The Nervous System

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The Nervous System

• The human nervous system can be divided into two
  parts the central nervous system (CNS) and the
  peripheral nervous system (PNS)
• http//pennhealth.com/health_info/animationplayer/
  nerve_conduction.html

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Central Nervous System

• Drugs that affect the CNS can
• Selectively relieve pain
• Reduce fever
• Suppress disordered movement
• Induce sleep or arousal
• Reduce appetite
• Allay the tendency to vomit
• Be used to treat anxiety, depression,
  schizophrenia, Parkinsons Disease, Alzheimers
  Disease, epilepsy, migraine, etc.

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How do drugs work in the CNS?

• A central underlying concept of
  neuropharmacology is that drugs that influence
  behavior and improve the functional status of
  patients with neurological or psychiatric
  diseases act by enhancing or blunting the
  effectiveness of specific combinations of
  synaptic transmitter actions.

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Blood Brain Barrier (BBB)

• A physiological mechanism that alters the
  permeability of brain capillaries, so that some
  substances, such as certain drugs, are prevented
  from entering brain tissue, while other
  substances are allowed to enter freely.
• The separation of the brain, which is bathed in a
  clear cerebrospinal fluid, from the bloodstream.
  The cells near the capillary beds external to the
  brain selectively filter the molecules that are
  allowed to enter the brain, creating a more
  stable, nearly pathogen-free environment.

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Diagram of a cerebral capillary enclosed in
astrocyte end-feet. Characteristics of the
blood-brain barrier are indicated (1) tight
junctions that seal the pathway between the
capillary (endothelial) cells (2) the lipid
nature of the cell membranes of the capillary
wall which makes it a barrier towater-soluble
molecules (3), (4), and (5) represent some of
the carriers and ion channels (6) the 'enzymatic
barrier'that removes molecules from the blood
(7) the efflux pumps which extrude fat-soluble
molecules that have crossed into the cells
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Blood-Brain-Barrier

• Oxygen, glucose, and white blood cells are
  molecules that are able to pass through this
  barrier. Red blood cells cannot.

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Blood Brain Barrier

• The blood-brain barrier (abbreviated BBB) is
  composed of endothelial cells packed tightly in
  brain capillaries that more greatly restrict
  passage of substances from the bloodstream than
  do endothelial cells in capillaries elsewhere in
  the body.
• Processes from astrocytes surround the epithelial
  cells of the BBB providing biochemical support to
  the epithelial cells.
• The BBB should not be confused with the
  blood-cerebrospinal fluid barrier (BCB), a
  function of the choroid plexus.

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History of the BBB

• The existence of such a barrier was first noticed
  in experiments by Paul Ehrlich in the late-19th
  century. Ehrlich was a bacteriologist who was
  studying staining, used for many studies to make
  fine structures visible. Some of these dyes,
  notably the aniline dyes that were then popular,
  would stain all of the organs of an animal except
  the brain when injected. At the time, Ehrlich
  attributed this to the brain simply not picking
  up as much of the dye.

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• However, in a later experiment in 1913, Edwin
  Goldmann (one of Ehrlich's students) injected the
  dye into the spinal fluid of the brain directly.
• He found that in this case the brain would become
  dyed, but the rest of the body remained dye-free.
  This clearly demonstrated the existence of some
  sort of barrier between the two sections of the
  body.

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History of the BBB

• At the time, it was thought that the blood
  vessels themselves were responsible for the
  barrier, as there was no obvious membrane that
  could be found.
• It was not until the introduction of the scanning
  electron microscope to the medical research
  fields in the 1960s that this could be
  demonstrated. The concept of the blood-brain
  (then termed hematoencephalic) barrier was
  proposed by Lina Stern in 1921.

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What is the purpose of the BBB?

• The blood-brain barrier protects the brain from
  the many chemicals flowing around the body.
• For example, many bodily functions are controlled
  by hormones, which are detected by receptors on
  the plasma membranes of targeted cells throughout
  the body.
• The secretion of many hormones are controlled by
  the brain, but these hormones generally do not
  penetrate the brain from the blood, so in order
  to control the rate of hormone secretion
  effectively, there are specialized sites where
  neurons can "sample" the composition of the
  circulating blood.

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• At these sites, the blood-brain barrier is
  'leaky' these sites include three important
  'circumventricular organs', the subfornical
  organ, the area postrema and the organum
  vasculosum of the lamina terminalis (OVLT).
• The blood-brain barrier is also an effective way
  to protect the brain from common infections. Thus
  infections of the brain are very rare however,
  as antibodies are too large to cross the
  blood-brain barrier, when infections of the brain
  do occur they can be very serious and difficult
  to treat.

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How does the BBB affect the design of therapeutic
agents?

• Mechanisms for drug targeting in the brain
  involve going either "through" or "behind" the
  BBB.
• Modalities for drug delivery through the BBB
  entail disruption of the BBB by osmotic means,
  biochemically by the use of vasoactive substances
  such as bradykinin, or even by localized exposure
  to high intensity focused ultrasound (HIFU).
• The potential for using BBB opening to target
  specific agents to brain tumors has just begun to
  be explored.

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The Blood Brain Barrier

• http//www.clinicaloptions.com/HIV/Management20Se
  ries/NeuroAIDS/Animation/Blood20Brain20Barrier.a
  spx