Neural precursor cells contribute to adult neurogenesis and to limited attempts of brain repair after injury. Here we report that in a murine experimental glioblastoma model, endogenous neural precursors migrate from the subventricular zone toward the tumor and surround it. The association of endogenous precursors with syngenic tumor grafts was observed, after injecting red fluorescent proteinlabeled G261 cells into the caudate-putamen of transgenic mice, which express green fluorescent protein under a promoter for nestin (nestin-GFP). Fourteen days after inoculation, the nestin-GFP cells surrounded the tumors in several cell layers and expressed markers of early noncommitted and committed precursors. Nestin-GFP cells were further identified by a characteristic membrane current pattern as recorded in acute brain slices. 5-Bromo-2-deoxyuridine labeling and dye tracing experiments revealed that the tumor-associated precursors originated from the subventricular zone. Moreover, in cultured explants from the subventricular zone, the neural precursors showed extensive tropism for glioblastomas. Tumor-induced endogenous precursor cell accumulation decreased with age of the recipient; this correlated with increased tumor size and shorter survival times in aged mice. Coinjection of glioblastoma cells with neural precursors improved the survival time of old mice to a level similar to that in young mice. Coculture experiments showed that neural precursors suppressed the rapid increase in tumor cell number, which is characteristic of glioblastoma, and induced glioblastoma cell apoptosis. Our results indicate that tumor cells attract endogenous precursor cells; the presence of precursor cells is antitumorigenic; and this cellular interaction decreases with aging.

Oligoastrocytomas are heterogeneous tumors that have molecular features that overlap with either oligodendrogliomas or astrocytomas. Differences in the frequency of chromosomal losses of 1p and 19q in oligodendrogliomas are related to tumor location, with a low rate of allelic loss in tumors of the temporal and a high rate in tumors of the frontal, parietal, and occipital lobes. To test the possibility of regional molecular heterogeneity in oligoastrocytoma, we examined a series of 203 gliomas including 68 oligoastrocytomas and two control groups of 73 oligodendrogliomas and 62 astrocytomas for allelic losses of chromosomal arms 1p and 19q, and TP53 mutations, and compared these data with tumor localization. Common molecular alterations were found in oligodendrogliomas and oligoastrocytomas arising in extratemporal sites. In respect to the molecular parameters analyzed, temporal oligoastrocytomas were either indistinguishable from astrocytoma or similar to temporal oligodendrogliomas. Oligodendroglial neoplasms can thus be separated into three molecular subsets, two of which include lesions with the morphological features of oligodendrogliomas and oligoastrocytomas and one resembling temporal oligoastrocytoma. Molecular subclassification thus unifies previous findings about prognosis, behavior, response Oligodendroglial tumors, including oligodendrogliomas and oligoastrocytomas, constitute between 5% and 18% of all primary human brain tumors.1-4 Advances in diagnostic recognition and clinical management have succeeded in a dramatic improvement of the clinical outcome of patients with anaplastic oligodendroglioma. Distinct molecular subsets of oligodendroglial tumors also have highly differential responses to therapy. 5,6 Therefore, the further identification and evaluation of diagnostic parameters with high prognostic power is of great interest in oligodendroglial neoplasms.Somatic deletions on the short arm of chromosome 1 [loss of heterozygosity (LOH) 1p] and the long arm of chromosome 19 (LOH 19q) are typical of oligodendroglioma and oligoastrocytoma. [7][8][9][10][11][12] To date, however, neither the 1p nor 19q gene has been identified. Although LOH 19p is also frequently seen in anaplastic astrocytomas and may be associated with tumor progression, LOH 1p is more closely associated with oligodendroglial gliomas. 13 The combination of LOH 1p and LOH 19q is observed only rarely in gliomas other than oligodendroglioma and oligoastrocytoma. 11Oligoastrocytomas exhibit both astrocytic and oligodendroglial morphologies.14 Because of the rather vague criteria for defining oligoastrocytoma, the incidence of oligoastrocytoma varies considerably between different studies. Based on molecular findings, oligoastrocytomas occupy an intermediate position between oligodendrogliomas and astrocytomas. From 30 to 70% of oligoastrocytomas show LOH 1p and LOH 19q 8 -12,15 thus genetically resembling oligodendrogliomas, whereas ϳ30% show mutations in the TP53 gene or LOH 17p 10,16 suggesting a relation to astrocytomas. Signific...

The purpose of this study was the application of the proton-resonance-frequency method to monitor laser-induced interstitial thermotherapy (LITT) in a patient with an astrocytoma WHO II. A phase-sensitive two-dimensional (2D) fast low-angle shot (FLASH) sequence was used to determine the temperature-related phase shifts during LITT. Temperature maps were displayed during therapy with a temporal resolution of 20 seconds. Irradiation was discontinued as soon as the 60 to 65 degrees C isotherm reached the margin of the tumor. A contrast-enhanced MRI study performed immediately after therapy showed a good correlation of the size of an enhancing rim around the lesion with the 60 to 65 degrees C isotherm. The preliminary results of our study indicate that MRI guidance of LITT may be improved by temperature quantification based on the proton-resonance-frequency method.

The lack of classical lymph vessels within brain tissue complicates immune surveillance of the CNS, and therefore, cellular emigration out of the CNS parenchyma requires alternate pathways. Whereas invasion of blood-derived mononuclear cells and their transformation into ramified, microglia-like cells in areas of axonal degeneration across an intact BBB have been demonstrated, it still remained unclear whether these cells reside permanently, undergo apoptosis, or leave the brain to present antigen in lymphoid organs. With the use of ECL of mice and injection of GFP-expressing monocytes, we followed the appearance of injected cells in spleen and LNs and the migratory pathways in whole-head histological sections. Monocytes migrated from the lesion site to deep CLNs, peaking in number at Day 7, but they were virtually absent in spleen and in superficial CLNs and inguinal LNs until Day 21 after lesion/injection. In whole-head sections, GFP monocytes were found attached to the olfactory nerves and located within the nasal mucosa at 48 hpi. Thus, monocytes are capable of migrating from lesioned brain areas to deep CLNs and use the cribriform plate as an exit route.

Our data provide evidence for the reorganization of the human motor cortex to allow for preserved hand function in Grade II astrocytomas.