Neuroprotective effect of ketamine

There is a great concern in the literature for the development of
neuroprotectant drugs to treat Parkinson’s disease. Since anesthetic
drugs have hyperpolarizing properties, they can possibly act as
neuroprotectants. In the present study, we have investigated the
neuroprotective effect of a mixture of ketamine (85 mg/kg) and
xylazine (3 mg/kg) (K/X) on the 1-methyl-4-phenyl-1,2,3,6-
tetrahydropyridine (MPTP) or 6-hydroxydopamine (6-OHDA) rat
models of Parkinson’s disease. The bilateral infusion of MPTP (100
μg/side) or 6-OHDA (10 μg/side) into the substantia nigra pars compacta
of adult male Wistar rats under thiopental anesthesia caused a
modest (~67%) or severe (~91%) loss of tyrosine hydroxylase-immunostained
cells, respectively. On the other hand, an apparent neuroprotective
effect was observed when the rats were anesthetized with
K/X, infused 5 min before surgery. This treatment caused loss of only
33% of the nigral tyrosine hydroxylase-immunostained cells due to
the MPTP infusion and 51% due to the 6-OHDA infusion. This
neuroprotective effect of K/X was also suggested by a less severe
reduction of striatal dopamine levels in animals treated with these
neurotoxins. In the working memory version of the Morris water maze
task, both MPTP- and 6-OHDA-lesioned animals spent nearly 10 s
longer to find the hidden platform in the groups where the neurotoxins
were infused under thiopental anesthesia, compared to control animals.
This amnestic effect was not observed in rats infused with the
neurotoxins under K/X anesthesia. These results suggest that drugs
with a pharmacological profile similar to that of K/X may be useful to
delay the progression of Parkinson’s disease.