Table 1.

Matching the model to the experimental question.

	In vitro models				In vivo models
	Immortalized cell lines	Primary microglia derived from mixed glial cultures	Ex vivo adult microglia	Organotypic slice cultures	Microglial deficient mice	Chimeric mice
Pros	Large quantities of homogeneous cells economically generated	Large quantities of primary cells are readily obtained; cells differentiated in presence of CNS astrocytes and oligodendrocytes	Differentiated in the presence of intact, functional CNS	Retention of three-dimensional orientation of differentiated CNS neurons, microglia and microglia, easy delivery of cells and molecules	Intact CNS environment	Intact CNS environment, separate manipulation of CNS-resident microglia and peripheral immune cells
Cons	Polarized phenotypes, different lines might yield different assays	Differentiated in the absence of functional neurons, hyperresponsive to pathogenic stimuli	Difficult to obtain sufficient numbers of cells for many assays	Slice ‘wound’ introduces ill-defined inflammatory stimuli to culture system	Incomplete deletion/depletion of only subsets of microglia; difficult to directly measure microglial function	Chimeric mouse methodologies alters vasculature and circulating immune system, difficult to directly measure microglial function
Best use of model	High throughput and first screen assays	Signal transduction assays, molecular manipulation of gene expression and functional consequences of mutational	Assays requiring purified microglia, final assays confirming key observations made in high throughput	Controlled manipulations and measurements difficult to perform in the intact animal (addition of exogenous cells, compounds)	Test of function within intact CNS and in presence of interacting endocrine and immune systems	Test of function within intact CNS and in presence of interacting endocrine and immune systems
How to get access	ATCC	Prepare from fetal or neonatal CNS tissue	Prepare from adult CNS tissue	Prepare from intact CNS	Various animal vendors and research groups	Generate from rodent strains on hand
Refs	[16-18]	[7,8]	[5-7]	[14,15]	[21,22,26-28]	[23-25], Reviewed in [9]