Adrenal Medullary Autografts in Anterior Eye Chamber, Lateral Ventricle and Striatum of Adult Rats: A Long Term Study
JOURNAL OF NEURAL TRANSPLANTATION & PLASTICITY
Adrenal Medullary Autografts in Anterior Eye Chamber, Lateral Ventricle and Striatum of Adult Rats: A Long Term Study
Ashok Kumar Shetty 0 1
Gomathy Gopinath 0 1
P.N. Tandon 0 1
0 Reprint address: Professor Gomathy Gopinath Department
1 National Neural Transplant Unit, All India Institute
SUMMARY The neurobiological basis for the short-term recovery in Parkinson's patients and experimental animals grafted with adrenal medulla is not yet clear. Structural details of the grafted chromaffin cells are also not available. In the present study, autografts of adrenal medulla in the anterior eye chamber, lateral ventricle and striatum of adult rats were studied for 360 days. Though a large number of cells degenerated, a few healthy chromaffin cells survived up to 360 days in the anterior eye chamber. In the ventricular and striatal regions, cells degenerated more rapidly, and a few surviving cells were seen only up to 120 and 150 days, respectively. Degeneration of the cells was evident from the alteration of the cytoplasmic granules, appearance of vacuoles and lysosomes, rapid decline in the number of TH and DBH positive cells and diffusion of enzymes in the intercellular region. Only lymphocytes and connective tissue cells were seen in the ventricle after 120 days, while outlines of a few chromaffin cells and background fluorescence were still evident in the striatum up to 150 days. In some of the intrastriatal transplants, morphologically identifiable Schwann cells were present and, in one transplant, there was evidence of myelination of axons by Schwann cells. These axons were obviously derived from the adjacent host tissue. From the findings it has been concluded that autografts of adrenal medulla survive for only a Hmited period of time on transplantation to the central nervous system and anterior eye chamber. Survival seemed to be better in the anterior eye chamber than at the sites preferentially chosen for treating Parkinson's patients or experimental animals.
Adrenal medulla graft; Parkinson's disease; transplantation; anterior eye chamber; striatum; transplant morphology
INTRODUCTION
The chromaffin cells of adrenal medulla, known
for producing dopamine as an intermediary in
the synthetic pathway of epinephrine/19/, are
used for grafting in rats and monkeys to reverse
the deficits induced by cheInieal denervation of
the striatum/3,9,10,12,20,25,26/. Results of these
experiments prompted the use of adrenal
medulla autografts in the treatment of
Parkinson’s patients/2,16-18/. Only moderate recovery
of short duration is reported so far in a small
proportion of patients/15,16/. The
neurobiological basis of such recovery is still unexplained.
Survival of allografts of ehromaffin cells in the
striatum of rats denervated chemically and
amelioration of some of the deficits are reported in
some studies by using fluorescence
histoehemistry and immunolabelling/8,12/. Continued
survival of grafted chromaffin cells was
demonstrated by Stromberg et al. /25,26/ only by the
infusing of NGF into the implant site. Hansen et
al. /14/ reported complete degeneration of the
autografted adrenal medullary cells by one
month in Cebus monkeys treated with MPTP. A
recent autopsy report also shows complete
degeneration of the adrenal medullary autograft in
a Parkinson’s patient/23L These reports have
brought to light the necessity for a more detailed
basic study than hitherto exists, on the
transplanted adrenal medullary cells. Transplanted
adrenal chromaffin cells grafted to the anterior
chamber of the eye were shown to have achieved
neuronal characteristics with their processes
innervating co-grafted cerebral cortex /21,22/.
Similar observations were also recorded in
culture of chromaffin cells in the absence of
corticosteroids /27-29/. The present study was
undertaken to analyse the morphological details of
the autografts of adrenal medulla in the anterior
eye chamber, lateral ventricle and striatum.
MATERIALS AND METHODS
Adult Wistar rats of stock bred colony
weighing 150 to 200 g were used in this study.
The left adrenal gland, after removal from an
anaesthetised (ketamine, 10mg/kg body weight)
rat, was dissected to free the medulla from the
cortex in sterile lactated Ringer’s solution under
an operation microscope. Standard techniques
were used to transplant the medullary grafts into
the anterior eye chamber, lateral ventricle and
striatum /4,5,11,21/. Behaviour and
vascularisation of the intraoeular grafts were observed
under an operation microscope. On 30, 60, 90,
120, 150, 180, 300 and 360 post-transplantation
days, the rats were sacrificed and the transplants
were processed for morphological and
histochemical analysis. The number of transplants
studed on each experimental day is listed in
Table 1.
Tissue preparation for light and
microscopy
electron
After anaesthetising the animals, the
intraocular grafts were rapidly dissected free
from the host iris and were fixed (...truncated)