Biology Reference
In-Depth Information
Table 4.3
Neuronal Counts in QA-Lesioned Monkeys Receiving Choroid Plexus Transplants
Treatment
Intact Striatum
Lesion/Implanted
Striatum
Cell Loss
(%)
23965075 1557936
a
QA empty capsule implant
41959437 1309554
43
38615375 6012797
b
QA choroid plexus implant
42031113 409306
8
a
p
0.0001 versus intact striatum.
b
p
0.001 versus QA lesioned striatum.
administration produced a large lesion in both the caudate and putamen nuclei as
shown in NeuN stained sections. The lesion site encompassed much of the caudate
and putamen nuclei before the anterior commissure. With the exception of some
occasional NeuN-positive debris and shrunken neurons, the lesion core was virtually
devoid of NeuN-positive neurons. In contrast, the lesion size was notably reduced in
animals receiving implants of encapsulated CP. In these animals, the core of lesion
was minimal and limited to a small, defined area at the tip of the injection site.
Immediately outside of this central core, but still adjacent to the needle tract, numer-
ous healthy NeuN-ir neurons with dendritic NeuN immunoreactivity were observed.
Stereological counts of NeuN-ir neurons confirmed the gross histological assess-
ment, revealing that, relative to the intact striatum, QA produced a marked loss of
NeuN-ir striatal neurons (43%) that was significantly prevented by prior implants of
encapsulated choroid plexus (only an 8% loss of neurons) (
Table 4.3
). Results from
the volumetric analysis of intact striatum also paralleled the cell counts. Relative
to the intact striatum, animals receiving QA and empty capsules exhibited large
lesions characterized by a 40% decrease in striatal volume (745.508 mm
3
versus
446.825 mm
3
). Conversely, the striatal volume was 672.228 mm
3
in animals previ-
ously implanted with encapsulated CP, which did not differ significantly from the
volume of the intact striatum. Both rodent and monkey studies reveal that implants of
CP can provide trophic influences to degenerating striatal neurons and suggest that
this strategy may ultimately prove relevant for the treatment of HD.
4.11
In Vitro
and
In Vivo
Determinations of the
Effect of Age on CP Function
Given the profound changes in CP function that occur during aging, we conducted
a series of studies to determine if (a) encapsulated CP can be maintained
in vitro
for
extended periods of time without losing its therapeutic activity, and (b) if encapsulated
CP derived from aged animals is less potent than CP from young animals. To begin
to answer the first question, neonatal porcine CP was encapsulated within alginate
microcapsules and maintained
in vitro
for 1, 2, or 7 months
[41]
. The encapsulated
cells remained viable (80%) at all time points and were transplanted unilaterally
into the rat striatum. Seven days later, the same animals received unilateral injections
