Astrogliosis has Different Dynamics after Cell Transplantation and Mechanical Impact in the Rodent Model of Parkinson's Disease.

Abstract

Background:Transplantation of fetal mesencephalic tissue is a well-established concept for functional reinnervation of the dopamine-depleted rat striatum. However, there is no extensive description of the glial response of the host brain following this procedure.Aims:The present study aimed to quantitatively and qualitatively analyse astrogliosis surrounding intrastriatal grafts and compare it to the reaction to mechanical injury with the transplantation instrument only.Study Design:Animal experimentation.Methods:The standard 6-hydroxydopamine-induced unilateral model of Parkinson’s disease was used. The experimental animals received transplantation of a single-cell suspension of E14 ventral mesencephalic tissue. Control animals (sham-transplanted) were subjected to injury by the transplantation cannula, without injection of a cell suspension. Histological analyses were carried out 7 and 28 days following the procedure by immunohistochemistry assays for tyrosine hydroxylase and glial fibrillary acidic protein. To evaluate astrogliosis, the cell density and immunopositive area were measured in distinct zones within and surrounding the grafts or the cannula tract.Results:Statistical analysis revealed that astrogliosis in the grafted striatum increased from day 7 to day 28, as shown by a significant change in both cell density and the immunopositive area. The cell density increased from 816.7±370.6 to 1403±272.1 cells/mm2 (p<0.0001) аnd from 523±245.9 to 1164±304.8 cells/mm2 (p<0.0001) in the two zones in the graft core, and from 1151±218.6 to 1485±210.6 cells/mm2 (p<0.05) for the zone in the striatum immediately adjacent to the graft. The glial fibrillary acidic protein-expressing area increased from 0.3109±0.1843 to 0.7949±0.1910 (p<0.0001) and from 0.1449±0.1240 to 0.702±0.2558 (p<0.0001) for the same zones in the graft core, and from 0.5277±0.1502 to 0.6969±0.1223 (p<0.0001) for the same area adjacent to the graft zone. However, astrogliosis caused by mechanical impact only (control) did not display such dynamics. This finding suggests an influence of the grafted cells on the host’s glia, possibly through cross-talk between astrocytes and transplanted neurons.Conclusion:This bidirectional relationship is affected by multiple factors beyond the mechanical trauma. Elucidation of these factors might help achieve better functional outcomes after intracerebral transplantation.