CALCIUM BLOCKER & RELATED THERAPY FOR CEREBRAL ISCHEMIA

Summary

Principal Investigator: James Grotta
Affiliation: Texas Medical Center
Country: USA
Abstract: DESCRIPTION (Adapted from the applicant's abstract): This research proposal is a re-submission of a research project that was submitted as a competitive renewal. The long-term objective of this research proposal is to evaluate and understand potential pharmacotherapies for acute cerebral ischemia so that appropriate drugs might be tested which will reduce or prevent calcium entry into neurons or its consequences. Therapies that will be directed at this will include selected calcium channel blockers, competitive and non-competitive glutamate antagonists, phospholipase antagonists, and possibly newer agents which may act on glycine or sigma sites. Outcome measures will include mortality, light microscopic measurement of ischemic damage, and learning ability. Mechanisms of action of each pharmacotherapy will be determined by cerebral blood flow, immunocytochemical localization and quantitation of calcium calmodulin binding and assessment of CaM-kinase II activity. The second major goal of this research is to expand previous studies of calcium calmodulin binding after global ischemia to better understand calcium activated events in determining irreversible neuronal injury. Studies will be designed to correlate calcium calmodulin binding studies with CaM Kinase II activity and explore the behavior of this kinase after various ischemic intervals.
Funding Period: 1987-07-01 - 1994-12-31
more information: NIH RePORT

Top Publications

  1. ncbi Combining insulin-like growth factor derivatives plus caffeinol produces robust neuroprotection after stroke in rats
    Xiurong Zhao
    Vascular Neurology Program, Department of Neurology, University of Texas-Houston Medical School, Houston, Tex 77030, USA
    Stroke 36:129-34. 2005
  2. ncbi Using behavioral measurement to assess tumor progression and functional outcome after antiangiogenic treatment in mouse glioma models
    Hongyan Yang
    Institute for Neuroscience, Department of Psychology, University of Texas at Austin, Austin, TX 78712, USA
    Behav Brain Res 182:42-50. 2007
  3. ncbi Local fluorouracil chemotherapy interferes with neural and behavioral recovery after brain tumor-like mass compression
    Hongyan Yang
    Institute for Neuroscience, University of Texas at Austin, 1 University Station, Austin, TX 78712, USA
    Behav Brain Res 172:80-9. 2006
  4. ncbi Mass-related traumatic tissue displacement and behavior: a screen for treatments that reduce [corrected] harm to bystander cells and recovery of function
    Hongyan Yang
    Institute for Neuroscience and Department of Psychology, University of Texas at Austin, Austin, Texas 78712, USA
    J Neurotrauma 23:721-32. 2006
  5. ncbi Interruption of functional recovery by the NMDA glutamate antagonist MK801 after compression of the sensorimotor cortex: implications for treatment of tumors or other mass-related brain injuries
    Hongyan Yang
    Institute for Neuroscience and Department of Psychology, University of Texas at Austin, 1 University Station, A8000, Austin, TX 78712, USA
    Exp Neurol 200:262-6. 2006
  6. ncbi A simple modification of the water maze test to enhance daily detection of spatial memory in rats and mice
    Se Hoon Choi
    Institute for Neuroscience, The University of Texas at Austin, Austin, TX 78712, USA
    J Neurosci Methods 156:182-93. 2006
  7. ncbi Wheel-running modestly promotes functional recovery after a unilateral cortical lesion in rats
    Xiurong Zhao
    Department of Neurology, University of Texas, Medical School, Houston, TX 77030, USA
    Behav Neurol 16:41-9. 2005
  8. ncbi Testing forelimb placing "across the midline" reveals distinct, lesion-dependent patterns of recovery in rats
    Martin T Woodlee
    Institute for Neuroscience, The University of Texas at Austin, Austin, TX 78712, USA
    Exp Neurol 191:310-7. 2005
  9. ncbi An intermittent, controlled-rate, slow progressive degeneration model of Parkinson's disease: antiparkinson effects of Sinemet and protective effects of methylphenidate
    Sheila M Fleming
    Department of Psychology, Institute for Neuroscience, University of Texas, Austin, TX 78712, USA
    Behav Brain Res 156:201-13. 2005
  10. ncbi Sensorimotor deficits associated with brain tumor progression and tumor-induced brain plasticity mechanisms
    Hongyan Yang
    Institute for Neuroscience and Department of Psychology, University of Texas at Austin, 1 University Station, A8000, Austin, TX 78712, USA
    Exp Neurol 207:357-67. 2007

Scientific Experts

  • Hongyan Yang
  • Sheila M Fleming
  • Xiurong Zhao
  • Timothy Schallert
  • Martin T Woodlee
  • Shi-Jie Liu
  • Se Hoon Choi
  • James C Grotta
  • Roger Strong
  • Jie Zhang
  • John J Hong
  • Jarek Aronowski
  • Zhi-Shuo Ou
  • Jaroslaw Aronowski
  • Theresa A Jones
  • Theresa Nguyen

Detail Information

Publications10

  1. ncbi Combining insulin-like growth factor derivatives plus caffeinol produces robust neuroprotection after stroke in rats
    Xiurong Zhao
    Vascular Neurology Program, Department of Neurology, University of Texas-Houston Medical School, Houston, Tex 77030, USA
    Stroke 36:129-34. 2005
    ..Further study of this combination appears justified...
  2. ncbi Using behavioral measurement to assess tumor progression and functional outcome after antiangiogenic treatment in mouse glioma models
    Hongyan Yang
    Institute for Neuroscience, Department of Psychology, University of Texas at Austin, Austin, TX 78712, USA
    Behav Brain Res 182:42-50. 2007
    ....
  3. ncbi Local fluorouracil chemotherapy interferes with neural and behavioral recovery after brain tumor-like mass compression
    Hongyan Yang
    Institute for Neuroscience, University of Texas at Austin, 1 University Station, Austin, TX 78712, USA
    Behav Brain Res 172:80-9. 2006
    ....
  4. ncbi Mass-related traumatic tissue displacement and behavior: a screen for treatments that reduce [corrected] harm to bystander cells and recovery of function
    Hongyan Yang
    Institute for Neuroscience and Department of Psychology, University of Texas at Austin, Austin, Texas 78712, USA
    J Neurotrauma 23:721-32. 2006
    ..This model may permit development of treatment strategies to alleviate brain mass effects, without disrupting neuroplasticity...
  5. ncbi Interruption of functional recovery by the NMDA glutamate antagonist MK801 after compression of the sensorimotor cortex: implications for treatment of tumors or other mass-related brain injuries
    Hongyan Yang
    Institute for Neuroscience and Department of Psychology, University of Texas at Austin, 1 University Station, A8000, Austin, TX 78712, USA
    Exp Neurol 200:262-6. 2006
    ..It may be possible to use this model to develop interventions that maintain anti-cancer effects but with diminished harm to bystander tissue and brain plasticity...
  6. ncbi A simple modification of the water maze test to enhance daily detection of spatial memory in rats and mice
    Se Hoon Choi
    Institute for Neuroscience, The University of Texas at Austin, Austin, TX 78712, USA
    J Neurosci Methods 156:182-93. 2006
    ..In this way one can assess whether the rodent is continuing to search in the older platform location (i.e., displaying a strategy-switching problem) or whether it has successfully adopted a new search strategy...
  7. ncbi Wheel-running modestly promotes functional recovery after a unilateral cortical lesion in rats
    Xiurong Zhao
    Department of Neurology, University of Texas, Medical School, Houston, TX 77030, USA
    Behav Neurol 16:41-9. 2005
    ..These results were in accordance with a marker linked to synaptogenesis. CONCLUSION: Wheel-running starting 3 days, but not 1 day, after an NMDA lesion is associated with improved functional recovery...
  8. ncbi Testing forelimb placing "across the midline" reveals distinct, lesion-dependent patterns of recovery in rats
    Martin T Woodlee
    Institute for Neuroscience, The University of Texas at Austin, Austin, TX 78712, USA
    Exp Neurol 191:310-7. 2005
    ..Unlike other tests, cross-midline placing methods can readily distinguish between severe stroke and severe parkinsonism in rats...
  9. ncbi An intermittent, controlled-rate, slow progressive degeneration model of Parkinson's disease: antiparkinson effects of Sinemet and protective effects of methylphenidate
    Sheila M Fleming
    Department of Psychology, Institute for Neuroscience, University of Texas, Austin, TX 78712, USA
    Behav Brain Res 156:201-13. 2005
    ..These data suggest that establishing a symptomatic threshold preclinically may help researchers evaluate potential treatments and model individual and group resistance to nigrostriatal insults...
  10. ncbi Sensorimotor deficits associated with brain tumor progression and tumor-induced brain plasticity mechanisms
    Hongyan Yang
    Institute for Neuroscience and Department of Psychology, University of Texas at Austin, 1 University Station, A8000, Austin, TX 78712, USA
    Exp Neurol 207:357-67. 2007
    ....