Search bioRxivSearch

Biology subjects

Knowles, C. H.

Publications and source records attributed to Knowles, C. H..

2 recordsLinked to original sources

Species differences in the cerebellar distribution of six members of the Kv1 channel subfamily.

Comprehensive studies on the distribution of the Kv1 subfamily have been performed in rat (Chung et al., 2001) and gerbil (Chung et al., 2005), but not in mouse or human. We hypothesized that species differences may exist in the localization of these proteins. Two sets of polyclonal antibodies to Kv1.1-6 were used. Immunohistochemistry was performed on archived, formalin-fixed tissue from disease-free human, monkey and mouse cerebellum. Mouse staining corresponded to that described in rat and gerbil, with strong Kv1.1 and Kv1.2 immunoreactivities in the basket cell pinceau at the base of Purkinje cells. Kv1.3, Kv1.4, Kv1.5 and Kv1.6 were predominantly expressed in Purkinje cells. Human and monkey samples showed a similar pattern to mouse for Kv1.1, Kv1.2, Kv1.3 and Kv1.5. However, little or no Purkinje cell staining was seen in the primates with Kv1.4 and Kv1.6, and strong stellate cell expression was noted. All staining was abolished by cognate peptide blocking. Similar distributions were seen with both sets of antibodies. We conclude that there are marked species differences in the distribution of Kv1.4 and Kv1.6 between primates and rodents. Choosing appropriate animal models for studying physiological and disease processes may prove vital for translating research outcomes into clinical applications.

neuroscience

DyNeuMo Mk-1: A Fully-Implantable, Motion-Adaptive Neurostimulator with Configurable Response Algorithms

There is growing interest in using adaptive neuro-modulation to provide a more personalized therapy experience that might improve patient outcomes. Current implant technology, however, can be limited in its adaptive algorithm capability. To enable exploration of adaptive algorithms with chronic implants, we designed and validated the Picostim DyNeuMo Mk-1 (DyNeuMo Mk-1 for short), a fully-implantable, adaptive research stimulator that titrates stimulation based on circadian rhythms (e.g. sleep, wake) and the patients movement state (e.g. posture, activity, shock, free-fall). The design leverages off-the-shelf consumer technology that provides inertial sensing with low-power, high reliability, and relatively modest cost. The DyNeuMo Mk-1 system was designed, manufactured and verified using ISO 13485 design controls, including ISO 14971 risk management techniques to ensure patient safety, while enabling novel algorithms. The system was validated for an intended use case in movement disorders under an emergency-device authorization from the Medicines and Healthcare Products Regulatory Agency (MHRA). The algorithm configurability and expanded stimulation parameter space allows for a number of applications to be explored in both central and peripheral applications. Intended applications include adaptive stimulation for movement disorders, synchronizing stimulation with circadian patterns, and reacting to transient inertial events such as posture changes, general activity, and walking. With appropriate design controls in place, first-in-human research trials are now being prepared to explore the utility of automated motion-adaptive algorithms.

bioengineering