Preclinical evaluation of a miniaturized Deep Brain Stimulation electrode lead.

The effect of miniaturizing the electrode lead for Deep Brain Stimulation (DBS) therapy was investigated in this work. A direct comparison was made between a miniature lead (0.65 mm diameter) and a lead of standard size (1.3 mm). Acute in vivo implantation in two cat brains was performed to evaluate surgical trauma and confirm capacity to target thalamic nuclei. Insertion into a homogeneous gel model of neural tissue was used to compare insertion forces while visualizing the process. The standard size cannula, used first to guide lead insertion, required substantially higher insertion force compared with the miniature version and produced a significantly larger region of tissue disruption. The characteristic hemorrhage and edema extended 119-352 µm from the implanted track surface of the miniature lead and cannula, while these extended 311-571 µm for the standard size lead and cannula. A miniature DBS implant can reduce the extent of trauma and could potentially help improve neural function preservation after functional neurosurgery.

Cytoskeletal changes during development and aging in the cortex of neurofilament light protein knockout mice.

The neurofilament light (NFL) subunit is considered as an obligate subunit polymer for neuronal intermediate filaments comprising the neurofilament (NF) triplet proteins. We examined cytoskeletal protein levels in the cerebral cortex of NFL knockout (KO) mice at postnatal day 4 (P4), 5 months, and 12 months of age compared with age-matched wild-type (WT) mice of a similar genetic background (C57BL/6). The absence of NFL protein resulted in a significant reduction of phosphorylated and dephosphorylated NFs (NF-P, NF-DP), the medium NF subunit (NFM), and the intermediate filament α-internexin (INT) at P4. At 5 months, NF-DP, NFM, and INT remained significantly lower in knockouts. At 12 months, NF-P was again significantly decreased, and INT significantly increased, in KOs compared with wild type. In addition, protein levels of class III neuron-specific ß-tubulin and microtubule-associated protein 2 were significantly increased in NFL KO mice at P4, 5 months, and 12 months, whereas ß-actin levels were significantly decreased at P4. Immunocytochemical studies demonstrated that NF-DP accumulated abnormally in the perikarya of cortical neurons by 5 months of age in NFL KO mice. Neurons that lacked NF triplet proteins, such as calretinin-immunolabeled nonpyramidal cells, showed no alterations in density or cytoarchitectural distribution in NFL KO mice at 5 months relative to WT mice, although calretinin protein levels were decreased significantly after 12 months in NFL KO mice. These findings suggest that a lack of NFL protein alters the expression of cytoskeletal proteins and disrupts other NF subunits, causing intracellular aggregation but not gross structural changes in cortical neurons or cytoarchitecture. The data also indicate that changes in expression of other cytoskeletal proteins may compensate for decreased NFs.

Control of neuronal network organization by chemical surface functionalization of multi-walled carbon nanotube arrays.

Carbon nanotube substrates are promising candidates for biological applications and devices. Interfacing of these carbon nanotubes with neurons can be controlled by chemical modifications. In this study, we investigated how chemical surface functionalization of multi-walled carbon nanotube arrays (MWNT-A) influences neuronal adhesion and network organization. Functionalization of MWNT-A dramatically modifies the length of neurite fascicles, cluster inter-connection success rate, and the percentage of neurites that escape from the clusters. We propose that chemical functionalization represents a method of choice for developing applications in which neuronal patterning on MWNT-A substrates is required.

Axonopathy and cytoskeletal disruption in degenerative diseases of the central nervous system.

There has been growing interest in the axon as the initial focus of pathological change in a number of neurodegenerative diseases of the central nervous system. This review concentrates on three major neurodegenerative conditions--amyotrophic lateral sclerosis, multiple sclerosis and Alzheimer's disease--with emphasis on key cellular changes that may underlie early axonal dysfunction and pathology and, potentially, the degeneration of neurons. In particular, this review will address recent data that indicate that the main pathological stimuli for these conditions, though often not definitively determined, result in an initial perturbation of the axon and its cytoskeleton, which then results in slow neuronal degeneration and loss of connectivity. The identification of a degenerative process initiated in the axon may provide new therapeutic targets for early intervention to inhibit the grim outcomes related to the progression of these diseases.