Project Summary
The proposed research uses a combination of molecular neuroscience and immunology techniques to
investigate the relationship between the nervous system and immune system after injury. The nervous system
is divided into the central nervous system (CNS), which includes the brain and the spinal cord, and the
peripheral nervous system (PNS). Neurons are the main cells of the nervous system and are composed of 3
parts: a cell body, dendrites that are used for short-distance communication, and a single axon which is used
for long distance communication. The PNS has the ability to regenerate following axonal injury, while this fails
to occur in after injury to the CNS. The result of this is usually long-term functional deficits following injuries to
the brain and spinal cord. Work within the neuroimmunology field has highlighted a dichotomy in inflammatory
pathways that are activated and/or sustained following injury to the CNS and the PNS. This work suggests that
inflammation promotes regeneration in the PNS, while it is one of the inhibitory factors to regeneration in the
CNS.
The long-term objective of this proposed research is to understand the relationship between
inflammation and axon regeneration within the PNS. Using rodent models of sciatic nerve injury, the immune
response both spatially and temporally will be characterized. Importantly, use of transgenic mouse models will
elucidate the roles that both tissue resident immune cells and blood-borne myeloid cells have during this
inflammatory cascade. Further, while the sciatic nerve injury model is well known for being regeneration
competent, this competency will be altered by utilizing the Sarm1-/- mouse line that shows a failure in Wallerian
degeneration. Wallerian degeneration is an important cascade following injury that occurs very efficiently in the
PNS (but not in the CNS), and helps remove debris so the axons can regenerate. This work will ask whether
Wallerian degeneration is the trigger for the inflammatory cascade and if this is essential for axons to
regenerate.
Research students will utilize cutting edge molecular biology techniques to ask these questions. Their
findings will contribute to understanding of inflammatory mediated neural repair and help fill in several gaps in
knowledge that could improve the ability to develop therapeutic strategies for CNS injuries. Students will be
directly supervised by Dr. Kalinski and will participate in experimental design, data collection, interpretation,
and dissemination of results. Furthermore, portions of the experiments proposed will be incorporated into the
laboratory components of a course taught by Dr. Kalinski that will reach an additional 32 students a year.
Undergraduate and master’s students in the Kalinski laboratory and in her class will be positioned to make
discoveries that have a direct impact on the understanding of immune mediated neural repair. These
experiences will serve them well as they pursue careers and further education after graduation.