Dr. Raj Midha
Dr. Rajiv Midha M.D., M.Sc., F.R.C.S.(C)
Department of Clinical Neurosciences Faculty of Medicine Telephone: (403) 944-1259; e-mail: rajmidha@ucalgary.caRESEARCH INTERESTS
The Midha research lab investigates novel approaches to enhancing nerve regeneration and improving outcome after nerve injury. The research involves rodent models of nerve injury and regeneration, investigating the utility of synthetic nerve grafts, nerve transplantation, growth factors, cell adhesion molecules and stem cells. The lab holds ongoing collaborations with Drs. Zochodne, Webb, Toth, Syed and others at the university. The Midha lab also collaborates with several internationally recognized nerve regeneration labs outside of the University of Calgary, including Drs. Freda Miller and Molly Shoichet from the University of Toronto and Dr. Tessa Gordon from the University of Alberta.
GFP-labelled SKPs in an injured peripheral nerve
Major Projects
1. Repair of Nerve Injuries using Skin Derived Precursor Stem Cells
Cells derived from the dermis of skin (Skin-derived precursors, or SKPs) have been shown to generate both neural and mesodermal progeny given the appropriate growth conditions, suggesting their role as a novel multipotent adult stem cell that may provide an accessible, autologous source for transplantation therapies. We are currently exploring the ability of SKP-derived Schwann cells to survive and maintain their differentiation in the chronically denervated nerve and hope to ascertain their role in promoting nerve regeneration by examining SKP transplanted nerves using immunohistochemical, electrophysiological and behavioural assessment techniques.
2. Repair of Peripheral Nerve Injuries Through Delivery of in vivo Concentration Gradients of Soluble Nerve Growth Factor (NGF)
Previous research has examined the application of exogenous nerve growth factor (NGF) to the microenvironment of the injured peripheral nerve, attempting to produce a situation similar to that of target organ reinnervation. However, placement of NGF within the lumen of nerve guidance tubes has resulted in variable regenerative success, perhaps owing to poor bioavailability or a lack of delivery of concentration gradients of NGF, which are critical in in vitro studies. We have recently developed a novel in vivo model of administering daily concentration gradients of NGF by directly manipulating the placement of the catheter-nerve conduit junction and are exploring whether delivery of concentration gradients of NGF enhance both regenerative capacity and behavioural recovery following transection of the rat sciatic nerve. We are assessing this through the use of EMG measurements, gastrocnemius muscle weights, histomorphometry (axon/myelination counts), as well as skilled (ladder rung, tapered beam) and unskilled (ground reaction forces, quantitative kinematics) sensorimotor tasks.
3. Is the poor outcome of regeneration after peripheral nerve injury due to motor neuron death in mature animals?
Multiple peripheral nerve injuries often result in poor motor functional recovery, though there may be several factors which affect such results. Previous studies relating peripheral nerve axotomy to neuron survival have shown the effects of axotomy to be time dependent. Injuries occurring at birth inflict dramatic cell death and this susceptibility to cell death has been shown to be dependent on maturation of these neurons from an immature growth stage to a more stable transmitting stage. In this study, we investigated the survival of motor neurons after repeat injuries in mature rats using double labeling techniques. Results show that motoneuron cell death is insignificant after chronic and or sequential nerve injury in adults, yet only 50% of motoneurons are capable of exhibiting a regenerative response after chronic and sequential nerve injury. The poor outcomes of regeneration may thus be due to (1) losing ability of regeneration in some motor neurons in spite of their survival after multiple injuries or (2) blocking of new axons at repair site or(3) losing enough support of neurotrophy from distal stump.
CURRENT RESEARCH SUPPORT
David Kline Research Award, AANS/CNS Joint Section on Disorders of the Spine and Peripheral Nerve. Title: The capability of skin derived stem cells to promote nerve regeneration, through Schwann cell differentiation. Midha R, Magaldi M, 2006-2007
CIHR Regerative Medicine and Nanomedicine Initiative. Title: Dynamic manipulation of nerve regeneration: an electronic-axon interface. Zochodne D, Midha R, Jullien G, Syed NI, Verge VMK, Gordon T, Chan KM., 2007-2012
CIHR. Title: Repair of nerve injuries using skin derived precursor cells. Midha R, Gordon T., 2007-2010
PERSONNEL
Postdoctoral Fellow: Dr. Qing Gui Xu
Graduate Students: Stephen Kemp, Sarah Walsh
Technician: Joanne Forden
Summer student: Shahbaz Syed