LIF promotes neurogenesis and maintains neural precursors in cell populations derived from spiral ganglion stem cells

<p>Abstract</p> <p>Background</p> <p>Stem cells with the ability to form clonal floating colonies (spheres) were recently isolated from the neonatal murine spiral ganglion. To further examine the features of inner ear-derived neural stem cells and their derivatives, we investigated the effects of leukemia inhibitory factor (LIF), a neurokine that has been shown to promote self-renewal of other neural stem cells and to affect neural and glial cell differentiation.</p> <p>Results</p> <p>LIF-treatment led to a dose-dependent increase of the number of neurons and glial cells in cultures of sphere-derived cells. Based on the detection of developmental and progenitor cell markers that are maintained in LIF-treated cultures and the increase of cycling nestin-positive progenitors, we propose that LIF maintains a pool of neural progenitor cells. We further provide evidence that LIF increases the number of nestin-positive progenitor cells directly in a cell cycle-independent fashion, which we interpret as an acceleration of neurogenesis in sphere-derived progenitors. This effect is further enhanced by an anti-apoptotic action of LIF. Finally, LIF and the neurotrophins BDNF and NT3 additively promote survival of stem cell-derived neurons.</p> <p>Conclusion</p> <p>Our results implicate LIF as a powerful tool to control neural differentiation and maintenance of stem cell-derived murine spiral ganglion neuron precursors. This finding could be relevant in cell replacement studies with animal models featuring spiral ganglion neuron degeneration. The additive effect of the combination of LIF and BDNF/NT3 on stem cell-derived neuronal survival is similar to their effect on primary spiral ganglion neurons, which puts forward spiral ganglion-derived neurospheres as an <it>in vitro </it>model system to study aspects of auditory neuron development.</p

Tenth and Twelfth Nerve Palsies in a Patient with Internal Carotid Artery Dissection Mistaken for Cervical Mass Lesion

Among the multiple causes for cranial nerve palsies, internal carotid artery dissection is rather uncommon. Patients usually present with unilateral head pain, Horner's syndrome, and signs of cerebral ischemia. We present the case of a 52-year-old male patient, who showed isolated palsies of the tenth and twelfth nerve without any other symptoms. Magnetic resonance imaging (T1) depicted a hyperintense lesion surrounding the internal carotid artery, which was mistaken for a cervical mass, and the patient underwent unnecessary surgical exploration of the neck. Angiography performed afterward could reveal the dissection of the internal carotid artery. This case shows that even in cases with mild and atypic symptoms, internal carotid artery dissection has always to be ruled out in lower cranial nerve palsies

Increased BrdU incorporation and increased number of neural progenitor cells in response to LIF treatment

<p><b>Copyright information:</b></p><p>Taken from "LIF promotes neurogenesis and maintains neural precursors in cell populations derived from spiral ganglion stem cells"</p><p>http://www.biomedcentral.com/1471-213X/7/112</p><p>BMC Developmental Biology 2007;7():112-112.</p><p>Published online 12 Oct 2007</p><p>PMCID:PMC2080640.</p><p></p> (): Quantification of BrdU-positive, nestin-positive, and BrdU/nestin-double positive cells 48 h after plating. Error bars indicate S.E.M., * indicates < 0.05, ** indicates < 0.01, = 8. Total cell numbers did not differ significantly when we compared LIF-treated with untreated cultures (1934 ± 403 and 2008 ± 435, respectively). (): Representative pictures of plated sphere-derived cells without LIF treatment (B), and with 10 ng/ml LIF (C). Scale bar = 200 μm. (): Higher magnification of two nestin-positive cells from (C) to illustrate the nuclear localization of the BrdU staining in one of the cells

Reduction of apoptotic cells in LIF treated sphere-derived cell cultures 48 h after plating

<p><b>Copyright information:</b></p><p>Taken from "LIF promotes neurogenesis and maintains neural precursors in cell populations derived from spiral ganglion stem cells"</p><p>http://www.biomedcentral.com/1471-213X/7/112</p><p>BMC Developmental Biology 2007;7():112-112.</p><p>Published online 12 Oct 2007</p><p>PMCID:PMC2080640.</p><p></p> Annexin-positive cells and annexin & nestin-double positive cell populations were significantly decreased in response to LIF. Error bars indicate S.E.M., * indicates < 0.05, ** indicates < 0.01, = 4. Total cell numbers did not differ significantly when we compared LIF-treated with untreated cultures (1124 ± 363 and 894 ± 516, respectively)