The Noble laboratory is focused on translational research in the field of neurotrauma. Our overarching long-term objective is to develop targeted therapeutics that will improve recovery after traumatic spinal cord and pediatric brain injuries. This research relies on cellular, molecular, and behavioral tools to identify key mechanisms underlying early cell injury that impair recovery processes in preclinical models of neurotrauma. This multifaceted approach has led to the discovery of new pharmacologic and stem-cell based therapeutics that ameliorate several key features of spinal cord injury; namely, bladder and locomotor dysfunction and central neuropathic pain.
Similar progress has been made in our studies of traumatic injury to the pediatric rodent brain. We have found that age at time of injury is predictive of recovery in brain injured rodents, with younger ages showing less resilience to the injury with more profound long-term deficits in cognition and sociability. These studies have led to the discovery of unique, age-dependent immune-based signatures that give rise to long-term cognitive deficits. Importantly, these deficits can be rescued by either genetic or pharmacologic approaches that target the early innate immune response.
Left Panel: Immunolocalization of PCP4 (a marker of Purkinje cells in the cerebellum) at 1 day after traumatic injury at postnatal day 21. Courtesy of Kaila Parker.
Middle Panel: Localization of blood vessels (green) in the injured spinal cord at 3 weeks after spinal cord injury. F480+macrophages (white arrows) are localized at the lesioned site (Trivedi et al, Experimental Neurology, 2016).
Right panel: In vivo 2-photon imaging of the developing brain after a mild closed head injury. Blood vessels (green), vascular tracer indicative of leakage (red), meningeal vessels (yellow, indicative of co-labeling with the vascular tracer). Courtesy of Michael Donovan.