Carbon nanotubes for modulating neuronal chloride levels
The developmentally-programmed reduction of neuronal intracellular chloride levels is essential for proper neuronal functioning, particularly with respect to the inhibitory function of the neurotransmitter GABA. Dysregulation of this “chloride shift”, leading to abnormally elevated intracellular chloride levels, is associated with neurological disorders including epilepsy, psychosis, and Alzheimer’s disease, as well as neuronal injury in traumatic brain injury or cerebral ischemia / stroke. This technology provides for a novel formulation of carbon nanotubes (CNT) which, through direct contact with the neuron, are shown to reduce intraneuronal chloride levels to normal levels. This technology may therefore be useful as a novel therapeutic for the reduction of neuronal chloride levels in patients suffering from neurological disease.
This invention comprises electrically-conductive few-walled CNTs which may be incorporated in novel formulations of biocompatible carriers. Through a molecular mechanism defined by the inventors, neurons exposed to CNTs upregulate the KCC2 chloride transporter which directly reduces the levels of intracellular chloride. This capacity was demonstrated in both primary cultures of rat cortical neurons, as well as in rat cortical brain slice cultures. The mechanism appears to be unique to CNT, and is not duplicated by other nanomaterials, such as silicon dioxide nanowires or a gold matrix. Through incorporation into biocompatible materials, these CNTs may be used in as biological implants to therapeutically reduce neuronal chloride levels in patients with neurological disease. Furthermore, these materials may be formulated as kits, enabling their broad distribution and use for both medical and research applications.
- Method and kit for increasing KCC2 expression and reducing chloride levels in cultured neurons
- Accelerating differentiation / maturation of neurons in cell culture
Most chronic neurological conditions such as epilepsy are treated using oral medications, which can be effective but often result in side effects due to broad drug activity in the brain. As an implant, this technology enables targeting of specific brain regions which could allow effective treatment of these conditions while reducing non-specific effects of medication.
Duke File (IDF) Number
- Liedtke, Wolfgang
- Liu, Jie
For more information please contact
- Gopalakrishnan, Karthik