HYPOXIC/AGLYCEMIC STRESS TO ENDOTHELIAL CELLS OF THE BLO

Project: Research project

Description

Understanding BBB stroke pathophysiology is critical since stroke is a leading cause of death and disability and increased cerebrovascular permeability is an important factor for the development of ischemic brain damage and edema formation. Vasogenic brain edema, due to a BBB opening is the type of edema that is present in the brain after injury induced by a cerebrovascular accident. Vasogenic brain edema can result from opening of tight junctions at the BBB or an increase in pinocytotic activity. Damage to the BBB from ischemia/stroke can result in poor clinical outcomes during stroke recovery, such as vasogenic brain edema and inflammation. In addition, changes in BB transport characteristics may influence the transport of clinically useful medications used to either treat the ischemic episode or medicate other disease stages. Our major hypothesis is that hypoxia/aglycemia and reperfusion (associated with stroke) alters both the expression of BB specific proteins and the permeability and transport of critical solutes across the BBB, thereby contributing to the development and severity of stroke. To investigate this hypothesis, our major objective and specific aims are to investigate and quantify the effect of hypoxia/aglycemia/reoxygenation on the endothelial cells of the BBB by quantifying effects on cell resistance, permeability, tight junctional protein/cytoskeletal protein expression and transcriptional/post-transcriptional expression of specific proteins associated with hypoxia. We will also identify the role in calcium in hypoxia/aglycemia/reoxygenation and determine the role of astrocytes. The techniques we will use are both in vitro and in situ coupling our experience of analytical biochemistry and vascular biology in a focused program to study the effect of hypoxic/aglycemic stress on endothelial cells of the BBB.
StatusFinished
Effective start/end date1/1/0012/31/10

Funding

  • National Institutes of Health: $50,000.00
  • National Institutes of Health: $274,841.00
  • National Institutes of Health: $339,490.00
  • National Institutes of Health: $347,086.00
  • National Institutes of Health: $236,210.00
  • National Institutes of Health: $291,580.00
  • National Institutes of Health: $330,188.00
  • National Institutes of Health: $330,188.00
  • National Institutes of Health: $330,188.00
  • National Institutes of Health: $283,085.00
  • National Institutes of Health: $242,968.00

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Endothelial Cells
Stroke
Blood-Brain Barrier
Brain Edema
Permeability
Reperfusion
Cytoskeletal Proteins
Transcription Factors
Ischemia
Hypoxia
Tight Junction Proteins
Tight Junctions
Protein Transport
Encephalitis
Microvessels
Astrocytes
Biochemistry
Brain Injuries
Protein Kinase C
Blood Vessels

ASJC

  • Medicine(all)
  • Neuroscience(all)