The Institute investigates development and regeneration in several animal models, such as newts, lampreys, frogs, and fish. Understanding the regenerative processes in these systems provide important information about mammalian systems and their relative lack of regeneration of their nervous system.
Reduction of the Current of Injury Leaving the Amputation Inhibits Limb
Regeneration in the Red Spotted Newt
Lisa S. Jenkins,
Bradley S. Duerstock and
Richard B. Borgens,
Center for Paralysis Research,
Department of Basic Medical Sciences,
School of Veterinary Medicine,
Purdue University
Immediately following amputation of the limb in salamanders, a strong, steady, and
polarized flow of ionic current is produced by the injury. Current flows in a
proximodistal direction within the limb stump and is associated with a fall in
electrical potential of about 50 mV/mm near the stump's end. 
This current is
electrogenically driven by the Na+ dependent, internally positive transcutaneous
voltage of the intact skin of the limb stump. Reduction of this EMF, the skin's
battery, by topical application of Na+ blocking agents leads to inhibition or
disruption of normal limb regeneration. This suggests electrical factors are a
critical control of limb regeneration. Here we test another means to reduce the
injury current and its associated electrical field within the forelimb stump of red
spotted newts. A fine (40 gauge), insulated, multi-strand wire was inserted beneath
the skin of the animal's back, with the uninsulated portion terminating either at
the shoulder region or at the base of the tail. When this cathodal (negative)
electrode is connected to a regulated current source, sufficient current was pulled
into the stump end from an external anode (placed in the water the animal was
immersed in) to markedly reduce or null the endogenous current for the first eight
days following amputation. The extent of limb regeneration in sham treated and
experimentally treated animals was determined 1 month following amputation at the
elbow. Sham treated animals regenerated normally, most all producing digits within
this time. Limb regeneration was completely arrested, or caused to be strikingly
hypomorphic, in half of the experimentally treated animals. This effect was
independent of where the subcutaneous electrode was placed and suggests that
electrical (physiological) factors are indeed a critical control of limb
regeneration in Urodeles. Dev. Biol. 178, 251-262 (1996)
To the left shows a normal regenerated newt forelimb. 3D visualization allows one
to view the skeletal elements within the limb a varying depths of the tissue. The
limb was amputated above the elbow and fully regenerated after one month's time.
Approximately 90 sections stained with Mallory's trichrome was used to construct
this 3D image. Active regeneration of a similarly amputated
limb can be seen in the video above.