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Regeneration and Repair in the Nervous System

This research focuses on the functional and structural repair of the damaged nervous system. Interdisciplinary teams are studying how neurons recover and regenerate from inquiry and trauma. These studies may have significant impact on therapeutic treatment of brain traumas from stroke and spinal injury as well as veterans suffering from physical trauma returning from war.
 
Regeneration and Repair in the Nervous System projects:

Thirty-two applications were received.  Five awards have been given to date.
 
Non-invasive cerbellar stimulation
The goal of this work is to understand whether non-invasive stimulation of the cerebellum can improve human motor performance and motor learning.  In this project, we use transcranial direct current stimulation, which is a painless and non-invasive way of stimulating the brain with very small currents.  We assess the effects of this brain stimulation as people learn new walking patterns on a custom split-belt treadmill or learn new reaching patterns in a robotic device.  It is our goal to understand if  brain stimulation can be used to improve motor function, and ultimately be applied to patients with damage to the brain.
Pablo Celnik and Amy Bastian; Departments of Physical Medicine & Rehabilitation, Neuroscience, and Kennedy Krieger Institute
 
Imaging regenerating and sprouting axons in the intact, living mammalian brain: An experimental platform for testing therapies to promote brain repair
The goal of this project is to image live regenerating and sprouting axons in the brains of intact adult mice to illuminate aspects of functional recovery from neural injury including traumatic brain injury and stroke.  Using 2 photon imaging, we can image axonal fine structure including individual synaptic varicosities, filopodia and cargo packets in the cerebral cortex and cerebellum of the intact adult anesthetized mouse and can do so repeatedly over many days or weeks.  We have realized that this preparation is ideal for addressing a fascinating and clinically important problem: axonal regeneration in the adult brain.  To date, the study of brain axon regeneration has relied upon dynamic imaging of either perturbed model systems (cultures, explants) or intact non-mammalian models (zebrafish, frogs) or analysis of fixed tissue from intact mammalian preparations, which yields only snapshots.  Our imaging technique allows for time-lapse imaging of regenerating and sprouting axons in the intact, adult mouse or rat brain, constituting an ideal test bed for therapies to promotes axonal regeneration in the brain.
David Linden, Joseph Steiner, Alex Kolodkin, and Ron Schnaar; Departments of Neuroscience, Neurology, Pharmacology & Molecular Sciences
 
Epigenetic regulation in axon regeneration
Growth arrest DNA damage-inducible gene 45 (Gadd45) encodes a family of proteins that have recently been shown to be involved in epigenetic DNA demethylation.  Taken advantages of the complementary expertise from team members, we will profile preconditioning-induced changes in DNA methylation landscape in DRG neurons at the genomic level and will investigate the role of GADD45a-dependent epigenetic changes in mediating the preconditioning effect in axon regeneration.
Guo-li Ming, Hongjun Song, Ahmet Hoke, and Fengquan Zhou; Departments of Neurology and Orthopaedic Surgery
 
The involvement of developmental pathways in motor neuron regeneration
A major factor that prevents functional recovery after peripheral nerve injury is the slow regenerative capacity of axons, which fail to reach distant targets prior to the establishment of inhibitory environments for reinnervation.  We hypothesize that developmental programs that regulate axonal extension and outgrowth may be useful tools to increase the regenerative power of injured neurons. We are currently using established in vivo and in vitro models of regeneration to test the utility of embryonic factors in promoting axonal regeneration.
Shanthini Sockanathan, Ahmet Hoke, and Thomas Brushart; Departments of Neuroscience, Neurology, and Orthopaedic Surgery
 
Human induced pluripotent stem cell (hiPSC) platform
We have fully established the technology to generate pluripotent human stem cells from patient skin biopsies.  So far we have established a number of induced pluripotent stem cell lines from patients with neurological disorders, including ALS, Huntington’s disease and trisomies.
Hongjun Song, Ted M. Dawson, and Guo-li Ming; Department of Neurology