In collaboration with Dr. Obenaus (Director, Non-Invasive Imaging Laboratory at Loma Linda University Medical Center -LLUMC), Dr. Currás-Collazo has used cortical contusion impact (CCI) and fluid percussion impact (FPI) protocols to show that diffusion weighted imaging (DWI) and T2 measures can distinguish between both injury models. Thus, MRI can be used to predict evolution of traumatic brain injury non-invasively (Fig. 1). Mild and severe degrees of CCI can also be distinguished using MRI and immunohistochemical techniques (in preparation). These studies were funded through an UC Neurotrauma Training grant (Obenaus et al, in press). Our next step is to use mild CCI (common TBI scenario in humans) to injure postnatal rats and measure MRI and MRS, histopathological and neurologic outcomes of injury. We will then examine the potential therapeutic value of transplanting human embryonic stem cells (hESCs) into the brains of these injured animals in collaboration with LLU (Drs. Obenaus, Ashwal, Hartman)
3Dr. Currás-Collazo recently completed a stem cell biology training course provided by UCI using CIRM funding. hESCs from H1 and H7 lines (WiCell) were cultured on both Matrigel and mouse embryonic fibroblasts (MEFs) at the UCI Stem Cell Facility. Dr. Curras-Collazo maintained and expanded hESCs during the length of the 1 week course. Fig. 2 shows H7 hESCs cultured on MEFS and later fixed and stained with alkaline phosphatase, a stain for pluoripotent stem cells (Fig. 3). Other hESCs were scraped and transferred to chamber slides for 24 hr and later fixed and stained with the nuclear fluorescent stain DAPI (blue) and anti-TRA-1-81 antibody (red), which is specific for human germ and stem cells (Fig. 4). As part of an ongoing project the Obenaus lab at LLU (collaborators: Drs. Ashwal (LLU) and Synder (Burnham Institute)) have successfully implanted these iron-labeled neural stem cells (C17.2) into postnatal rats 72 h after hypoxia/ischemia injury (HII) using a Rice-Vannucci (RVM). Fig. 5 illustrates implantation and tracking of NSCs (red) in vivo in control and HII animals from MRI combined with 3D volumetric reconstructions for quantitative analysis. More recent findings suggest that these iron-labeled NSCs persist up to 54 weeks post injury (results at 21 weeks shown in Fig. 6).
Pak, C.W., Currás-Collazo, M.C. and R.B. Meeker (2001) Mechanism of excitotoxic resistance in supraoptic neurons may involve higher tolerance to calcium load. "Soc. Neurosci. Abstr". 27, Program #178.4.
Curras-Collazo, M.C., Patel, U., Hussein, M.O. 2002. Reduced susceptibility of rat magnocellular neuroendocrine nuclei to transient focal ischemia produced by middle cerebral artery occlusion. Experimental Neurology. Vol. 178(2): p.268-279.
Gillard, E.R., Leon-Olea, M., Mucio-Ramirez, S., Coburn, C.G., Sanchez-Islas, E., de Leon, A., Mussenden, H., Bauce, L.G., Pittman, Q.J., Curras-Collazo, M.C. 2006. A novel role for endogenous pituitary adenylate cyclase activating polypeptide (PACAP) in the magnocellular neuroendocrine system. Endocrinol. Vol. 147(2): p.791-803.
Obenaus, A., Galloway, N., Robbins, M., Blanco, G., Snissarenko, E., Gillard, E., Lee, S., Curras-Collazo, M.C. 2006. Multi-modal magnetic resonance imaging alterations in two rat models of mild neurotrauma. J. Neurotrauma. Vol. 24(7): p.1147-60.
Qiu, S., Curras-Collazo, M. 2006. Histopathological and molecular changes produced by hippocampalmicroinjection of domoic acid. Neurotoxicology and Teratology. Vol. 28: p.354-362.
Qiu, S., Wook Pak, C., Curras-Collazo, M. 2006. Sequential Involvement of Distinct Glutamate Receptors inDomoic Acid-Induced Neurotoxicity in Rat Mixed CorticalCultures: Effect of Multiple Dose/Duration Paradigms,Chronological Age, and Repeated Exposure. Toxicological Sciences. Vol. 89(1): p.243-256.
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