LACK OF PURKINJE-CELL LOSS IN ADULT-RAT CEREBELLUM FOLLOWING PROTRACTED AXOTOMY - DEGENERATIVE CHANGES AND REGENERATIVE ATTEMPTS OF THE SEVERED AXONS

The cerebellar Purkinje cells, due to their geometrical disposition an d their high calbindin content, offer an optimal system in which to te st the adequacy of current opinions an axotomy effects. We have, there fore, 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 morphologi cal changes in their dendrites, cell bodies, and axons. We have also s earched for simultaneous changes in glial cells and vascularization by using cell type-specific markers. In addition, an ultrastructural stu dy of Purkinje cells, 7 days after large electrolytic lesions affectin g the white matter and the overlying granular layer, was carried out t o determine whether amputation of the recurrent collateral system prov okes a fast neuronal death. Neither the Purkinje cells axotomized clos e to their cell bodies (electrolytic lesions) nor those axotomized in the white matter (cerebellar transection) degenerated. Thus, this stud y demonstrates that Purkinje cells are extremely resistant to axotomy; those severed in the white matter at distances varying from 100 mu m to 3 mm remain alive for as long as 6 months. At all survival times st udied, 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 lesio n, although they later differed in their time course and spatial distr ibution. It is remarkable that the distal segments of the central stum ps of the cut axons survived in large numbers without any apparent ret raction, with their terminal varicosities apposed to the wall of the w ound cavity even 6 months after the lesion. Nevertheless, these segmen ts were thinner than normal Purkinje cell axons (axonal atrophy). Desp ite this apparent immutability, some regenerative attempts did occur i n the severed axons, such as axonal sprouts penetrating the deeper reg ion of the granular layer in zones close to the lesion, presence of ar ciform axons, and hypertrophy of the recurrent collateral system. Howe ver, the Purkinje cell axons did not regenerate, and these neurons rem ained separated from their targets by a cavity in virtually all cases. (C) 1994 Wiley-Liss, Inc.