-grade gliomas, the most common primary brain tumors in humans, are also among the most vascularized malignant tumors. They have been widely studied in an attempt to understand the mechanisms underlying neovascularization or angiogenesis (1-4). Angiogenesis is considered a critical process in both the growth of solid tumors and the metastasis of tumor cells to distant sites (5,6).Furthermore, in gliomas the degree of neovascularization is critical in assessing tumor grade and malignancy, and in understanding tumor biology (7).Perfusion magnetic resonance imaging (pMRI) approaches have recently been developed to provide quantitative measures of cerebral microvasculature and hemodynamics (8,9). Relative cerebral blood volume (rCBV) measurements obtained from dynamic contrast-enhanced pMRI have shown promising correlations with both histologic grade and degree of neovascularization in human gliomas (9,10). Although pMRI has been widely used in brain tumor imaging, the exact relationship between imaging and pathologic findings has not been fully determined. In part, this is because full quantitative correlation between pMRI and histopathology requires a range of vascularity values that are difficult to obtain systematically in patients. In addition, it is not clear whether increases in pMRI-derived rCBV measurements are due to the dilation of existing vessels or to an increase in total number of neocapillaries, or both. Similarly, it is unclear at what stage in tumor development blood-brain barrier (BBB) breakdown and blood volume abnormalities become apparent on MRI.This study specifically addresses these issues by comparing high-field MRI with histopathology in an established mouse model of intracerebrally implanted GL261 glioma cells. The GL261 cell line is a well-established experimental glioma model that has been available through the National Cancer Institute Microbiological Associates (Bethesda, MD) since 1970 (11). GL261 cells grow well after intracerebral inoculation in C57BL/6 mice and demonstrate a moderate degree of invasiveness and infiltration (12). Tumor growth results in death of the mouse from mass effect in approximately 4 weeks, with a highly reproducible disease progression (13). Briefly, after implantation, tumor cells organize themselves around blood vessels during the first week, followed by a period of proliferation during the second week. Apoptosis in vascular cells and involution of the host blood vessels oc...

An experimental study on the rat sciatic nerve was performed to evaluate nerve regeneration through a collagen guide and to study the effects of alpha-melanocytic stimulating hormone (alpha-MSH) and basic fibroblast growth factor (b-FGF) in accelerating axonal elongation. After transection, nerves were repaired over a 7 mm gap using a placental collagen type IV guide. The channel was filled with either a b-FGF solution or an alpha-MSH solution or was produced with b-FGF incorporated into the guide. Four weeks later, only groups in which b-FGF had been injected or incorporated displayed a significant somatosensory evoked potential response. Histological and quantitative analysis of nerve fibres confirmed the existence of nerve continuity in groups receiving an alpha-MSH solution or a channel containing b-FGF. These results demonstrate that alpha-MSH in solution and b-FGF incorporated into a collagen type IV channel enhance peripheral nerve regeneration. However, at 4 weeks, only b-FGF (3 ng) restores functional activity.

The capacity of central nervous system (CNS) axons to elongate from the spinal cord to the periphery throughout a tubular implant joining the ventral horn of the spinal cord to an avulsed root was investigated in a model of brachial plexus injury. The C5-C7 roots were avulsed by controlled traction and the C6 root was bridged to the spinal cord over a 3 mm gap by the use of a collagen cylinder containing or not containing an autologous nerve segment, or an autologous nerve graft. Nine months later, the functionality and the quality of the axonal regrowth was evaluated by electrophysiology, retrograde labelling of neurons, and histological examination of the gap area. A normal electromyogram of the biceps was observed in all animals where the C6 root was bridged to the spinal cord. The mean average amplitude of the motor evoked potentials was comprised between 17.51 +/- 12.03 microV in animals repaired with a collagen cylinder, and 27.83 +/- 22.62 microV when a nerve segment was introduced in the tube. In nonrepaired animals spontaneous potentials reflecting a muscle denervation were observed at electromyography. Retrograde labelling indicated that a mean number of 58.88 +/- 37.89 spinal cord neurons have reinnervated the biceps in animals repaired with a tube versus 78.38 +/- 62.11 when a nerve segment was introduced in the channel, and 97.25 +/- 56.23 in nerve grafting experiments. Analyses of the repair site showed the presence of numerous myelinated regenerating axons. In conclusion, our results indicate that spinal cord neurons can regenerate through tubular implants over a 3 mm gap, and that this axonal regrowth appeared as effective as in nerve grafting experiments. The combination of an implant and a nerve segment did not significantly increase the regeneration rate.

In order to compare application of the roots of the phrenic nerve to the ansa hypoglossi for laryngeal muscle neurotization, 1 or more roots from the phrenic nerve were implanted into the right sternothyroid (RST) muscle of rabbits (n = 36). Controls were intact animals (in which RST innervation is provided by the ansa; n = 6) and denervated ones (n = 6). At 66 +/- 2 days (mean +/- SE) after neurotization, during quiet breathing, inspiratory electromyographic activity and isometric contraction force were observed in all reinnervated RST muscles (n = 24). During maximal inspiratory effort, electromyographic activity and force increased. In animals reinnervated by the C4 root alone, forces (46.22 +/- 7.8 g) were significantly higher than in intact animals (10.83 +/- 5.0 g). Retrograde labeling proved the phrenic origin of the neurotization. Electromyography of the diaphragm was recorded. We conclude that in rabbits, neurotization of a strap muscle by 1 or 2 roots of the phrenic nerve allows inspiratory contraction, even during quiet breathing. Such inspiratory activity is not observed in sternothyroid muscles of intact animals innervated by the ansa hypoglossi.