Spinal Cord Injury Research

Spinal cord injury (SCI) is a debilitating condition that affects motor, sensory and autonomic functions. Neuroinflammation and glial activation are among hallmarks of SCI and contribute to both damage and repair. Innate immune receptors are essential drivers of neuroinflammation. Toll-like receptors (TLRs) are one of the best characterized innate immune receptors. Following SCI, binding of endogenous ligands released by injured or dying cells initiates TLR signaling leading to cytokine release which triggers neuroinflammation. TLRs are expressed in immune cells that invade the injury site as well as glia and neurons of the spinal cord. Different members of the TLR family have been studied in the context of SCI as potential therapeutic targets to modulate neuroinflammation and to foster an environment that promotes repair.

Our research has focused on the contribution of TLRs to spinal cord injury. Our studies investigated

• The effects of intrathecal TLR9 agonist and antagonist on functional deficits following SCI.
• TLR9 as a therapeutic target to prevent neuropathic pain, a co-morbidity associated with SCI.
• The modulation of astrocyte function by TLR9 at the glial scar following SCI
• The role of TLR9 in astrocyte-macrophage interactions
• The contribution of TLR9 to the polarization of macrophages into beneficial or detrimental phenotypes in the injured spinal cord
• Role of neuronal TLR9 in cell survival and astrocyte-neuron interactions.

The investigations utilize mouse models of spinal cord contusion injury, genetically modified mice, spinal cord neuronal and glial cultures and co-cultures, molecular and cellular approaches and behavioral assays to study neuroimmune interactions, the crosstalk between neurons and glia, mechanisms of neuronal protection and degeneration, axonal protection, functional recovery and alleviation of co-morbidities including neuropathic pain.