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neurons have to? cell replacement techniques represent? clinical implications for?

have to carry out function for entire life, aren't replaced if damaged. one of the advanced methods by which we can ameliorate dysfunction of lesioned/damaged brain. NDDs like AD, PD for which no adequate medical treatments are avail


5 essential elements of neuronal transplantation?

donor age. host age. vascularization. immunologic factors. target access.


donor age

transplanted tissues survive best when from active stage of embryogenesis


host age

old age drastically reduces survival and fiber outgrowth of graft


vasculrization for neuronal transplantation?

development of adequate blood supply to the graft is one of the most important factors determining graft survival


brain: immunologically? leads to? survival of graft enhanced by?

brain is an immunologic privileged site, leads to delyaed immune response to grafted tissue. by using immunosupressants


target access for neuronal transplantation? where should you always put the graft?

appropriate target area influences graft survival + growth of grafted tissues. always place at terminal area/target site, not the site of cellular origin


3 methods of neuronal transplantation

transplantation of: embryonic tissues, genetically modified cells, polymer-encapsulated cells


transplanation of embryonic tissues: what

solid pieces of tissues in preformed cavity or cell suspension of embronic tissues injected into target area


transplanation of embryonic tissues: 2 advantages + disadvantages

A: good graft survival, regulated release. D: ethical issues, limited avail of fetal tissue


transplanation of genetically modified cells: two cell types? mos commonly used method?

primary cells + immortalized cells. most commonly used: retroviral infection, which yields high levels of transgene incorporation


transplanation of genetically modified cells: 2 advantages + disadvantages

A: trasnplantation of specific genes. no ethical issues. D: unregulated secretion. poor survival of graft


transplanation of genetically modified cells: two classes of genes usually used

grwoth factors: cells genetically modified to produce GDNF, prevents degeneration of DA neurons (for PD). affected NT enzymes: cells genetically modified to produce TH, L-DOPA can ameliorate deficits in PD


transplantation of polymer encapsulated cells: is what? comprises what? what cells?

delivers growth factors/NTs to discrete brain areas. a selective barrier that allows free transport of low but not high MW agents. encapsulated PC12 cells, for animal models of PD


PC12 cells

produces NA + DA. immortalized rat chromaffin cell that releases NA + DA. used for transplantation of polymer encapsulated cells for animal model of PD


transplantation of polymer encapsulated cells: 3 adv? 1 disadv?

use of unmatched tissue, no danger of tumor formation, can be retrieved in case of detrimental effects. D: unregulated secretion


2 animal models of PD

unilateral lesion of nigrostriatal pathway with 6 -hydroxydopamine. bilateral lesion of nigrostriatal pathways with MPTP


6 hydroxydopamine: what lesion induced changes do you see (+ drugs)?

loss of DA neurons triggers drug induced sterotypical rotational behaviour. apomorphine, DA agonist = contralateral while amphetamine = ipsilateral rotation