Forming the academic and biological interface between neuroscience and engineering
Jessica Colby-Milley
B@M: February 19th, 2013
Following the neuroengineering workshop held in London in March 2012, leading researchers from McGill and Imperial College London re-united at the Neuro on January 25th, 2013 to promote and facilitate further collaborations in neurotechnology research between the two Universities.
The workshop showcased the innovative, cross-disciplinary research being conducted both at McGill and at Imperial College London, applying technologies such as surface engineering for the control of cell growth, hydrogel nanoparticle delivery systems and optogenetics. The presentations, 18 in all, delivered exciting applications of such technologies to further our current understanding of the nervous system as well as applications for the study and treatment of diseases such as Multiple Sclerosis and Parkinson’s disease.
Dr. Rose Goldstein makes global remarks that frame the workshop as a symbol of McGill's vision to support international collaborations that bring tangible results on the frontiers of neuroscience research.
Professor Richard Reynolds (Imperial College London) talks on grey matter atrophy in Multiple Sclerosis
Research from the laboratory of leading Multiple sclerosis (MS) investigator, Professor Richard Reynolds, has helped identify mechanisms that may contribute to grey matter atrophy in MS. Although readily associated with its characteristic white matter lesions, grey matter loss in MS plays a key role in the progression of clinical deficits. Interestingly, it is this grey matter atrophy, rather than white matter lesions, which shows the best correlate with the rate of cognitive decline in MS. Professor Reynolds and colleagues have demonstrated the existence of a compartmentalized immune response within the meninges entering the sulci of the brain that may contribute to such grey matter loss. This response is thought to originate from the initial influx of activated peripheral immune cells into the central nervous system, which can then form lymphoid follicle-like structures in the sub-arachnoid space within the brain sulci. The accumulation of immune cells in these regions results in the brain being bathed in a persisting inflammatory milieu whereby inflammatory mediators may diffuse into the underlying cortex causing damage.
Grey matter atrophy and the accumulation of cortical lesions
To further investigate the compartmentalized meningeal inflammation in MS, Professor Reynolds and colleagues have been developing a chronic rat MS model, to mimic both the demyelination and meningeal inflammation observed in human MS cases. Through the use of collagen hydrogels, lentiviral vectors expressing pro-inflammatory molecules are delivered to the subarachnoid space of the rat brain. The benefits of this novel biomaterial delivery system are plentiful. Collagen hydrogels are biocompatible intelligent carrier systems and their specific properties such as delivery rate and surface recognition can be tailored and controlled. Furthermore, in the rat MS model described by professor Reynolds, injection of collagen hydrogels into the subarachnoid space produces a network of collagen fibrils permitting the flow of cerebral spinal fluid (CSF), whereas injection of lentiviral nanoshells alone resulted in clustering and an interruption of CSF flow.
- strong expression maintained up to 3 months.
- tranduction occurs in a large proportion of pial epithelial cells and subpial astrocytes.
The use of biomaterials for the targeted delivery of immunomodulatory molecules holds promising potential beyond the development of animal models. As highlighted by Professor Reynolds, this technology could be utilized for the delivery of targeted immunomodulatory therapy not only in in MS but also for neurodegenerative diseases with a strong inflammatory component such as Alzheimer’s disease (AD). To this effect, a European Union consortium has been developed to test epicortical delivery systems for the development of both animal models and therapeutic approaches for MS and AD. Although a lot of work is still required to ensure the safety of such biomaterial-based delivery systems in humans, they offer a flexible therapeutic option that could be applicable to many different neurodegenerative diseases.
in the photo
front row: (left to right) Veronique Laforte, Dr. Stefano Stifani, Dr. Richard Reynolds, Dr. Rose Goldstein, Dr. Claudio Cuello, Dr. Holger Krapp
middle row: Dr. Abbas Sadikot, Dr. Jane Saffell, Dr. Simon Schultz, Dr. Tim Kennedy, Dr. David Dexter, Dr. Aldo Faisal, Dr. Edward Ruthazer
back row: Dr. Theo Zanos, Dr. David J. Sharp, Dr. Martyn Boutelle, Dr. Phil Barker, Dr. Fred Charron, Dr. Margaret Magdesian.
all photo credits: Owen Egan
McGill and ICL investigators pose together after Dr. Rose Goldstein (Vice-Principal, Research and International Relations) keynote. Workshop organizer, Dr. Stefano Stifano, and Brain@McGill chair, Dr. Claudio Cuello, also pictured here.
Dr. Abbas Sadikot (McGill) talks on the treatment of Parkinson’s disease through neurosurgery
Parkinson’s disease is a progressive neurodegenerative disorder that is deeply debilitating, posing challenges when attempting movements required for everyday living. In Parkinson’s disease, a loss of the dopaminergic cells in the substantia nigra pars compacta of the midbrain leads to hyperactivity in the output of the basal ganglia, putting an excessive break on the thalamocortical system and ultimately resulting in difficulties with movement. Patients can exhibit a resting tremor, rigidity, and a slow, hesitant gait, symptoms that can be regulated with medication. Unfortunately, these symptoms can eventually become unresponsive to this form of treatment. When this occurs, certain PD patients may be candidates for deep brain stimulation. In the approach performed by Dr. Sadikot, patients are implanted with a stimulator, consisting of platinum-iridium electrodes, implanted into basal ganglia nuclei such as the subthalamic nucleus. The stimulator is connected to an extension device and an impulse generator located subcutaneously in the chest wall. The therapeutic effects of deep brain stimulation on the improvement of movement in PD patients can be remarkable. In one case presented by Dr. Sadikot, a patient who, before surgery, exhibited significant rigidity and a very slow, hesitant gait, after surgery displayed a dramatic improvement in gait and movement. These effects were already apparent just a month after surgery, when the patient had just returned from a weekend of cross-country skiing. Furthermore, at the frequency used in PD patients, deep brain stimulation does not appear to cause any local damage. Many years after a thalamic stimulator is implanted, if turned off, will result in a return of the former tremor in a matter of seconds, demonstrating that the cells present in this area at the time of implantation are still functional.
The mechanisms by which deep brain stimulation produces such beneficial effects on movement in Parkinson’s disease patients are currently under investigation by Dr. Sadikot and colleagues. The effects of deep brain stimulation may involve inhibition of the hyperactivity occurring in areas of the basal ganglia. However, these effects are likely to extend beyond local neuronal cell bodies and include several elements such as glial cells in the environment surrounding the implanted electrodes. In relation to the precise localization of the electrodes, MRI scans alone do not reveal this information. In order to further investigate the localization of the electrodes, Dr. Sadikot in collaboration with Dr. Gilles Bertrand have developed a new 3D, voxel based atlas, which includes a segmentation of the different nuclei within the thalamus and subthalamic areas. This atlas can be combined with high resolution MRI scans and has revealed that many of the effective contacts made by the electrodes are not necessarily in the subthalamic nucleus but also dorsal to this area.Deep brain stimulation has provided significant relief for individuals suffering from PD. Nonetheless, there is still much to be understood about the neurobiological mechanisms underlying its effects. Deep brain stimulation also offers many interesting opportunities for integration of additional technologies. One possibility, described by Dr. Sadikot, could be the inclusion of implants responsive to the dynamic physiological state, creating a closed-end system.
The ongoing research both at McGill and Imperial College London, integrating the knowledge and techniques from the fields of neuroscience and engineering will undoubtedly play an integral role as we continue to uncover the mysteries of the nervous system in health and disease. The newly established partnership between the two universities will extend the scope of sub-fields, available technologies and opportunities to promote growth and advances in neuroengineering research.
Additional video for Prof. David T Dexter's (ICL) talk on neural disease and repair for Parkinson's is available here >