Injury-Induced HSP27 Expression in Peripheral Nervous Tissue Is Not Associated with Any Alteration in Axonal Outgrowth after Immediate or Delayed Nerve Repair

Abstract

We investigated injury-induced heat shock protein 27 (HSP27) expression and its association to axonal outgrowth after injury and different nerve repair models in healthy Wistar and diabetic Goto-Kakizaki rats. By immunohistochemistry, expression of HSP27 in sciatic nerves and DRG and axonal outgrowth (neurofilaments) in sciatic nerves were analyzed after no, immediate, and delayed (7-day delay) nerve repairs (7- or 14-day follow-up). An increased HSP27 expression in nerves and in DRG at the uninjured side was associated with diabetes. HSP27 expression in nerves and in DRG increased substantially after the nerve injuries, being higher at the site where axons and Schwann cells interacted. Regression analysis indicated a positive influence of immediate nerve repair compared to an unrepaired injury, but a shortly delayed nerve repair had no impact on axonal outgrowth. Diabetes was associated with a decreased axonal outgrowth. The increased expression of HSP27 in sciatic nerve and DRG did not influence axonal outgrowth. Injured sciatic nerves should appropriately be repaired in healthy and diabetic rats, but a short delay does not influence axonal outgrowth. HSP27 expression in sciatic nerve or DRG, despite an increase after nerve injury with or without a repair, is not associated with any alteration in axonal outgrowth.

Exposure to hand-held vibrating tools and biomarkers of nerve injury in plasma: a population-based, observational study

“…The caspases indicate apoptosis of, for example, Schwann cells that occur in a peripheral nerve after injury in experimental systems 32. A more severe experimental nerve injury may also induce increased upregulation of HSP27 locally in the peripheral nerve as well as in sensory neurons 33. Furthermore, a generalised neuropathy, such as diabetic neuropathy, increases plasma levels of HSP27, with an association between plasma levels and protection of nerve function 17 18.…”

“… 32 A more severe experimental nerve injury may also induce increased upregulation of HSP27 locally in the peripheral nerve as well as in sensory neurons. 33 Furthermore, a generalised neuropathy, such as diabetic neuropathy, increases plasma levels of HSP27, with an association between plasma levels and protection of nerve function. 17 18 Other neuropathies, including diabetic neuropathy, also increase a variety of plasma proteins that indicate affection and injury to the nerve fibres, that is, axons and Schwann cells, as well as to vascular components.…”

Quantification of heat shock proteins in the posterior interosseous nerve among subjects with type 1 and type 2 diabetes compared to healthy controls

“…Such signs of regeneration are seen as regenerative clusters among such subjects at specific topographical locations in the nerve depending on the degeneration process (Dahlin et al, 2020 ). De- and re-generation after nerve injury and repair in healthy rats and in rats with diabetes (i.e., Goto-Kakizaki rats, resembling T2D) induce the upregulation of HSP27 both locally in the injured nerve as well as in the sensory neurons in the dorsal root ganglion (Stenberg et al, 2021 ). However, such increased local expression of HSP27 is not related to the outgrowth of nerve fibers, i.e., regeneration, after the nerve repair (Stenberg et al, 2021 ).…”

“…De- and re-generation after nerve injury and repair in healthy rats and in rats with diabetes (i.e., Goto-Kakizaki rats, resembling T2D) induce the upregulation of HSP27 both locally in the injured nerve as well as in the sensory neurons in the dorsal root ganglion (Stenberg et al, 2021 ). However, such increased local expression of HSP27 is not related to the outgrowth of nerve fibers, i.e., regeneration, after the nerve repair (Stenberg et al, 2021 ). Higher plasma levels of HSP27 have been found in T2D subjects with better nerve function and fewer signs of neuropathy (Pourhamidi et al, 2011 ) and are lower in T1D subjects with large nerve fiber dysfunction (Pourhamidi et al, 2014 ), indicating that HSP27, and potentially some other HSPs, is neuroprotective.…”

The Dynamics of Nerve Degeneration and Regeneration in a Healthy Milieu and in Diabetes

“…The detailed mechanisms related to Schwann cell behavior after nerve injury and regeneration in diabetes are still not fully clarified, although differences have been observed concerning the expression of transcription factors and apoptotic factors [30,118,119] as well as how they interact with other key players [10]. However, Schwann cells in adipose tissue, including adipose-derived stem cells [120], may regulate the plasticity of the nerves in such a tissue [121].…”