The Therapeutic Potential of a Toll-Like Receptor 9 (TLR9) Antagonist in Spinal Cord Injury
The Effects of a TLR9 Antagonist in Astrocyte Function In Vitro and at the Glial Scar following SCI
This project investigates the effects of a TLR9 antagonist on astrocyte proliferation, migration, chemotactic properties and chondroitin proteoglycan production in vitro, and following a mid-thoracic spinal cord contusion injury.
Similar studies are also performed in genetically modified mice to determine whether astroglial function and glial scar formation are modified in TLR9 knockout mice compared to wild type controls.
Effects of a TLR9 Antagonist on Below-Level Neuropathic Pain Mechanisms: Focus on Glial Glutamate Transporters
This project is based on our earlier findings indicating that intrathecal administration of a TLR9 antagonist to mice sustaining a mid-thoracic SCI attenuates below-levelneuropathic pain (David, et.al.,2013). Current investigations are unraveling the effects of the TLR9 antagonist on mechanisms of pain processing in the dorsal horn of the lumbar spinal cord, with particular emphasis on glial glutamate transporters.
Neuronal Protection by a TLR9 Antagonist following SCI
This project is based on our earlier in vitro findings sowing that a TLR9 antagonist acts directly on neurons and protects them against glutamate-elicited neurotoxicity (Acioglu, et. al., 2016). Current investigations are determining whether apoptotic and autophagic death of neurons is attenuated at the injury epicenter following intrathecal administration of a TLR9 antagonist to mice sustaining a mid-thoracic injury.
Early Surgical Decompression for the Treatment of Acute Trauatic Spinal Cord Injury
This project is based on earlier findings (Jalan, et. al., 2016). It investigates the potential therapeutic benefits of surgical decompression of the spinal cord in order to prevent secondary injury and optimize neurological recovery. Motor, sensory and autonomic functions are assessed by a number of behavioral tests. Histological approaches are used to evaluate white matter sparing and lesion volume.
Role of Plasma Membrane Calcium ATPase2 (PMCA2) in Nociception, Neuropathic Pain and the Mechanisms of Pain Processing in the Dorsal Horn of the Spinal Cord
Role of PMCA2 in Modality- and Sex-Specific Pain and Pain Mechanisms
This project is based on our recent findings showing differential responsiveness to modality-specific pain stimuli in female, but not male, PMCA2 wild type versus heterozygous mice (Khariv, et. al., 2017). The investigations also identified female-specific changes in molecular pathways governing pain processing in the dorsal horn of the spinal cord. The current studies are determining the role of gonadal hormones and their spinal receptors in female-specific pain responses in these mice.
Role of PMCA2 in Neuropathic Pain in Animal Models of Multiple Sclerosis, Spinal Cord Injury and Peripheral Nerve Injury
This project investigates the involvement of PMCA2 in neuropathic pain experienced by mice affected by experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis and by spinal cord injury. The inflammatory triggers that modulate the expression and activity of this neuronal calcium extrusion pump are analyzed.