References:
- Dulin JN, Moore ML, Gates KW, Queen JH, Grill RJ. (2011) Spinal cord injury causes sustained disruption of the blood-testis barrier in the rat. PLoS One. 6(1): e16456.
- Pati, S, Khakoo, AY, Zhao, J, Jimenez, F, Gerber, M, Harting, MT, Redell, JB, Grill, RJ, Matsuo, Y, Guha, S, Cox, CS, Reitz, MS, Holcomb, JB, Dash, PK. (2011) Human mesenchymal stem cells inhibit vascular permeability by modulating VE-cadherin/beta-catenin signaling. Stem Cells Dev. 20, 89-101
- Bedi SS, Yang Q, Crook RJ, Du J, Wu Z, Fishman HM, Grill RJ, Carlton SM, Walters ET. (2010) Chronic spontaneous activity generated in the somata of primary nociceptors is associated with pain-related behavior after spinal cord injury. J Neurosci. 30, 14870-82.
- Dash, PK, Orsi, SA, Zhang, M, Grill, RJ, Pati, S, Zhao, J, Moore, AN. (2010) Valproate administered after traumatic brain injury provides neuroprotection and improves cognitive function in rats. PLoS One. 5:e11383.
- Herrera, JJ, Haywood-Watson, RJ, Grill, RJ. (2010) Acute and chronic deficits in the urinary bladder following spinal contusion injury in the adult rat. J Neurotrauma. 27, 423-31.
- Nesic, O, Guest, JD, Zivadinovic, D, Narayana, PA, Herrera, JJ, Grill, RJ, Mokkapati, VU, Gelman, BB, Lee, J. (2010) Aquaporins in spinal cord injury: the janus face of aquaporin 4. Neuroscience. 168, 1019-35. Epub 2010 Jan 28.
- Wang, Y, Zhao, J, Kalsotra, A, Turman, CM, Grill, RJ, Dash, PK, Strobel, HW. (2008) CYP4Fs expression in rat brain correlates with changes in LTB4 levels after traumatic brain injury. Journal of Neurotrauma, 25, 1187-94.
Raymond Grill, Ph.D.
Assistant Professor
UTHSC, Medical School, (713) 500-6132
Raymond.J.Grill@uth.tmc.edu
Spinal Cord Injury: Acute and Chronic Inflammation
Traumatic injury to the spinal cord initiates a biochemical hurricane that both destroys and alters tissues in such a manner that successful regeneration and repair are stunted, leaving the individual facing a lifetime of paralysis and neurosensory dysfunction. Inflammation is a broadly-used term that describes several of the biochemical processes elicited by spinal trauma. Injury-induced inflammatory mediators play a host of roles including immune activation, cellular protection and cytotoxicity, to name only a few. The role of inflammation has been described as that of a two-edged sword; acting to destroy and remove damaged cells and tissue, but also to initiate reparative healing. It is thought that the timing of inflammatory events determines outcome; for instance, early inflammation is necessary to activate the immune system for clearance of dead cells while late inflammation may drive such processes as glial scarring and neuronal hyperexcitability, leading to chronic neuropathic pain.
Our laboratory is interested in determining the pathological processes that shape outcome following spinal cord injury. While a great deal of scientific interest is focused on ways of preserving damaged spinal tissue in the early time period following injury, we have largely focused on what is referred to as the “chronic” phase of spinal cord injury which in humans can mean months-to-decades and in rodents (our chosen model) months out to a year from insult. It has been this time period that has been so refractory to regeneration and functional improvement. It has been assumed that the inflammatory process is a hallmark of only the acute phase of spinal cord injury. We have recently demonstrated, however, the presence of a profound inflammatory response involving elements of the arachidonic acid signaling pathway in the chronic phase of spinal cord injury. We are currently collaborating with other members of the CRB and the Department of Integrative Biology and Pharmacology to understand: 1) the mechanisms that continue to promote inflammation in the chronic phase of spinal cord injury and 2) the functional ramifications of such chronic inflammation, including both progressive glial hyper-reactivity and vascular dysfunction, and the establishment and maintenance of chronic neuropathic pain.
