Strauss Laboratory Research Topics
Eicosanoid changes in the brain
Human and Animal Brain Injury Studies
We are investigating the association of dynamic post-injury brain eicosanoid changes with differential cytochrome P450 (CYP) gene expression in order to determine the source of these bioactivities. Histologic, biochemical, cell signalling, genomic, and epigenetic responses to manipulations of these eicosanoids and their metabolic enzymes are being studied.
Pharmacologic, viral-mediated, and genetic approaches to manipulating brain eicosanoid formation are being employed to study altered recovery of cognitive and motor function after TBI in rodent models.
In addition, we collect injured brain tissue, cerebral spinal fluid, and blood specimens from TBI patients for eicosanoid analysesusing a pico-sensitive liquid chromatography – mass spectrometry method, as well as genomic and proteomic analyses of altered inflammatory and cell death mediators.
Recently, in collaboration with neurosurgeon Kost Elisevich, M.D., co-director of Clinical Neurosciences at Spectrum Health System in Grand Rapids, we are investigating altered eicosanoid and neuroinflammatory mediator levels in patients with chronic, treatment-resistant epilepsy. We are currently seeking funding to expand these human studies.
Preclinical testing of eicosanoid analogs and novel compounds that block degradation of P450 eicosanoids has been performed in collaborations with Prof. John Falck (UT Southwestern), and Prof. Bruce Hammock (UC Davis). This strategy aims to prolong the elevation of potentially beneficial eicosanoids formed in the brain after TBI, improving the adaptive responses of the brain to injury. Behavioral and biochemical analyses are underway, to be followed by histopathological and molecular analyses that will characterize and identify the mechanisms of neuroprotection afforded by these agents.
Rational Combination Therapy
Currently, antiinflammatory drugs are used alone and somewhat speciously after TBI. We have initiated a study of rational combination treatments after TBI to improve the brain’s energy supply, reduce the formation of harmful reactive oxygen free radicals, and create an antiinflammatory environment that improves functional recovery. Further development of these combinations for clinical trials in TBI require a better understanding of their specificmechanisms, therapeutic windows and optimal dosing regimens for maximal efficacy. Several grant proposals have been submitted for funding through NIH and BioPharma companies to further support these studies.
- Animal Studies: Lab animal survival surgeries (rats and mice), CNS injury models (trauma, ischemia), behavioral recovery paradigms, in vivo antisense, in vivo microdialysis, development and validation of new methods.
- Pharmacology: Neuropharmacology, Drug pharmacokinetics: formulation, route of administration, blood and CNS levels, Pharmacodynamics: mechanisms of action and bioavailability, Behavioral pharmacology: hormones, neuroprotective and antiviral drugs.
- Molecular Biology: Cloning, promoter analyses, mutagenesis, transgenic mice genetic engineering, DNA:Protein interactions, transcription factor binding analyses, one- and two-dimensional electrophoretic separations and analyses, immunoblotting, development and validation of new methods.
- Quantitative & Analytical Chemistry: Assay development and validation, protein and lipid biochemistry, nucleic acids biochemistry, protein structure-function analyses, column chromatography, liquid chromatography, mass spectrometry, development and validation of new methods.
- Cell Biology: Brain histopathology, immunohistochemistry (neural & inflammatory markers), microscopy (fluorescence colocalization, light & dark field), primary cell culture (neural, immune), subcellular fractionation, cellular and molecular responses to viral infection.
- Strauss, K.I. and Jacobowitz, D.M. 1993. Quantitative measurement of calretinin and ßactin mRNA in rat brain micropunches without prior isolation of RNA. Mol. Brain Res., 20:229-239.
- Strauss, K. I., Kuznicki, J., Winsky, L., Kawagoe, J-I., Hammer, M. and Jacobowitz, D.M. 1997. The mouse calretinin gene promoter region: structural and functional components. Mol. Brain Res., 49:175-187.
- Strauss K.I., Barbe, M.F., Marshall R., Raghupathi, R., Mehta S., and Narayan, R.K. 2000. Prolonged cyclooxygenase-2 induction following traumatic brain injury in the rat. J. Neurotrauma 17:695-711.
- Strauss K.I. and Marini A.M. 2002. Cyclooxygenase-2 inhibition protects cultured cerebellar granule neurons from glutamate-mediated cell death. J. Neurotrauma 19:627-638.
- Narayan, R.K., Michel M.E., Strauss, K.I. and the Clinical Trials in Head Injury Study Group. 2002. Clinical Trials in Head Injury. J. Neurotrauma 19:503-558.
- Malik A.S., Narayan R.K., Cole R.W., Schwartz A.G., Pashko L.L., Strauss K.I. 2003. A novel dehydroepiandrosterone analog improves functional recovery in a rat traumatic brain injury model. J. Neurotrauma 20:463-475.
- Gopez, J.J., Yue H., Vasudevan, R., Malik, A.S., Fogelsanger, L.N., Lewis S., Panikashvili, D., Shohami, E., Jansen S.A., Narayan, R.K., Strauss, K.I. 2005. A Cyclooxygenase-2 Specific Inhibitor provides neuroprotection, reduces inflammation, and improves behavioral outcomes after traumatic brain injury. Neurosurgery 56: 590-604.
- Yue H., Strauss K.I., Borenstein M.R., Barbe M.F., Rossi L.J., Jansen S.A. 2004. Determination of bioactive eicosanoids in brain tissue by a sensitive reversed-phase liquid chromatographic method with fluorescence detection. J. Chromatography B 803:267-77.
- Strauss K.I. 2008. Antiinflammatory and neuroprotective actions of COX2 inhibitors in the injured brain. Brain Behav Immun. 22:285-98.
- Combined age- and trauma-related proteomic changes in rat neocortex: a basis for brain vulnerability. Mehan ND, Strauss K.I. Neurobiol Aging. 2012 Sep;33(9):1857-73. Epub 2011 Nov 16. doi: 10.1016/j.neurobiolaging.2011.09.029.
- Altered behavioral phenotypes in soluble epoxide hydrolase knockout mice: Effects of traumatic brain injury. Strauss KI, Gruzdev A, Zeldin DC. Prostaglandins Other Lipid Mediat. 2012 Aug 16. doi: 10.1016/j.prostaglandins.2012.07.005
- Temporal changes of cytochrome P450 (Cyp) and eicosanoid-related gene expression in the rat brain after traumatic brain injury. Matthew Birnie, Ryan Morrison, Ramatoulie Camara and Kenneth I Strauss. BMC Genomics. 2013.