Vascular disruptions including blood-brain barrier breakdown and pathologic angiogenesis contribute to the development of epilepsy in normal brains. The Notch signaling pathway is activated in response to seizure activity, and its activation promotes seizures, although its exact role in angiogenesis is poorly understood. Here, we have examined the role of Notch signaling in angiogenesis in a kainic acid-induced mouse model of epilepsy. We show that following seizures, expression of the Notch ligand Jagged1 in the hippocampus is upregulated in astrocytes and levels of activated Notch1 are increased in endothelial cells. Using an in vitro model of angiogenesis, we provide evidence that brain endothelial tube formation is promoted in the presence of astrocytes. Isolated primary brain endothelial cells develop significantly longer vascular sprouts when cultured in the presence of astrocytes. Notch1 signaling is activated in brain endothelial cells cocultured with astrocytes, and astrocytic Jagged1 expression is required for angiogenic enhancement, as shown by the inhibitory effect of Jagged1 small interfering RNA (siRNA) expression in astrocytes on endothelial cell vascular sprouting in vitro. Therapies targeting the Jagged1/Notch1 signaling pathway may therefore be effective in limiting aberrant angiogenesis following status epilepticus.
We herein report two cases of post-treatment maturation of medulloblastoma (MB).
We also conducted a literature review to summarize the clinical and pathologic
features of MB maturation. From January 1992 to February 2017, 52 patients with
MB underwent surgical resection followed by radiotherapy and chemotherapy. Tumor
cell maturation was identified in two patients who underwent a second surgery.
We conducted a systematic search of PubMed and identified six such cases. In
both of our patients, the pathologic type was MB with extensive nodularity
(MBEN). Both patients underwent radiotherapy and chemotherapy. The tumor
differentiated to gangliocytoma in both patients. In the overall analysis that
also included the six cases identified in the literature, the pathologic types
were classic MB (n=1), desmoplastic/nodular MB (n=2), MBEN (n=3), and
unclassified MB (n=2). MB differentiated into the following types: gangliocytoma
(n=2), ganglioglioma (n=1), melanocyte (n=1), neuronal differentiation (n=2),
and classic MB (n=1). Desmoplastic/nodular MB and MBEN can differentiate into
less malignant cells types after radiotherapy and chemotherapy. Maturation of MB
may be affected radiotherapy and chemotherapy.
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