Lack of Purkinje cell loss in adult rat cerebellum following protracted axotomy: degenerative changes and regenerative attempts of the severed axons

J Comp Neurol. 1994 Sep 8;347(2):211-32. doi: 10.1002/cne.903470206.

Abstract

The cerebellar Purkinje cells, due to their geometrical disposition and their high calbindin content, offer an optimal system in which to test the adequacy of current opinions on axotomy effects. We have, therefore, analyzed with calbindin immunostaining the morphological changes of Purkinje cells from 1 day to 6 months after axonal section in the cerebellar white matter. This method allows us to study the morphological changes in their dendrites, cell bodies, and axons. We have also searched for simultaneous changes in glial cells and vascularization by using cell type-specific markers. In addition, an ultrastructural study of Purkinje cells, 7 days after large electrolytic lesions affecting the white matter and the overlying granular layer, was carried out to determine whether amputation of the recurrent collateral system provokes a fast neuronal death. Neither the Purkinje cells axotomized close to their cell bodies (electrolytic lesions) nor those axotomized in the white matter (cerebellar transection) degenerated. Thus, this study demonstrates that Purkinje cells are extremely resistant to axotomy; those severed in the white matter at distances varying from 100 microns to 3 mm remain alive for as long as 6 months. At all survival times studied, axotomized Purkinje cells exhibited few changes in their somata and dendrites, as well as in their glial microenvironment. The major changes occurred in the axonal compartment. Axonal alterations, namely the presence of torpedoes and hypertrophy of the recurrent collateral system, were early events already noticeable 24 hours after the lesion, although they later differed in their time course and spatial distribution. It is remarkable that the distal segments of the central stumps of the cut axons survived in large numbers without any apparent retraction, with their terminal varicosities apposed to the wall of the wound cavity even 6 months after the lesion. Nevertheless, these segments were thinner than normal Purkinje cell axons (axonal atrophy). Despite this apparent immutability, some regenerative attempts did occur in the severed axons, such as axonal sprouts penetrating the deeper region of the granular layer in zones close to the lesion, presence of arciform axons, and hypertrophy of the recurrent collateral system. However, the Purkinje cell axons did not regenerate, and these neurons remained separated from their targets by a cavity in virtually all cases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology*
  • Cell Death
  • Female
  • Necrosis
  • Nerve Degeneration / physiology*
  • Nerve Regeneration / physiology*
  • Purkinje Cells / ultrastructure*
  • Rats
  • Rats, Wistar / anatomy & histology*
  • Time Factors