Brain pathology
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Meningiomas account for approximately 30% of all primary central nervous system tumors and are found in half of neurofibromatosis type 2 patients often causing significant morbidity. Although most meningiomas are benign, 10% are classified as atypical or anaplastic, displaying aggressive clinical behavior. Biallelic inactivation of the neurofibromatosis 2 (NF2) tumor suppressor is associated with meningioma formation in all NF2 patients and 60% of sporadic meningiomas. ⋯ Previously, we inactivated Nf2 in homozygous conditional knockout mice by adenoviral Cre delivery and showed that Nf2 loss in arachnoid cells is rate-limiting for meningioma formation. Here, we report that additional nullizygosity for p16(Ink4a) increases the frequency of meningioma and meningothelial proliferation in these mice without modifying the tumor grade. In addition, by using magnetic resonance imaging (MRI) to screen a large cohort of mutant mice, we were able to detect meningothelial proliferation and meningioma development opening the way to future studies in which therapeutic interventions can be tested as preclinical assessment of their potential clinical application.
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Small regulatory RNAs are essential and ubiquitous riboregulators that are the key mediators of RNA interference (RNAi). They include microRNAs (miRNAs) and short-interfering RNAs (siRNAs), classes of approximately 22 nucleotide RNAs. miRNAs and siRNAs bind to Argonaute proteins and form effector complexes that regulate gene expression; in animals, this regulation occurs primarily at the post-transcriptional level. In this review, we will discuss our current understanding of how miRNA and siRNAs are generated and how they function to silence gene expression, focusing on animal and, in particular, mammalian miRNAs.
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Hypothermia (HT) by whole body (WBC) or selective head cooling (SHC) reduces hypoxic-ischemic (HI) brain injury; however, whether prolonged hypothermia and/or anesthesia disrupts immature brain development, eg, increases apoptosis, is unknown. Anesthesia increases apoptosis in immature animals. We investigated whether neuroprotective hypothermia and anesthesia disrupts normal brain development. ⋯ Immunohistochemical/histochemical analyses of neuronal, glial, endothelial, axonal, transcriptional apoptotic markers in areas devoid of histological lesions revealed no hypothermia/normothermia group and differences whether exposed to hypoxic-ischemic or not. Neither 36-h anesthesia nor 24-h hypothermia produced adverse effects at 4-day survival on a panel of brain maturation/neural death markers in newborn pigs. Longer survival studies are necessary to verify the safety of hypothermia in the developing brain.