A novel device for chronic intracranial drug delivery via microdialysis

A system is described for chronic intracranial drug administration in the rat using a modified in vivo microdialysis probe coupled to an Alzet model 2002 osmotic minipump. The results presented demonstrate that this system can be used for the chronic administration of quinolinic acid with minimal non-specific damage. Each pump delivered approximately 225 [mu]l of solution over a period of 19-20 days when tested in vitro. The dialysis units were uniform in function, delivering > 93% of the [3H]quinolinic acid initially loaded into the minipump. For in vivo analysis of this apparatus the dose of quinolinic acid tested produced extensive destruction of the striatum. The present system allows reliable drug diffusion over a relatively large area without pressure injection variability. In conclusion, we have developed a simple and inexpensive technique for administration of drugs into brain parenchyma with substantial advantages over previously used techniques.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29039/1/0000072.pd

A new, simple myelin stain

A new and convenient myelin stain is described. Paraformaldehyde fixed tissue is serially immersed in a nitroblue tetrazolium solution and then in a diaminobenzidine solution. The result is distinct blue staining of myelinated fiber tracts. This technique has advantages over presently used myelin stains.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29768/1/0000106.pd

Chronic intrastriatal quinolinic acid produces reversible changes in perikaryal calbindin and parvalbumin immunoreactivity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31558/1/0000485.pd

Sex differences in the rapid and acute effects of estrogen on striatal D2 dopamine receptor binding

Regional changes in striatal D2 dopamine (DA) receptor binding in castrated (CAST) or ovariectomized (OVX) rats were investigated following administration of a low dose of estradiol benzoate (EB), repeated treatment with EB followed by progesterone, or vehicle. In two separate experiments, there was a significant decrease in striatal D2 DA receptor binding in caudal striatum from OVX, but not CAST rats 30 min after a single injection of EB. In CAST rats, there was a significant increase in striatal D2 DA receptor binding in rostral striatum 4 h after injection of EB. There was no effect of EB plus progesterone treatment in either OVX or CAST rats. In addition, CAST rats had significantly lower D2 DA receptor binding in the lateral region of the rostral striatum than did OVX rats. These results show sexually dimorphic and regionally specific effects of estrogen on striatal D2 DA receptor binding, and a significant sex difference in striatal D2 DA receptor binding in the absence of circulating gonadal hormones. The present findings are discussed in light of previous reports of sex differences in gonadal hormone influences on striatal DA mediated behaviors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31767/1/0000708.pd

Chronic Intrastriatal Dialytic Administration of Quinolinic Acid Produces Selective Neural Degeneration

The excitotoxic hypothesis of Huntington's disease pathogenesis suggests that selective striatal neuronal loss results from excessive activation of striatal excitatory amino acid receptors. Using a microdialysis probe mated to an Alzet 2002 mini-osmotic pump three different concentrations of quinolinic acid or vehicle were administered to the striata of rats over a 3-week period. Animals that received a total of 3.3 [mu]mol of quinolinic acid had significant striatal atrophy that could be attributed to two distinct areas of neuronal loss. First, an area of necrosis surrounding the probe was marked by inflammatory infiltrate and a lack of neurons. In the second region, surrounding the necrotic area, there was a significant reduction in nissl-stained cells, with relative sparing of NADPH-diaphorase-staining neurons. In addition, there was a reduction in cytochrome oxidase staining throughout both of the areas of cell loss. Beyond the area of cell loss, the striatum appeared normal in all respects. The striata of animals that received 880 nmol quinolinic acid appeared identical to those that received vehicle. The striata of animals that received 8.8 [mu]mol quinolinic acid showed severe nonselective atrophy of the striatum and some surrounding structures. We conclude that dialytic delivery of 3.3 [mu]mol quinolinic acid produces an area of neuronal destruction that resembles the selective neuronal loss seen in Huntington's disease. This selective neurodegeneration produced by chronic exposure to quinolinic acid simulates more closely the course of Huntington's disease than previously described methods.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30865/1/0000528.pd