The prenatal development of the neurons immunoreactive for high-affinity tropomycin-related kinase (trk) receptor (pan trk which recognizes trkA, trkB, and trkC) and low-affinity p75 neurotrophin receptor (p75NTR) was examined in the human brain from embryonic weeks 10 to 34 of gestation. In the embryonic week 10 specimen in which only brainstem regions were available for evaluation, trk immunoreactivity (trk-ir) was observed in the ventral cochlear, solitary, raphe, spinal trigeminal, and hypoglossal nuclei, as well as the vestibular complex and medullary reticular formation. At this time point of gestation, p75ntr-immunoreactive (p75NTR-ir) staining was observed within these same regions plus the inferior olivary and ambiguus nuclei. At embryonic week 14, trk-ir neurons were seen within the subplate zone of the entorhinal cortex, basal forebrain, caudate nucleus, putamen, external segment of the globus pallidus, specific thalamic nuclei, lateral mammillary nucleus, habenula nucleus, select brainstem nuclei, and the dentate nucleus of cerebellum. At this gestational time point, p75NTR-ir neurons were observed in each of these structures, with the exception of the caudate nucleus, specific thalamic nuclei, lateral mammillary nucleus, and habenula nucleus. Additionally, p75NTR-ir neurons were observed within the corpus callosum. The staining pattern for both trk and p75NTR remained unchanged at embryonic weeks 15 to 16 except for the addition of trk-ir and p75NTR-ir within the cortical subplate zone, hippocampus, and subthalamic nucleus. By embryonic week 18, trk-ir neurons were widely expressed within mostly all thalamic nuclei. In contrast, trk-ir was no longer seen within the hypoglossal, cuneate, and gracile nuclei at this time point. This staining pattern for trk and p75NTR remained virtually unchanged from embryonic weeks 19 to 20 and embryonic weeks 16 to 20, respectively. From embryonic weeks 22 to 34, the distribution of both trk-ir and p75NTR-ir neurons changed gradually. During this period, neurons in most thalamic and some brainstem nuclei became progressively immunonegative for trk, whereas neurons in the neocortical subplate zone, corpus callosum, and hilar region of dentate gyrus gradually lost immunoreactivity for p75NTR. These data demonstrate an important and complex role for both the high-(trk) and low- (p75) affinity neurotrophin receptors during the development of multiple neuronal systems in the human brain.

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The present work formulates and analyzes the inhibitory effect of anti-angiogenic factor angiostatin excreted by the primary tumor on metastatic tumor angiogenesis, blood perfusion, and interstitial fluid flow in the tumor microenvironment by means of a numerical experiment. The simulation results demonstrate that angiostatin has an obvious impact on the morphology, growth rate, and the number of branches of microvascular network inside and outside the metastatic tumor, and angiostatin has the capacity to regulate and inhibit the formation of new blood vessels. Heterogeneous blood perfusion, widespread interstitial hypertension, and low convection within the metastatic tumor have obviously improved under the inhibitory effect of angiostatin, which are consistent with physiological observed facts. The simulation results may provide beneficial information and theoretical models for clinical research of anti-angiogenic therapy strategies.