Isolation and Characterization of Neural Stem Cells from the Rat Inferior Colliculus.

The inferior colliculus (IC) is a nucleus of the auditory pathway and its fourth relay station. It integrates afferent information from the superior olivary complex and the cochlear nucleus. To date, no causal therapeutic options are known for damaged neuronal structures in this area. Regenerative medicine offers a potential approach to causally treating hearing impairment. After neural stem cells had been identified in certain areas of the auditory pathway, the question arouses, whether the IC also has a neurogenic potential. Cells from the IC of postnatal day 6 rats were extracted and cultured as neurospheres. Cells in the neurospheres showed mitotic activity and positive stain of neural stem cell markers (Nestin, DCX, Atoh1, and Sox-2). In addition, single cells were differentiated into neuronal and glial cells shown by the markers ß-III-tubulin, GFAP, and MBP. In summary, basic stem cell criteria could be detected and characterized in cells isolated from the IC of the rat. These findings will lead to a better understanding of the development of the auditory pathway and may also be relevant for identifying causal therapeutic approaches in the future.

Pathophysiology of esophageal impairment due to button battery ingestion.

BACKGROUND: The increased use of button batteries with high energy densities in devices of daily life presents a high risk of injury, especially for toddlers and young children. If an accidental ingestion of a button battery occurs, this foreign body can become caught in the constrictions of the esophagus and cause serious damage to the adjacent tissue layers. The consequences can be ulcerations, perforations with fistula formation and damage to the surrounding anatomical structures. In order to gain a better understanding of the pathophysiology after ingestion, we carried out systematic studies on fresh preparations of porcine esophagi. METHODS: The lithium button battery type CR2032, used most frequently in daily life, was exposed in preparations of porcine esophagi and incubated under the addition of artificial saliva at 37 °C. A total of eight esophagi were analysed by different methods. Measurements of the pH value around the battery electrodes and histological studies of the tissue damage were carried out after 0.5-24 h exposure time. In addition, macroscopic time-lapse images were recorded. Measurements of the battery voltage and the course of the electric current supplemented the experiments. FINDINGS: The investigations showed that the batteries caused an electrolysis reaction in the moist environment. The positive electrode formed an acidic and the negative electrode a basic medium. Consequently, a coagulation necrosis at the positive pole, and a deep colliquation necrosis at the minus pole occurred. After an exposure time of 12 h, tissue damage caused by the lye corrosion was observed on the side of the negative electrode up to the lamina muscularis. The corrosion progressed up to the final exposure time of 24 h, but the batteries still had sufficient residual voltage, such that further advancing damage would be expected. CONCLUSIONS: Button battery ingestion in humans poses an acute life-threatening danger and immediate endoscopic removal of the foreign body is essential. After only 2 h exposure time, significant damage to the tissue could be detected, which progressed continuously to complete esophageal perforation. The primary prevention of battery ingestion is therefore of particular importance.

Cochlear nucleus whole mount explants promote the differentiation of neuronal stem cells from the cochlear nucleus in co-culture experiments.

The cochlear nucleus is the first brainstem nucleus to receive sensory input from the cochlea. Depriving this nucleus of auditory input leads to cellular and molecular disorganization which may potentially be counteracted by the activation or application of stem cells. Neuronal stem cells (NSCs) have recently been identified in the neonatal cochlear nucleus and a persistent neurogenic niche was demonstrated in this brainstem nucleus until adulthood. The present work investigates whether the neurogenic environment of the cochlear nucleus can promote the survival of engrafted NSCs and whether cochlear nucleus-derived NSCs can differentiate into neurons and glia in brain tissue. Therefore, cochlear nucleus whole-mount explants were co-cultured with NSCs extracted from either the cochlear nucleus or the hippocampus and compared to a second environment using whole-mount explants from the hippocampus. Factors that are known to induce neuronal differentiation were also investigated in these NSC-explant experiments. NSCs derived from the cochlear nucleus engrafted in the brain tissue and differentiated into all cells of the neuronal lineage. Hippocampal NSCs also immigrated in cochlear nucleus explants and differentiated into neurons, astrocytes and oligodendrocytes. Laminin expression was up-regulated in the cochlear nucleus whole-mounts and regulated the in vitro differentiation of NSCs from the cochlear nucleus. These experiments confirm a neurogenic environment in the cochlear nucleus and the capacity of cochlear nucleus-derived NSCs to differentiate into neurons and glia. Consequently, the presented results provide a first step for the possible application of stem cells to repair the disorganization of the cochlear nucleus, which occurs after hearing loss.