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Published on: January 14, 2014
Growth of brain tissue grafts is dependent upon host age
M Eriksdotter-Nilsson1, L Olson
1Department of Histology and Neurobiology, Karolinska Institute, Stockholm, Sweden.
Insights
Host age significantly impacts brain graft growth and vascularization, with older rats showing reduced development. However, older hosts can still support trophic stimulation in secondary grafts, offering hope for neurodegenerative disease treatments.
Area of Science:
- Neuroscience
- Developmental Biology
- Transplantation Biology
Background:
- Host age is a critical factor influencing the success of neural grafts.
- Understanding age-related changes in the host environment is crucial for optimizing transplantation strategies.
Purpose of the Study:
- To investigate the effect of host age on the growth, vascularization, and glial response of intraocular brain grafts.
- To assess the capacity for trophic stimulation in grafts within aged hosts.
Main Methods:
- Intraocular grafting of cortex cerebri, hippocampus, septum, cerebellum, and locus coeruleus into young (1.5- and 3-month-old) and aged (16-17-month-old) rats.
- Immunofluorescence staining for laminin (vascularization) and glial fibrillary acidic protein (gliosis).
- Analysis of neurofilament immunoreactivity and assessment of secondary graft growth.
Main Results:
- Grafts in older hosts exhibited significantly reduced growth, abnormal vascularization, and increased gliosis compared to younger hosts.
- Locus coeruleus grafts showed less pronounced age-related growth differences.
- Secondary cortex grafts demonstrated trophic stimulation capacity in aged hosts, with improved vascularization and reduced gliosis compared to single grafts.
Conclusions:
- Host age significantly influences the growth and morphology of various brain grafts.
- Aged hosts retain the capacity for trophic stimulation of neural grafts, particularly evident in secondary cortex grafts.
- These findings have implications for using brain transplantation to treat age-related neurodegenerative diseases.
Abstract:
Growth of grafts of cortex cerebri, hippocampus, septum and cerebellum in oculo were significantly reduced in 16--17-month-old hosts as compared to growth in 3-month-old and 1.5-month-old rat hosts. (Host age is given as the age of the recipients at the time of grafting.) This growth difference was less pronounced in locus coeruleus grafts. The vascular network (as observed with laminin immunofluorescence) in cortex cerebri, hippocampus, cerebellum and septum grafts in 16--17-month-old hosts was abnormal with few thick-walled vessels in clusters as compared to the more 'normal' vascularization found in 1.5-month-old hosts with a high number of thin-walled blood vessels evenly distributed throughout the grafts. Grafts in the oldests hosts were markedly more gliotic than grafts in 1.5- and 3-month-old hosts as evaluated using immunofluorescence with antibodies against glial fibrillary acidic protein. Neurofilament immunoreactivity in the grafts seemed not to be influenced by host age. When a second cortex cerebri or hippocampus graft was placed into contact with a previously grafted locus coeruleus graft, the second graft grew less well in 16--17-month-old hosts as compared to 1.5-month-old hosts. When cortex cerebri was added to a previously grafted cortex cerebri graft, the second graft in both 16--17- and 3-month-old hosts grew to larger sizes than the corresponding single cortex grafts, although the growth differences between the two groups of hosts described above were still maintained. Thus, cortex grafts in 16--17-month-old hosts still have the ability to become trophically stimulated. The vascularization of the second graft in both groups was almost normalized and the gliotic reaction was less pronounced in the second grafts in both groups as compared to the single cortex grafts. In conclusion, the present results indicate that host age affects growth and morphology of intraocular single grafts from several brain regions. Using double grafts of cortex cerebri it was shown that grafts in 16-17-month-old hosts still had the capacity to become trophically stimulated. Data on brain transplants in older hosts are important in view of clinical possibilities to use transplantation strategies to counteract the symptoms of neurodegenerative diseases, which usually occur in old patients.
