Faculty Book
JOHN R. BETHEA, Ph.D.
Associate Professor, Department of Neurological Surgery
Immunological consequences of spinal cord injury and
the development of neuroprotective strategies
Research
Interests
In my laboratory we are studying acute spinal cord injury to try to understand the cellular and molecular mechanisms that contribute to secondary neuronal cell death. To this end, my laboratory has two main research objectives. First, we are studying the neuro-inflammatory response that occurs following spinal cord injury (SCI) because we believe that inflammation is a central mediator of secondary neuronal injury. We are also looking for novel regulators of neuro-inflammation.
To determine what role(s) trauma-induced inflammation plays in mediating secondary neuronal injury and cell death following SCI, we use transgenic mouse models and other molecular biological approaches. We have recently demonstrated that traumatic SCI initiates a very robust inflammatory response, both within the spinal cord and systemically. Specifically, we have shown that traumatic SCI activates NF-kB within macrophages, microglia, endothelial cells and neurons. NF-kB is a transcription factor that plays a pivotal role in regulating inflammation, and possibly apoptotic cell death pathways. We have recently generated mice that do not express functionally active NF-kB in neurons and astrocytes and are currently studying spinal cord injury in mice.
The second major focus of my laboratory is to develop neuroprotective strategies for the treatment of acute SCI. To this end, we have begun investigating what effects the potent anti-inflammatory cytokine IL-10 has on trauma induced inflammation and the subsequent neuropathology of SCI. Our studies have demonstrated that systemic treatment with IL-10 after SCI significantly reduces trauma induces inflammation within the spinal cord and systemically. Furthermore, we have also demonstrated that IL-10 immunotherapy significantly reduces SCI induced neuropathology and the resulting secondary neuronal necrosis. The ultimate goal of the research in my laboratory is to develop effective therapeutic strategies for the treatment of SCI. We are also investigating pharmacological inhibition of pathways that are involved in secondary injury with the ultimate goal of developing new neuroprotective and regenerative strategies for SCI.
Video Introduction
Hu WH, Mo XM, Walters WM, Brambilla R, Bethea JR. TNAP, a novel repressor of NF-kappa B-inducing kinase, suppresses NF-kappa B activation.J Biol Chem. 2004 Jun 18 [Abstract]
Hu W-H, Walters WM, Xia X-M, Karmally SA, Bethea JR (2003) Neuronal glutamate transporter EAAT4 is expressed in astrocytes. Glia 44:13-25.
Hu W-H, Hausmann ON, Yan M-S, Walters WM, Wong PKY, Bethea JR (2002) Identification and characterization of a novel Nogo-interacting mitochondrial protein (NIMP). J Neurochem 81:36-45.
Bethea JR, Dietrich WD (2002) Targeting the host inflammatory response in traumatic spinal cord injury. Curr Opin Neurol 15:355-360.
Hausmann ON, Hu W-H, Keren-Raifman T, Witherow DS,Wang Q, Levay K, Frydel B, Slepak VZ, Bethea JR (2002) Spinal cord injury induces expression of RGS7 in microglia/macrophages in rats. Eur J Neurosci 15:602-612.
Bethea JR, Nagashima H, Acosta MC, Briceno C, Gomez F, Marcillo AE, Loor K, Green J, Dietrich WD (1999) Systemically administered interleukin-10 reduces tumor necrosis factor-alpha production and significantly improves functional recovery following traumatic spinal cord injury in rats. J Neurotrauma 16:851-863.
Bethea JR, Castro M, Keane RW, Lee TT, Dietrich WD, Yezierski RP (1998) Traumatic spinal cord injury induces nuclear factor-kB activation. J Neurosci 18:3251-3260.
Last updated: July 26, 2004
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