Post-natal changes in myelination involved in rodent pain processing pathways
Lead Research Organisation:
University of Nottingham
Department Name: School of Life Sciences
Abstract
The Brown/Hathway laboratories are dedicated to the principles of the 3Rs, which are incorporated into our laboratory practices. This project will use a 3Rs approach to the experimental procedures, using both sciatic nerves from each animal to significantly reduce the number of rats used in the study and multielectrode arrays to increase the yield of data from each animal.
Peripheral nerves are at risk from a variety of pathological conditions including type 2 diabetes, trauma, ischaemia, peripheral neuropathies and systemic hypoglycaemia. The most important functional consequence of such pathology is impaired nerve conduction, which can be measured using electrophysiological techniques, with post insult recovery of conduction an indicator of the degree of injury incurred by the nerve. Peripheral nerves can be mixed motor and sensory comprising both myelinated (A) and unmyelinated (C) fibres, with each fibre sub-type selectively susceptible to particular pathologies.
The suction electrode model was initially developed in the rodent optic nerve in the late 1980s, since when it has successfully been used to study the mechanisms of anoxic and/or aglycemia injury to central white matter. Equivalent information in peripheral nerves is lacking. We have demonstrated a new approach to studying peripheral nerve conduction (http://dx.doi.org/10.1113/JP275680), which allows simultaneous recording of the A and C fibres. Since these recordings emanate from the same nerve under identical experimental conditions meaningful comparisons can be made between fibre sub-types. This in vitro model can be used to record nerve conduction for over 8 hours, thus the ratio of post/pre insult conduction can provide a model with which to assess the benefits of clinically relevant neuroprotective strategies in models of both crush and metabolic injury to peripheral nerves.
The aims of the project are:
a. Establish the response of the nerves to exposure to aglycaemic conditions and determine the ability of metabolically relevant substrates in supporting condition
b. Establish any differences in the role of Schwann cells in passing lactate to the axons be it A or C fibres.
RICH L R & BROWN A M. Fibre sub-type specific conduction reveals metabolic function in mouse sciatic nerve. Journal of Physiology 596.10 (2018) p.1795-1812
Peripheral nerves are at risk from a variety of pathological conditions including type 2 diabetes, trauma, ischaemia, peripheral neuropathies and systemic hypoglycaemia. The most important functional consequence of such pathology is impaired nerve conduction, which can be measured using electrophysiological techniques, with post insult recovery of conduction an indicator of the degree of injury incurred by the nerve. Peripheral nerves can be mixed motor and sensory comprising both myelinated (A) and unmyelinated (C) fibres, with each fibre sub-type selectively susceptible to particular pathologies.
The suction electrode model was initially developed in the rodent optic nerve in the late 1980s, since when it has successfully been used to study the mechanisms of anoxic and/or aglycemia injury to central white matter. Equivalent information in peripheral nerves is lacking. We have demonstrated a new approach to studying peripheral nerve conduction (http://dx.doi.org/10.1113/JP275680), which allows simultaneous recording of the A and C fibres. Since these recordings emanate from the same nerve under identical experimental conditions meaningful comparisons can be made between fibre sub-types. This in vitro model can be used to record nerve conduction for over 8 hours, thus the ratio of post/pre insult conduction can provide a model with which to assess the benefits of clinically relevant neuroprotective strategies in models of both crush and metabolic injury to peripheral nerves.
The aims of the project are:
a. Establish the response of the nerves to exposure to aglycaemic conditions and determine the ability of metabolically relevant substrates in supporting condition
b. Establish any differences in the role of Schwann cells in passing lactate to the axons be it A or C fibres.
RICH L R & BROWN A M. Fibre sub-type specific conduction reveals metabolic function in mouse sciatic nerve. Journal of Physiology 596.10 (2018) p.1795-1812
Organisations
People |
ORCID iD |
| Angus Brown (Primary Supervisor) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/T008369/1 | 01/10/2020 | 30/09/2028 | |||
| 2746261 | Studentship | BB/T008369/1 | 01/10/2022 | 30/09/2026 |