The Bradykinin B2 Receptor Agonist (NG291) Causes Rapid Onset of Transient Blood-Brain Barrier Disruption Without Evidence of Early Brain Injury.

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I am writing a thesis on my work on the utilization of a bradykinin B2 receptor agonists that we have found capable of transiently increasing blood brain barrier permeability without the risks associated with kinin mediated BBB permeability (induction of vasogenic edema, astrocyte activation, nerodegeneration, and neuroinflammation). I would like help with the introduction to this work.

It should contain:

Introduction to the Blood-brain barrier physiology and function
Introduction to the neurovascular unit and the functions of:
- Endothelial cells
- Astrocytes
- pericytes
Paracellular (tight junctions) and transcellular transport mechanisms (endocytosis, albumin transport, caveolae, PgP efflux transporters)
An introduction to the kallikrein kinin system
- Bradykinin and kallidin formation
- Bradykinin and kallidin receptor specificity to bradykinin B2 receptor
- Bradykinin and kallidin metabolized by carboxypeptidases N/M into peptide sequences with high affinity to bradykinin B1 receptors
- Bradykinin B2 vs B1 receptor signaling in brain endothelial cells
  - Note: we are lookeing to selectively activate Bradykinin B2 receptor activity without the Bradykinin B1 receptor recruitment of an exaggerated immune response. B2 receptor is internalized with excessive stimulation leading to a self limited effect. continued B1 receptor signaling leads to exponential activity that can lead to cell death and an exaggerated immune response that could exacerbate a patient’s condition.
The potential of physiologically stable selective bradykinin B2 receptor agonists in:
- transiently increasing blood brain barrier permeability to facilitate drug delivery to the brain (emphasize on this)
- Facilitating glucose delivery via eNOS mediated increase in GLUT expression in patients with Alzheimers disease
- Alzheimers disease by increasing PgP efflux transporter activity leading to increased efflux of beta amyloid.

I will be uploading a paper that has been submitted for publication for reference.

I am using Mendeley for citations in the thesis.

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