Surgical considerations regarding cochlear implantation in the congenitally malformed cochlea.

A 4-year-old girl with congenital profound deafness underwent cochlear implant surgery. Preoperative CT and MRI revealed that her inner ears had common-cavity or aplasia-type malformation. The bilateral internal auditory meatus were markedly narrowed. Audiometric examination demonstrated that only slight residual hearing remained in the low-frequency range and that a hearing aid would be of no benefit. Cochlear implantation was performed in her left ear. Because of the abnormal position of the facial nerve, the routine facial recess approach could not be performed. A canal-wall-down mastoidectomy was performed, and multichannel cochlear implant electrodes were inserted by careful drilling of the bony wall of the semicircular canal area. All 22 electrodes were completely inserted into the cavity. The patient can perceive sounds and her hearing ability is progressively improving.

CNS myelinogenesis in vitro: time course and pattern of rat oligodendrocyte development.

Oligodendrocyte precursor cells that develop into myelin-forming cells of the central nervous system (CNS) were cultured from newborn rat brain to study how they proliferate and differentiate in normal conditioning medium, and their cell development was characterized by scanning electron microscopy (SEM) observation and immunocytochemical studies. We have identified A2B5-negative pre-O2A progenitor cells (so-called "type-1" oligodendrocytes) in the secondary cultures on the astrocyte feeder layer. These cells are very small (diameter: 3.5 microns), round, and glossy, and develop into the process-bearing O2A progenitor cells (called "type-2" oligodendrocytes), which also express myelin basic protein (MBP) both in the cell body and in their cell processes. Finally, they develop into mature oligodendrocytes (called "type-3" oligodendrocytes). After MBP expression is elicited in these cells and MBP accumulates in the cell process in the area in contact with the axon, these cells are capable of forming the myelin sheath. Therefore, we examined the mechanism of myelin-sheath formation of "type-3" oligodendrocytes using video time-lapse movies, and demonstrated that these cells initially sent out processes to search for axons several times before the onset of myelination. Then thick filopodia extended towards the axon, and at the same time, the axonal part of neuron moved forward. Finally the ruffling lamellipodial parts wrapped up the axon similarly to a transverse wave with the secured thick filopodial process on the axon acting as scaffolding. These results suggest that our experimental systems are useful in studying normal oligodendrocyte development and their cellular biochemistry, as well as investigating the mechanism of myelin formation by oligodendrocytes.

Visualization of a single myelination process of an oligodendrocyte in culture by video microscopy.

We described the initial events in the interaction between an oligodendrocyte process and an axon in culture utilizing video time-lapse microscopy. Myelination of an axon by the lamellipodium of an oligodendrocyte was achieved in several steps of cellular process development and coordinated interaction between axon and oligodendrocyte. The initial stage of contact included the formation of a lamellipodium process at the end of an oligodendrocyte process. It appeared that this process contacted the axon several times and was then retracted, and that the filopodia and lamellipodium underwent morphological changes prior to the onset of the myelination. In the second stage, the lamellipodium appeared to thicken and anchor to the axon. Finally, when rippling of the lamellipodial ruffling occurred, the angle between the anchoring filopodium and the axon changed depending on the direction of lamellipodial movement, and the lamellipodium, which was folded in layers, wrapped around the axon like a transverse wave in one motion as observed on the video screen. Thereafter, the lamellipodium assumed a "bursting" form within minutes in real time. This is the first comprehensive overview of how an oligodendrocyte plasma membrane wraps around an axon to form myelin.

Characterization of 5-hydroxytryptamine receptors on the isolated pig basilar artery by functional and radioligand binding studies.

5-Hydroxytryptamine (5-HT)-receptor subtypes on pig basilar arteries were investigated by measuring the contractile responses to 5-HT agonists, the effects of antagonists on the responses and by carrying out a radioligand binding assay with [3H]5-HT. The rank order of contractile agonist potency (according to the pEC50 values) was 5-carboxamidotryptamine > or = 5-HT > alpha-methyl-5-HT > (+/-)-8-hydroxy-dipropylaminotetralin. The contractile responses were not affected by endothelial denudation, and the 5-HT-induced contractions were antagonized competitively by ketanserin. Methiothepin shifted the 5-HT concentration-response curves to the right and downwards in a concentration-dependent manner. In the presence of ketanserin (10(-6) M), however, methiothepin antagonized the 5-HT-induced contractions competitively. Specific [3H]5-HT binding to 5-HT receptors was saturable, reversible and showed high (Kd, 2.5 nM) and low (Kd, 710 nM) affinities, with respective Bmax values of 29.5 and 1950 fmol/mg protein. These results indicate that both 5-HT1 and 5-HT2 receptors are present on pig basilar arterial smooth muscle cells, and their stimulation results in contraction.

How do oligodendrocytes ensheath and myelinate nerve fibers?

Oligodendrocyte precursor cells were cultured from newborn rat brain and studied their differentiation and proliferation. They have identified type-1, type-2, and type-3 oligodendrocytes based on the expression of characteristic marker molecules that frequently used to stage oligodendrocyte development. The type-3 oligodendrocytes were observed to send but tentative that locate axons prior to myelination. These processes terminate in lamellipodia, which eventually enwrap the axon and begin the myelination process with several steps. At the first stage, ruffling is immediately induced at the lamellipodia with filopodia made of oligodendrocyte processes, and the axon is contacted several times; then process retraction occurs to reform the filopodial and lamellipodial parts prior to the onset of the myelination. Second, after filopodial movements and lamellipodial ruffling occur again, their morphology is dramatically changed to become three thick filopodia that anchor to the axon. Finally, lamellipodial ruffling parts ripple, the angle between the position of the resting filopodium and the axon change, depending on the start of axonal movement, and the lamellipodia turn around the axon like a transverse wave with one stroke of the brush, as observed on the video screen, and their rolling membrane changes to the bursting form within minutes in real time.