The goal of the Reynolds Family Spine Laboratory is to discover new therapeutic targets to improve the functional outcomes of chronic and acute spinal cord injury (SCI) and Multiple Sclerosis (MS). The current research uses animal models of SCI and MS, genetically modified mice, and neuronal and glial cultures/co-cultures in order to investigate the crosstalk between neurons, glia, and immune cells. The cellular and molecular mechanisms underlying neuroprotection, preservation of injured axons, and axonal regeneration are analyzed. Our objective is to improve the balance between the beneficial and detrimental effects of neuroinflammation and glial activation in order to reduce secondary injury and ameliorate functional recovery, including restoration of motor function and alleviation of neuropathic pain.
The laboratory investigates
- the role of innate immune receptors in the modulation of neuroinflammation, glial activation, glial scar function, and axonal preservation/regrowth following SCI. Ongoing studies focus on toll-like receptors (TLRs) in the resident central nervous system (CNS) cells. Intrathecal treatment with TLR agonists and antagonists is used to create a permissive environment at the injury epicenter that fosters cell survival and axonal regeneration.
- the modulation of astrocyte function, astrocyte-neuron, and astrocyte-macrophage interactions by TLRs, in vitro, and in vivo.
- the role of neuronal TLRs in neuroprotection and neurite outgrowth, in vitro.
- mechanisms of neuropathic pain in SCI and MS. Neuropathic pain is a debilitating condition that is not adequately alleviated by currently available therapies. Therefore, the discovery of novel therapeutic targets is urgently needed. We found that a reduction in plasma membrane calcium ATPase 2 (PMCA2), an essential neuronal calcium pump, contributes to neuropathic pain mechanisms in the dorsal horn of the spinal cord in animal models of SCI and MS, and in genetically modified mice. Ongoing investigations are assessing whether intrathecal gene delivery to restore PMCA2 levels in the spinal cord alleviates neuropathic pain in animal models of SCI and MS.