Enhanced wall shear stress prevents obstruction by astrocytes in ventricular catheters.

The treatment of hydrocephalus often involves the placement of a shunt catheter into the cerebrospinal ventricular space, though such ventricular catheters often fail by tissue obstruction. While diverse cell types contribute to the obstruction, astrocytes are believed to contribute to late catheter failure that can occur months after shunt insertion. Using in vitro microfluidic cultures of astrocytes, we show that applied fluid shear stress leads to a decrease of cell confluency and the loss of their typical stellate cell morphology. Furthermore, we show that astrocytes exposed to moderate shear stress for an extended period of time are detached more easily upon suddenly imposed high fluid shear stress. In light of these findings and examining the range of values of wall shear stress in a typical ventricular catheter through computational fluid dynamics (CFD) simulation, we find that the typical geometry of ventricular catheters has low wall shear stress zones that can favour the growth and adhesion of astrocytes, thus promoting obstruction. Using high-precision direct flow visualization and CFD simulations, we discover that the catheter flow can be formulated as a network of Poiseuille flows. Based on this observation, we leverage a Poiseuille network model to optimize ventricular catheter design such that the distribution of wall shear stress is above a critical threshold to minimize astrocyte adhesion and growth. Using this approach, we also suggest a novel design principle that not only optimizes the wall shear stress distribution but also eliminates a stagnation zone with low wall shear stress, which is common to current ventricular catheters.

Saccades and covert shifts of attention during active visual search: spatial distributions, memory, and items per fixation.

Target detection during active visual search was examined. The chance corrected spatial distribution of target detection was found to be symmetrically distributed around the point of fixation and, unexpectedly, was independent of the proximity of fixations to the display boundaries. Memory was found to play a very limited role in target detection, but a significant role in the guidance of eye movements. A model of covert shifts was used to estimate the number and spatial distribution of shifts required to explain observed performance. An increase from one to five shifts per fixation across increasing array set size as estimated by two different methods was inconsistent with unchanging fixation durations, suggesting that multiple covert shifts are not occurring during the fixations in active search.

Cortical image density determines the probability of target discovery during active search.

An analysis of target detection as a function of target eccentricity was made on eye movement data collected from three monkey subjects during active visual search. Target detection probability was invariant across array set size and eccentricity conditions when the cortical density of relevant stimuli surrounding the target was held constant. When target color was used to guide search, the effective cortical density was the density of stimuli that shared the target's color. Thus the passive constraint of cortical magnification in combination with an active selection for a stimulus attribute, in this case color, sets the spatial framework for detection of the target.

Effects of DFP on unit activity in rat superior colliculus.

The effect of systemically administered diisopropylfluorophosphate (DFP) on the spontaneous firing rate and light-evoked responses of rat superior colliculus neurons was determined from average histograms of single unit and multiunit activity. DFP produced a dose-dependent increase in superior colliculus spontaneous activity, and a decrease in light evoked activity. In many experiments, light evoked responses were completely abolished. The changes in spontaneous activity were reversible over a period of about 5 hours following DFP injection. These results establish the retino-tectal pathway as a major target of DFP toxicity.

Cerebral venous thrombosis. Demonstration with magnetic resonance angiography.

Three patients with cerebral venous thrombosis (CVT) were imaged with magnetic resonance angiography (MRA). Initial spin-echo magnetic resonance (MR) demonstrated acute or subacute thrombosis in all patients. The presence of thrombosis was confirmed with MRA. Repeat MRA in the three patients revealed partial recanalization in one and almost complete recanalization in two patients. The etiology of CVT is reviewed, and the advantages of MRA are compared with conventional MR imaging and computed tomography in the evaluation of CVT.

MR of post traumatic spinal cord lesions. Unexpected improvement of hemorrhagic lesions.

Fifteen patients who sustained spinal cord trauma were evaluated by MR within 72 hours of injury. Nine patients had hemorrhagic and six had nonhemorrhagic traumatic spinal cord lesions. Three patients with hemorrhagic and all six patients with nonhemorrhagic lesions showed some degree of neurological improvement on follow-up examinations. In two of the three patients with hemorrhagic lesions who improved, the hemorrhage was extensive. This supports the observation that hemorrhagic lesions are not always associated with a poor clinical outcome.

Transmitter release: prepackaging and random mechanism or dynamic and deterministic process.

Stepwise variations in end-plate potential amplitudes that are also multiples of spontaneous miniature end-plate potentials (MEPPs) demonstrate a quantal nature of evoked transmitter release at the vertebrate neuromuscular junction. Both the number of quanta which form relatively small end-plate potentials (EPPs) and the time intervals between MEPPs were found to fit Poisson statistics. These observations suggested that the release process randomly liberates uniform quantities of transmitter. Initial studies showed that quantal size remained stable after seemingly high rates of release which was interpreted to indicate that a large store of equally sized, equally available, and independently releasable quanta are present in the nerve terminals. The observation of numerous presynaptic vesicles that contain transmitter provided a morphological basis for prepacked transmitter (i.e., quanta). However, physiological studies over the last 15 years have yielded data that are difficult to incorporate into the quantum-vesicle hypothesis. With normal conditions and during most treatments which increase the rate of release, two classes of MEPPs have been found and both show a substructure. The bell-MEPP class was characterized by Fatt and Katz and the smaller skew-MEPP class has been studied by Kriebel. The ratio of the two classes and substructure compositions of both classes are variable. Short series of MEPPs and unitary EPPs (U-EPPs) show preferred amplitudes and longer series of MEPPs and U-EPPs show stepwise variations in amplitude. Slow-MEPPs and giant MEPPs belong to the skew class and represent nearly synchronous bursts of smaller MEPPs. Transmitter packet formation, preferred amplitudes, stepwise variations in amplitudes, random-like distributions and organized bursts can be simulated by a simple deterministic system, the drop formation process, that is known for its periodic and chaotic behaviors which are determined by the single parameter of flow rate. MEPP intervals, sizes and classes, are also dependent on rates of release which demonstrate that the release process(es) is highly organized and sensitive to different conditions. We demonstrate that the processes of drop formation and release of a packet of transmitter have similar properties and that deterministic characteristics describe MEPP and U-EPP time dependencies and amplitude substructures. The data and model presented here suggest that packet size of acetylcholine may be determined at the moment of release.

Exencephaly: sonographic findings and radiologic-pathologic correlation.

Exencephaly is a rare precursor of anencephaly in which a large amount of brain tissue is present despite the absence of the calvaria. It was discovered together with hydramnios in a near-term fetus. Sonographic, angiographic, and pathologic findings are discussed.

Further evidence for the dynamic formation of transmitter quanta at the neuromuscular junction.

Fatt and Katz (Nature 166:597-598, 1950; J Physiol 117:109-128, 1952) attributed miniature endplate potentials (MEPPs) to the action of a standard quantity of transmitter, the quantum (Del Castillo and Katz, J Physiol 124:560-573, 1954). Quantal packets of transmitter were proposed to be preformed (Del Castillo and Katz, In CNRS Paris (Ed): "Microphysiologie comparée des éléments excitables" 67:245-258, 1957) and stored in large numbers in the motor nerve terminal. Statistical analyses of intervals between MEPPs and numbers of quanta composing small endplate potentials indicated that quantal release was a random process and that release sites functioned independently of each other. With the discovery of synaptic vesicles it was proposed that each contained one quantum of transmitter. The quantal-vesicular hypothesis (Del Castillo and Katz, as cited above) fails, however, to explain amplitude distributions of MEPPs that are skewed and/or that show multiple peaks (Kriebel et al., Brain Res Review 15:167-178, 1990). The drop formation process (Shaw, "The Dripping Faucet as a Model Chaotic System," Santa Cruz, CA: Aerial Press, Inc., 1984) was shown to generate amplitude classes of drops that were similar to classes of MEPPs which suggested that rapid changes in quantal size and ratios of skew- to bell-MEPPs could be explained with a simple dynamic process which determines quantal size at the moment of release (Kriebel et al., as cited above, 1990). Further similarities between miniature endplate currents (MEPCs) and the formation of drops are reported here. We found that rapid changes in MEPC amplitudes and time courses, which accompany an increase in frequency, mimic changes in drop sizes that accompany increases in flow rate. MEPC intervals have a minimum and their distributions are comparable to those of drop intervals. During an increased rate of transmitter release, MEPP amplitudes and intervals were positively correlated. The results suggest that spontaneously released transmitter "packets" are formed at the moment of release and that transmitter supply to the process that forms packets is continuous.

The origin of thalamic inputs to the "hand" representation in the primary motor cortex.

We used retrograde transport of WGA-HRP to examine the origin of thalamic inputs to the "hand" representation in the primary motor cortex of macaques (Macaca nemestrina). Injections were placed in either the crest of the precentral gyrus or the rostral bank of the central sulcus. The sites for injection in the sulcus were determined by using intracortical stimulation to map the location of hand representation. We found that the precentral gyrus and central sulcus receive their predominant input from different subdivisions of the ventrolateral thalamus. Ventralis posterior lateralis pars oralis (VPLo) provides the most substantial input to a portion of the hand representation on the gyrus. In contrast, Ventralis lateralis pars oralis (VLo) provides the most substantial input to a portion of the hand representation in the sulcus. Prior studies have shown that VPLo is a major site of termination of cerebellar efferents and that VLo is a major site of termination of pallidal efferents. Thus, our results indicate that both the basal ganglia and the cerebellum "directly" influence the "hand" representation of the primary motor cortex.

Morphometric analysis of distinct microanatomy near the base of proximal tubule cells.

Models of cell shape in the rabbit S2 proximal renal tubule were derived from transmission electron micrographs and compared with scanning micrographs. Standard morphometric procedures were used to measure basolateral cell membrane surface density (SVt) relative to total epithelial volume in numerous zones of cell height. In the basal 20% region we also measured the volume fraction (F) of intercellular spaces and calculated new surface densities in reference only to the intercellular volume, SVi = SVt/F, or to the cellular volume, SVc = SVt/(1-F). Combined use of these surface densities then enabled us to calculate the diameter, length, and separation of effectively cylindrical microvilli at the cell base. Assuming that lateral cell membranes are radially oriented in the apical region but disposed on microvillus like structures of arbitrary orientation at the cell base, an improved cell model was developed that agreed with the scanning picture throughout the entire cell height. Basal microvillar elements contain approximately 60% of the total basolateral cell membrane surface area and possibly constitute a hydrostatic resistive region for absorbate flow. These features have interesting physiological implications.