In recent years, the grafting of tissues into
the central nervous system (CNS) has evolved from an
intriguing technique whereby development, function and
plasticity of the nervous system may be studied, to a
powerful new tool for the replacement of cells lost in
degenerative neurological disorders such as Parkinson's
and Alzheimer's disease. Remarkable effects of fetal
grafts in animal models have promoted the application
of this new technology in the clinical setting. In the
past few years, clinical trials of fetal transplants
into Parkinsonian patients have been started with promising
results.
Research at the Neural Transplantation Laboratory is focused in two main
areas. The first one deals with the elucidation of the mechanism or mechanisms
by which neural grafts produce functional recovery in animal models for
Parkinson's disease. We are particularly interested in the restoration
of the damaged synaptic circuitry in the lesioned animal by the transplanted
cells, and the regulation of graft function by the host. The second area
of research addresses the shortcoming of current techniques for intracerebral
grafting that include low graft survival, suboptimal graft integration,
and implantation trauma. Considerable effort is placed in improving the
techniques for cell suspension preparation, storage, and implantation.
The use of neurotrophic factors in improvement of graft survival is currently
an important area of research in our group.
Recently the laboratory has expanded the research interest to include
the development of transplantation strategies to restore neuronal function
in the spinalized animal model for the treatment of spinal cord injury
and cable grafting techniques to restore function in a model of optic
nerve damage for the treatment of eye injury.
Immunocytochemical techniques both at the light and electron microscope
levels, in situ hybridization methods for assessing the mRNA levels of
different neurotransmitters in the host and graft are routinely used
in the laboratory. A great deal of microsurgical and stereotactic procedures
are used for lesioning and grafting into the adult CNS. We have recently
incorporated a tissue culture facility and in the near future neuronal
culture and genetic engineering will be routinely carried out in the
laboratory.
The laboratory is an essential part of the Halifax Neural Transplantation
Program, the only program of its kind in Canada . We provide the basic
research component of the clinical program at the Victoria General Hospital
site of the QEII Health Sciences Centre.
Research Support:
QEII Health Sciences Centre
Department of Surgery, Victoria General Hospital
Publications:
Mendez, I. , Elisevich , K., Naus , C., and Flumerfelt , B. Restoration
of nigro-striatalsynaptic circuitry, striatal mRNA expression and motor
symmetry following embryonic substantia nigra grafts. Clinical Neurosurgery
(1991) Vol. 38, Chapter 10, 180-209
Mendez, I. , Elisevich , K. and Flumerfelt , B. Dopaminergic innervation
of substance P-containing striatal neurons by fetal nigral grafts: an
ultrastructural double labelling immunocytochemical study. The Journal
of Comparative Neurology (1991) 308: 66-78
Mendez, I. , Elisevich , K. and Flumerfelt , B. Substance P synaptic
interactions with dopaminergic and GABAergic neurons in the rat substantia
nigra : an ultrastructural double labelling immunocytochemical study.
Brain Research Bulletin (1992) 28: 557-563
Mendez, I. , Elisevich , K., Naus , C. and Flumerfelt , B. Normalization
ofstriatal proenkephalin and preprotachykinin mRNA expression by fetal
substantianigra grafts. Experimental Neurology (1993) 119: 1-10
Mendez, I. , Elisevich , K. and Flumerfelt , B. GABAergic synaptic interactions
in the substantia nigra . Brain Research (1993) 617: 274-284
Mendez, I. , Sadi , D. and Hong, M. Reconstruction of the nigrostriatal
pathway by simultaneous intrastriatal and intranigral dopaminergic transplants.
The Journal of Neuroscience (1996) 16: 7216-7227
Apostolides C, Sanford E, Hong M and Mendez I. Glial
cell line-derived neurotrophic factor improves intrastriatal graft survival
of stored dopaminergic cells. Neuroscience 1998 ;83 (2): 363-372.
Mehta V, Hong M, Spears J and Mendez, I . Enhancement
of graft survival and sensorimotor behavioral recovery
in rats undergoing transplantation with dopaminergic
cells exposed to glial cell line-derived neurotrophic
factor. Journal of Neurosurgery 1998 ;88 (6):1088-1095.
Research Staff:
Ivar Mendez, M.D., Ph.D., F.R.C.S.(C), Director
Murray Hong, B.Sc.( hon ), M.Sc ., Ph.D., Research Associate
Damaso Sadi , B.Sc., Technician
Residents and Students:
Julian Spears, B.Sc., medical student
Raj Bindlish , M.D., resident in ophthalmology
David MacLean, B.Sc., medical student
Vivek Mehta, M.D., resident in neurosurgery
Costa Apostolides , B.Sc., medical student
Karim Mukhida , B.Sc. student
Website:
Dalhousie University
Division of Neurosurgery Web Site |
HALIFAX,
NOVA SCOTIA | CANADA 