bluuebunny/crossref_metadata_2025 huggingface dataset:
Intraocular Retinal Transplantation: A Review
Authors: Hammer R. M. , Yinon U.
Published: March 2007

This review covers intraocular transplantation of
retinal tissue. This has importance both for
theoretical understanding of retinal and neural
development and for possible future clinical
application.
Transplantation sites have ranged from the
anterior chamber through the retina to the subretinal
space.

Transplanted tissue has ranged from whole
retina to specific retinal layers or specific types of
retinal cells. Both within‐species and inter‐species
transplants have been performed, and donor age has
ranged from embryonic to adult. The ability of
transplanted tissue to be accepted and to differentiate
in host eyes has been studied. The conditions under
which successful transplants are obtained, host‐graft
interactions, and transplantation methodologies have
been explored. Morphological, and to a small extent,
also functional characteristics of the transplants have
been studied.
Survival and Synapse Formation ofTransplanted Rat Rods
Authors: Gouras P. , Du J. , Gelanze M. , Lopez R. , Kwun R. , Kjeldbye H. , Krebs W.
Published: March 2007

Isolated rods enzymatically removed from normal
adult rat retina have been transplanted to the
subretinal space of adult rats with a retinal dystrophy
winich has destroyed almost all the photoreceptors.
These transplanted rods survive for months after
transplantation during which time they form synapses
with other retinal cells. Rod spherules with large
amounts of synaptic vesicles and synaptic ribbons are
found forming discreet contacts with pre‐ and postsynaptic
densities in arrangements closely resembling
those seen in the normal retina.
Estrogen Receptors are Present in Neocortical Transplants
Authors: Pedersen Erik B. , O′Keefe Joan A. , Handa Robert J. , Castro Anthony J.
Published: March 2007

Fetal neocortical tissue was grafted into
neocortical lesion cavities made in newborn rats.
After two weeks survival, in vitro binding of [H3]‐
estradiol to cytosolic preparations provided evidence of estrogen receptors within the transplants. The observed high levels correspond to previous work demonstrating elevated estrogen
receptor levels during the first postnatal week in the rat cerebral cortex.
Successful Xenografts of Second Trimester Human Fetal Brainand Retinal Tissue in the Anterior Chamber of the Eyeof Adult Immunosuppressed Rats
Authors: Epstein Leon G. , Cvetkovich Therese A. , Lazar Eliot , Dehlinger Ky , Dzenko Kirk , del Cerro Coca , del Cerro Manuel
Published: March 2007

Successful xenografting of first trimester human fetal CNS tissue and retina has been reported in the literature. We wished to test the feasibility ofusing the anterior chamber ofthe rat eye to support the development of more mature human fetal xenografts. Here we report on the successful outcome of human brain and retinal transplants. Adult host rats immunosuppressed with cyclosporin A accepted these xenografts and supported their further development. Periodic examination of the host eyes using a direct ophthalmoscope or an ophthalmic slit lamp permitted direct visual monitoring of the health and growth of the transplants. Histologically it was possible to identify neuronal, macroglial, and microglial (macrophage) cell types within the grafts. Mitotic activity and histogenetic differentiation took place. Blood vessels filled with hematic cells were commonly present within the grafts. The walls of these vessels prevented the leakageofhorseradish peroxidase, suggesting the presence of a functional brain‐blood barrier in the graft. These results indicate that it is possible to use a small animal model to study normal and pathological phenomena oniate fetal human neural tissues. Our group has already taken advantage
of the model to achieve HIV infectivity offetal human brain outside the human body.
Effects of Adrenal Medulla and Sciatic Nerve Co‐Grafts in Rats with Unilateral Substantia Nigra Lesions
Authors: Freed William J. , Willingham George , Heim Robert
Published: March 2007

Major limitations of adrenal medulla transplantation
in animal models of Parkinson′s disease
have been the relatively small behavioral
effects and the poor or inconsistent graft survival.
Transplantation of fragments of sural nerve in
combination with adrenal medulla has been reported
to increase the survival of chromaffin cells
in adrenal medulla grafts in primates. In the
present study, the possibility was tested that peripheral
nerve co‐grafts would increase the functional
effects of adrenal medulla grafts in a
6‐hydroxydopamine‐lesioned rat model. Animals
received unilateral substantia nigra lesions, and
subsequently received intraventricular grafts of
adrenal medulla, sciatic nerve, adrenal medulla
plus sciatic nerve, or sham grafts consisting of
medium only. Functional effects of the grafts
were tested using apomorphine‐induced rotational
behavior. The sciatic nerve co‐grafts did
not increase the survival of TH‐immunoreactive
chromaffin cells. The co‐grafting treatment also
did not augment the overall effect of adrenal medulla
grafts on rotational behavior. In the animals
with substantial numbers of surviving chromaffin
cells, however, the animals with sciatic
nerve co‐grafts showed greater decreases in
rotational behavior as compared to the animals
with adrenal medulla grafts alone, even though
the number of surviving cells was not increased.
Expression of Class I and II Major Histocompatibility Complex (MHC) Antigens in the Developing CNS
Authors: Grabowska A. , Lampson L. A.
Published: March 2007

The clinical potential of neural transplantation depends upon the feasibility of allogenenic or xenogeneic transplants, particularly of fetal tissue. This, in turn, is influenced by donor cell expression of MHC antigens. MHC expression in the developing CNS in situ had not been defined. Here, a panel of antibodies was used to define MHC expression in the developing rat embryo.
Intracerebral Implantation of Ionic Synthetic Hydrogels: Effect of Polar Substrata on Astrocytosis and Axons
Authors: Woerly S. , Lavallée C. , Marchand R.
Published: March 2007

In previous studies, hyperporous synthetic
hydrogels of poly(glyceryl methacrylate) or
p(GMA), containing bioadhesive substrates of
collagen, were implanted into rat cerebral tissue
in order to provide systems of oriented guidance
channels for directing the growth of the scar and
axons /28/. In the present study, ionic p(GMA)‐
collagen hydrogels containing polar chemical
groups, either basic amino groups or acidic
carboxyl groups, were evaluated for their
tolerance and their effects on the brain scarring
response and axonal reactivity after long‐term
implantation in the cerebral cortex. In all
animals, the implants were well tolerated.
Although both types of gels influenced the
astroglial reaction near the bioimplant,
hydrogels carrying carboxyl groups had the
strongest influence on the elongation, the
direction and the organization of astrocytic
processes so that a glial matrix could form in
regions of the gel. Extracellular material (e.g.
reticulin) was also deposited into the gels
carrying carboxyl groups. Although cortical nerve fibers .in the surrounding tissue showed a
regenerative response, extending onto or into the
matrices, this behavior seemed to depend more
on the organization of the .astrocytic scar
imposed by the gel than on the type of gel. We
conclude that matrices carrying negatively
charged groups influence favorably the astrocytosis
and the deposition of connective tissue,
and that this approach represents a new avenue
in attempting to modulate the brain scar
formation.
Glutamatergic Control of Striatal Dopamine Release in Normal Rats and 6‐OHDA Rats with Intrastriatal Grafts
Authors: Kondoh T. , Low W. C.
Published: March 2007

Recent animal experiments suggest that transplanted neurons become integrated with the host brain. Neuroanatomical studies have shown that transplanted dopaminergic neurons can form synaptic connections on target cells in the host striatum. Other studies also have shown that grafted neurons not only innervate the host striatum but also receive afferent inputs from neurons of the host. However, little is known about the dynamic regulation of graft‐derived dopamine (DA) release by the host brain. In normal animals, cortical neuronal input to the striatum is carried mainly via glutamate (Glu) neurons. Interactions between DA and Glu in the striatum are shown by in vivo and in vitro studies. Using in vivo microdialysis, the present study was carried out in order to elucidate the effects of glutamatergic agonists and Glu blockade on DA release in the normal striatum and in the striatum of 6‐OHDA rats with dopamine grafts.
Autologous Transplantation of Adrenal Medulla Into the Caudate Nucleus: A Four Year Follow Up Study
Authors: Garcia-Flores E. , Martinez-Campos A. , Farias R.
Published: March 2007

The objective of this study was to determine whether the associated morbidity and mortality of adrenal medulla autologous transplantation into the striatum (open transcortical procedure) justifies this as a safe and effective treatment for Parkinson′s Disease (PD).
Cytological Differences in the Localization of Glucocorticoid Receptor‐Like Imnunoreactivity in the Normal and Transplanted Pituitary Pars Intermedia
Authors: Iturriza Fermlín C. , Dumm César L. A. Gómez
Published: March 2007

Glucocorticoid receptor‐like immunoreactivity
(GCRI) was found in the normal pituitary
pars intermedia (PI) when immunohistochemistry
was used. Since in previous studies we described
two kinds of cells in the denervated
(grafted) PI, i.e., “light cells” (overactive cells
which do not contain detectable melanocyte
stimulating hormone) and “dark cells” (hypoactive
cells which contain the hormone), it was
decided to investigate whether different patterns
of distribution of the receptors could be detected
in the grafted gland when compared with the
intact PI. Intact glands showed the receptors
located in the nucleus. In transplanted glands, it
was observed that light cells showed receptors in
both the nuclei and the cytoplasm; on the other
hand, dark cells displayed them in the nuclei
only, as is the case in all cells of the normal PI.

We had previously interpreted dark cells as
dopamine‐indifferent, whereas light cells were
considered dopamine‐sensitive. The changes in
the distribution of GCR after denervation by
grafting, which only affected the light cells,
support the view of other authors that GCR of.
the pars intermedia are under the influence of
dopamine and reinforce our opinion that dark
cells are dopamine‐indifferent
Peripheral Nerve Transplantation: The Effects of Predegenerated Grafts and Immunosuppression
Authors: Trumble Thomas E.
Published: March 2007

Research involving nerve transplantation has
shown that tissue rejection limits the neurologic
recovery unless the host is immunosuppressed.
This study investigates an alternative to permanent
or temporary immunosuppression using a
rat model with nerve transplants from Brown‐
Norway rat donors to bridge defects in the sciatic
nerve of Lewis rat recipients as these two
inbred strains differ at both major and minor
histocompatibility loci.The specific aim of this
study was to evaluate if predegenerated nerve
grafts decreased the tissue rejection and improved
the neurologic recovery of animals with
allogenic nerve grafts to avoid the problems associated
with either short‐ or long‐term immunosuppression.
The animals in the experimental
groups received cyclosporin‐A, predegencrated
grafts, both, or neither. The predegenerated
grafts were produced by division of the
nerve three weeks prior to grafting to allow for
Wallerian degeneration to occur. The outcome
was assessed by measurements stressing functional
recovery (sensory testing, gait analysis,
joint flexion contracture), studies of muscle recovery
(muscle weight and hydroxyproline concentration),
and histologic studies (axonal
counts and inflammatory reaction). The animals
receiving the predegenerated grafts without cyclosporin
did have an improved recovery (joint
flexion contracture 35° ± 8 ° and hydroxyproline
ratio 1.52 ± 0.16) as compared to the joint flexion contractures and hydroxyproline ratios of
the allograft group of animals without either cyclosporin‐
A or pretreatment and the ungrafted
control group (47° ± 18°, 1.68 ± 0.34, and 53° ±15°
,4.50 ± 0.27, respectively, p < 0.01). However,
all the isograft groups and allograft groups
with cyclosporin‐A, regardless of whether the
graft had been predegenerated or not, had
greater neurologic recovery than the allograft
group with predegenerated grafts but without
cyclosporin‐A by the same parameters (p <
0.01). Allograft groups with short‐term immunosuppression
with cyclosporin‐A did as well
as isograft groups, and isograft groups with predegenerated
grafts did not do any better than
isografts without pretreatment (p <0.01).

Clinical Relevance: Predegenerated nerve allografts
will allow for greater neurologic recovery
than standard nerve allografts avoiding the
complications of immunosuppression, but the
level of recovery is less than that of recipients of
nerve allografts with immunosuppression. Nerve
transplants would avoid the problems of neurologic
deficits at the donor site and allow multiple
large deficits to be treated easily.
The Recovery of the Ultrastructure of Hyperchromic Host Neurons Under the Influence of Fetal Neurotransplants
Authors: Kleshchinov Vladimir N. , Alexandrova Maria
Published: March 2007

Fetal neocortical transplants placed into a
previously prepared cavity in the cortex, of adult
animals inhibited destructive processes in host
neurons surrounding the place of injury. This
was demonstrated by a gradual reduction in the
number of hyperchromic and shrunken host
neurons and the recovery of the ultrastructure of
dystrophic cells which die as a result of
neuronophagia or sclerosis in the absence of the
transplants.
Behavioral Effects of Adrenal Medullary Transplants in Non‐Human Primates
Authors: Dubach Mark
Published: March 2007

Small multiple “ribbon” autografts of intact
adrenal medulla stereotaxically implanted at several
sites throughout the striatum in longtailed
macaques (Macaca fascicularis) have been shown
to contain large amounts of viable glandular tissue
as long as eight weeks after transplantation
/15/. Variations of technique clearly influence
viability/12/. All monkeys were maintained in
specially adapted rotometer cages /30/ so that
24‐hour measurements of activity and directional
bias could be gathered. Lesions induced by intracerebral
injection of 6‐hydroxydopamine in
the substantia nigra produced the expected
chronic decrease in percentage of contralateral
turning in most of the 24 subjects. Animals that
received the longest viable ribbon grafts showed
a reversal of this effect back toward base line,
whereas monkeys whose grafts left little or no
surviving tissue showed no behavioral improvement.
Intrahypothalamically Transected Neurosecretory Axons do notRegenerate in the Absence of Glial Cells
Authors: Dellmann H.-Dieter , Carithers Jeanine
Published: March 2007

Fifteen days after transection of the
hypothalamo‐neurohypophysial tract at the
lateral retrochiasmatic hypothalamic area,
neurosecretory axons had vigorously
regenerated into transplants of explanted
hypophysial neural lobe, to a lesser extent into
sciatic nerve transplants, and least into optic
nerve transplants. Regenerating axons were
always closely associated with the specific glial
cells of these grafts. When these glial cells were
killed by cryotreatment prior to transplantation,
neurosecretory axons did not regenerate into the
abundant extracellular matrix of the
transplants, including persisting basal lamina
tubes in neural lobe and sciatic nerve grafts. The
presence of viable glial cells is a prerequisite for
neurosecretory axon regeneration.
Antinociception Following Implantation of AtT‐20 and GeneticallyModified AtT‐20/hENK Cells in Rat Spinal Cord
Authors: Wu Hope H. , McLoon Steven C. , Wilcox George L.
Published: March 2007

AtT‐20 cells, which produce ß‐endorphin,
and AtT‐20/hENK cells, which are AtT‐20 cells
transfected with a proenkephalin gene, were
implanted in the rat spinal subarachnoid space
in an effort to produce an antinociceptive effect.
Host rats were tested for antinociceptive activity
by standard nociceptive tests, tail flick and hot
plate. Although cell implants had minimal effect
on the basal response to thermal nociceptive
stimuli, administration of the ß2‐adrenergic
agonist isoproterenol produced antinociception
in the cell‐implanted group but not in the
control group. The antinociceptive effect of
isoproterenol was dose‐related and could be
blocked by the opioid antagonist naloxone.
Immunohistochemical analysis of spinal cords
revealed the presence of enkephalin‐negative
cells surrounding the spinal cord of rats
receiving AtT‐20 cell implants, and enkephalinpositive
cells surrounding the spinal cord of rats.
receiving AtT‐20/hENK cell implants. These
results suggest that opioid‐releasing cells
implanted around rat spinal cord can produce
antinociception and may provide an alternative
therapy for chronic pain.
Trained and Amphetamine‐Induced Circling Behavior in Lesioned,Transplanted Rats
Authors: Richards Jerry B. , Sabol Karen E. , Kriek Evelyn H. , Freed Curt R.
Published: March 2007

Rats were trained to turn for water
reinforcement and then were given unilateral 6‐
hydroxydopamine lesions. After lesion, rats
showed deficits in trained turning both contraand
ipsilateral to the side of the lesion, with
contralateral turning more severely impaired.
The lesioned rats were then transplanted with
fetal mesencephalic dopamine tissue into
striatum. A control group of lesioned rats were
sham transplanted. Four weeks after transplant,
1.5 mg/kg D‐amphetamine challenge injections
were used to test the functioning of the
transplants. In the control rats, D‐amphetamine
induced ipsilateral turning; in transplanted rats,
D‐amphetamine slowed the rate of ipsilateral
turning or reversed the direction of
amphetamine‐induced rotation. Only rats which
reversed their, amphetamine‐induced turn
direction after transplant were used for the rest
of the experiment. Trained turning was assessed
at 4, 8, 12 and 16 weeks post transplant.
Transplants did not improve learned
performance at any time post transplant. When
D‐amphetamine was administered in
conjunction with the trained turning sessions, a
low dose (0.12 mg/kg) enhanced contralateral
trained turn rates, without affecting ipsilateral
turn rates. Higher doses of amphetamine
reduced ipsilateral turn rate in the transplanted
animals. The results of this study suggest that
transplants alone do not reinstate performance
of conditioned rotation.
6‐[ 18F]Fluoro‐L‐DOPA and Cerebral Blood Flow in UnilaterallyMPTP‐Treated Monkeys
Authors: Doudet Doris J. , Wyatt Richard Jed , Cannon-Spoor Eleanor , Suddath Richard , McLellan Catherine A. , Cohen Robert M.
Published: March 2007

Intravenous administration of  15O‐labeled
water and 6‐[ 18F]‐L‐fluorodopa were used to
assess abnormal striatal activity in monkeys
after long‐term recovery of unilateral lesions of
the dopaminergic nigro‐striatal system induced
by the neurotoxin MPTP. PET data were
examined in relation to behavioral and
biological parameters. Cerebral blood flow and
6‐[ 18F]‐L‐DOPA uptake were found to be
significantly reduced in the lesioned striatum,
compared to the unaffected side and to normal
controls. There was no correlation between
cerebral blood flow and any of the behavioral
parameters. The uptake rate constant of  18F‐DOPA from blood to striatum and the ratios of
striatum to occipital areas were highly
correlated to the concentrations of homovanillic
acid in the cerebrospinal fluid of the same
animals but not to the rotational behavior. This
MPTP‐inducedmodei of striatal dopamine
deficiency in primates presents similarities with
idiopathic Parkinson′s disease and may be used
to evaluate the effects of dopaminergic lesions
and transplants on brain function.
Effect of Fetal Striatal and Astrocyte Transplants into UnilateralExcitotoxin‐Lesioned Striatum
Authors: Lu Sunny Y. , Pixley Sarah K. , Emerich Dwaine F. , Lehman Michael N. , Norman Andrew B.
Published: March 2007

Studies have suggested that neurotrophic
mechanisms may underlie transplant‐induced
functional recovery. Astrocytes have been
reported to be a source of neurotrophic factors.
The present study examined the possible role of
cultured astrocytes in promoting recovery of
apomorphine‐induced rotation behavior in rats
with unilateral kainic acid (KA) lesions of the
striatum. Five weeks after the lesions, one group
of rats received fetal striatal tissue (E17)
transplants, another group received transplants
of cultured astrocyte suspension, and the
remaining rats received sham transplants and
served as controls. Apomorphine‐induced
rotation behavior was tested 4 weeks after the
KA lesions, and 5 and 10 weeks following the
transplantation. The KA‐induced rotation
behavior was reduced by the striatal transplants
but not by the cultured astrocyte transplants 5
and 10 weeks following the transplantation.
Histochemicai analysis indicated that the striatal
transplants had survived and grown and
contained neurons and glia with similar
morphology to those in the host brain.
Immunocytochemical analysis of the astrocyte
transplant sites revealed heavy glial fibrillary
acidic protein and OX‐42 staining in the
transplant areas, suggesting that the
transplanted astrocytes may have survived in the host brain. Although fetal striatal
transplants can ameliorate apomorphine‐induced
rotation behavior, transplants of
astrocytes alone may not be sufficient to reverse
the functional deficits produced by KA lesions.
Adrenal Medullary Grafts Restore Olfactory Deficits andCatecholamine Levels of 6‐OHDA Amygdala Lesioned Animals
Authors: Fernández-Ruiz Juan , Guzmán Rubén , Martínez María Dolores , Miranda María Isabel , Bermúdez-Rattoni Federico , Drucker-Colín René
Published: March 2007

Aside from motor and cognitive deficits,
Parkinson patients also manifest a little‐studied
olfactory deficit. Since in Parkinson′s disease
there is a dopamine depletion of the amygdala
due to mesocorticolimbic system degeneration,
we decided to test olfactory and taste
performance of 6‐OHDA amygdala lesioned
rats, as well as the possible restoration of either
function with adrenal medullary transplants.

Two 6‐OHDA lesioned groups and one
control group were tested in the potentiation of
odor by taste aversion paradigm. On taste
aversion none of the groups showed any
impairment. In contrast, the 6‐OHDA lesioned
rats showed a marked impairment in olfactory
aversion. At this point, one of the lesioned
groups received a bilateral adrenal medullary
graft within the lesioned area. After two months,
all groups were submitted again to the
behavioral paradigm. Taste remained
unaffected, but the lesioned only group did not
recover either olfactory aversion or normal
catecholamine levels. The grafted group, on the
other hand, restored olfactory aversion and
catecholamine levels. It can be concluded from
this study that catecholamine depletion of the
amygdala is sufficient to produce a selective
olfactory deficit, not accompanied by taste
impairments, and that such a deficit can be
reversed by adrenal medullary transplants,
which in turn restore catecholamine levels.
Age‐Related Loss of GABA‐Positive and GABA‐Negative Neurons in Neocortical Transplants
Authors: Bragin A. , Takács J. , Vinogradova O. , Gogelia Kh. , Hámori J.
Published: March 2007

The numerical density of GABA immunopositive and GABA immunonegative neurons was quantitatively determined in 0, 12, 30 and 90 day‐old neocortical transplants, derived from E17 rat embryos and transplanted into adult hosts. It was found that the original, very high neuronal density in the fetal transplant declined steadily after transplantation to the somatosensory cortex of adult rat. The decline in numerical density of GABA‐positive neurons, however, was disproportionately larger than that of GABA‐negative nerve cells: At 90 days the proportion of GABA‐positive cells was 2.3% (in contrast to the 11.8% in the adult host cortex). The density of GABA‐negative neurons, on the other hand, remained slightly higher than comparable values in the control cortex. The decline in density Of GABA‐positive neurons was continuous until the 90th post‐transplantation day, while final, close to normal density values of GABA‐negative nerve cells were already reached in 30 day‐old grafts, with no significant change afterwards.
Astroglial Induction of in vivo Angiogenesis
Authors: Suárez I. , Bodega G. , Rubio M. , García-Segura L. M. , Fernández B.
Published: March 2007

A purified population of astrocytes was
prepared from embryonic rat hypothalamus.
These cells were transplanted into the cerebral
cortex of adult rats with survival time of 5 days
and studied by glial fibrillary acidic protein
(GFAP) immunohistochemistry and electron
microscopy. A progressive gradation from the
edges of the implant to the intact host tissue was
observed in relation to the vascularization
process. The regenerating tissue showed cells
with cavities resembling capillary central lumens
and their cytoplasms revealed gold. particles
when they were immunostained for electron
microscopy. Dark processes were seen in
capillary‐like lumens and, on other occasions,
evaginations of endothelial cells were in contact
with astroglial processes. These findings lead us
to suggest, that capillary‐like structures might
develop from cavitated astroglial cells, which
would permit the migration of endothelial cells
into their lumens. Astroglial‐endothelial
interactions persist until endothelial cells are
morphologically differentiated. One possible
interpretation of the present data is that
astrocytes might participate directly and
actively in the regulation of capillary formation.
Long‐Term Effects of Axotomy on β‐Tubulin and NF Gene Expression in Rat DRG Neurons
Authors: Jiang Yuan Qing , Pickett Judith , Oblinger Monica M.
Published: March 2007

To compare the long‐term recovery of gene
expression in dorsal root ganglion (DRG)
neurons under conditions of regeneration vs.
non‐regeneration, Northern blotting and in situ
hybridization were used to assess steady‐state
neurofilament (NF) and beta tubulin mRNA
levels 12 weeks following axonal injury. Adult
male rats sustained either a crush lesion of the
mid‐sciatic nerve (regeneration occurs), or a cut
lesion of the sciatic nerve combined with ligation
of the proximal nerve stump and removal of a
large segment of the distal nerve (regeneration
does not occur). In the latter case, neuroma
formation physically prevented axonal regeneration.
Results of Northern blotting of total RNA
obtained from the DRG indicated that NF‐L and NF‐Μ
mRNA levels had largely returned to
control levels at 12 weeks following crush
axotomy but were still substantially depressed
following cut/ligation injury of the sciatic nerve
at that time. in situ hybridization studies
indicated that both crush and cut/ligation
axotomy resulted in significantly lower NF‐L
mRNA levels in large‐sized (>
1000  μm2) DRG
neurons at 12 weeks post‐axotomy. Discrepancies
in the conclusions from Northern
blotting and in situ hybridization experiments
were also noted in the case of tubulin
mRNA changes at long intervals after axotomy. in situ
hybridization data derived from the large‐sized
DRG neurons using a coding region β‐tubulin
cDNA (which recognizes both βΙΙ
and βΙΙΙ
mRNAs) showed complete recovery of β‐tubulin
mRNA levels in surviving, large‐sized DRG
neurons after crush axotomy, but significantly
elevated tubulin mRNA levels in surviving large
DRG cells at 12 weeks after cut/ligation
axotomy. In contrast, Northern blotting results
indicated that βΙΙ‐tubulin mRNA levels in the
crush axotomy condition remained elevated
relative to control while they were substantially
lower than control in cut/ligation axotomy
samples. Results from analysis of βΙΙΙ‐tubulin
mRNA changes were not conclusive. The lack of
complete correspondence in the results from the
two different methods of analysis of mRNA
changes (blotting vs. in situ) is likely to be due to
selective loss of large‐sized DRG neurons in the
long‐standing cut/ligation injury condition. This
would influence results from blotting data,
where RNA is derived from the DRG as a whole,
more so than in situ hybridization experiments
which specifically focus on the surviving largesized
neurons. Overall, data from these
experiments indicate that altered patterns of
gene expression remain in the DRG for long
intervals after axonal injury, whether or not
axonal regeneration has been successful.
However, recovery of “normal8221; patterns of
cytoskeletal gene expression in the DRG is
considerably more complete after crush injury
than after cut/ligation injury.
Effects of Nerve Growth Factor Infusion on Behavioral Recovery and Graft Survival Following Intraventricular Adrenal Medulla Grafts in the Unilateral 6‐Hydroxydopamine Lesioned Rat
Authors: Bergdall Valerie K. , Becker Jill B.
Published: March 2007

NGF was infused into the lateral ventricle of rats with unilateral 6‐OHDA lesions of the substantia nigra along with adrenal medulla or control grafts. Treatment effectiveness, as measured by amphetamine‐induced turning behavior, indicated that there were no significant differences between treated and control groups in spite of the survival of tyrosine hydroxylase (TH) immunoreactive grafts. Furthermore, adrenal medulla graft survival was not dependent on NGF infusion. These results indicate that TH‐posttive graft survival is not correlated with behavioral recovery as assessed by amphetamine‐induced turning. These results differ from studies which utilized apomorphineinduced turning as a measure of behavioral recovery. We propose that adrenal medulla graft survival alone is not sufficient to promote behavioral recovery in the 6‐OHDA lesioned rat.
Ultrastructural Circuitry in Retinal Cell Transplants to Rat Retina
Authors: Zucker Charles L. , Ehinger Berndt , Seiler Magdalene , Aramant Robert B. , Adolph Alan R.
Published: March 2007

The development of five transplants of fetal
retinal tissue to adult rat eyes was examined
with the electron microscope. The transplants
were of 9 to 10 weeks total age after conception
in four cases and 20 weeks in one case. They
were at stage E15 when transplanted.
Transplants developed in both the epiretinal and
subretinal spaces.

The transplants were heterogeneously
developed with some parts showing almost
normal differentiation and others little.
Subretinal transplants examined in this study
were more developed than epiretinal grafts.
Photoreceptor cells developed both inner and
outer segments. Their synaptic terminals
possessed output ribbon synapses with
postsynaptic processes similar to those seen in
normal retinas. In regions corresponding to the
inner plexiform layer, the adult complement of
synapses was seen, including advanced features
such as serial synapses as well as reciprocal
synapses at bipolar cell dyads. Incompletely
differentiated synapses of both the amacrine and
bipolar cell types were often observed, especially
in the rat epiretinal transplants. Ganglion cell
processes could not be identified with certainty.

Although transplant cells were adjacent to
host photoreceptor cells and pigment
epithelium, obvious specializations or
interactions were not observed. The experiments
suggest that embryonic rat retinal cell
transplants develop most or perhaps all of the
structural components and neuronal circuitry
necessary to transduce light and process some
visual information.
Ultrastructural Signs of Regenerative‐Degenerative Processes in Long‐Term Dentate Fascia Grafts
Authors: Zhuravleva Z. N.
Published: March 2007

An ultrastructural investigation of embryonic
(E20) dentate fascia grafts transplanted into an
acute cavity in the somatosensory neocortex of
adult rats revealed a continuous dynamic state
of the tissue nine months postgrafting. The grafts
consisted mainly of typical granular cells with
some admixture of hippocampal pyramidal
neurons and polymorph hilar cells with a
normal, mature ultrastructure. Many features of
the transplanted tissue suggested continuing
development and growth. Dendritic branches
with growth tips, axonal growth cones, synaptic
boutons with growth vesicles, immature myelin
sheaths and myelin‐producing cells were observed.
In contrast, ultrastructural signs of degeneration
were present in some axons, and, less often, in
dendrites. These processes, as well as some of the
terminal synapses, contained various amounts of
lysosomes and lipofuscine granules. In many
such terminals the signs of degenerative change
were combined with the presence of multiple
mitochondria, polymorph vesicles and tubular
reticulum, indicating simultaneous reparative
processes. It is suggested that continuous
recycling of neuronal processes occurs in longterm
dentate grafts. This morphological instability
nay depend on the paucity of synaptic targets
within the dentate tissue transplanted with a
minimal quantity of hippocampal pyramidal
cells and on the limitation of the afferent input.
However, the observed features of the grafted
dentate tissue are not qualitatively different
from those observed in normal dentate with its
protracted development and active compensatory
reorganization.
Neuropathological Sequelae of Long‐Term Allogeneic and Syngeneic Neural Transplantation into the Hippocampus
Authors: Patel Sanjay N. , Kershaw Tim R. , Williams John , Gray Jeffrey A. , Lantos Peter L. , Sinden John D.
Published: March 2007

The long‐term fate of multiple intrahippocampal
allogeneic transplants of fetal basal
forebrain tissue was studied in neonatally
tolerised and immunised groups of rats with
lesions of the fimbria‐fornix. Despite the good
survival of the allografts in all groups,
unexpected transplant‐associated host hippo‐campal
neuropathology was discovered 12
months after transplantation, which consisted of
(i) CA1 cell degeneration and (ii) abnormal
accumulations of phosphorylated neurofilaments
in neuronal perikarya and axonal swellings only
within the host hippocampal neuropil and not of
the transplanted tissue. This neurofilament
abnormality, identified by RT97 immunohistochemistry,
was significantly greater in the
transplanted rats compared to the non‐grafted
lesion‐only and sham‐lesioned rats (p<0.01)
. The
same type of neurofilament abnormality was
again observed in a second, separate experiment
using unilateral and bilateral syngeneic and
allogeneic transplants. The neuropathology was
significantly (p<0.05)
greater in the transplanted
side of the unilateral transplanted rats
compared to the non‐transplanted lesion‐only
control side of the same animals, showing that
transplantation per se was a major factor
involved in the pathogenesis of this neuropathology,
irrespective of the type of transplant
(syngeneic or allogeneic). In addition, a small
degree of neurofilament abnormality was also
found within the transplants in the second
experiment, but not in the first. The results show
that, under certain conditions, specific local
neuropathological damage to the surrounding
host neural tissue can develop in long‐surviving
allografted and syngrafted animals.
Isolation of Enteric Ganglia from the Myenteric Plexus of Adult Rats
Authors: Jaeger Christine B.
Published: March 2007

Enteric neurons and glia cells were isolated
from adult Sprague Dawley rats. A procedure is
described using a combination of microdissection
and mechanical dissociation after
enzyme treatment which yields large numbers of
cell clusters suitable for tissue culture and
grafting into the injured spinal cord. Differentiated
enteric ganglia remained viable for at
least 5 days in vitro Cultured neurons expressed
histochemical reactivity for acetylcholinesterase
and nicotinamide adenine dinucleotide phosphate
diaphorase. Nestin positive glia, which
represented a population of non‐myelinating
enteric Schwann cells, could also be identified in
cultures maintained 5 days or longer in vitro.
The myenteric plexus of adult rats can provide a
readily available source of neurons and
Schwann cells for grafting to the central nervous
system.
Origin of Afferent Projections into Bovine Chromaffin Cell Implants in the Rat Periaqueductal Gray Determined by Retrograde and Anterograde Tracing
Authors: Ortega John D. , Sagen Jacqueline , Pappas George D.
Published: March 2007

We have previously described long‐term
survival of isolated bovine chromaffin cell
suspension grafts in the periaqueductal gray of
adult rats. Electron microscopic analysis of the
graft sites revealed synapses on the transplanted
chromaffin cells. The origin of these synapses is
not known, but they are probably derived from
the host since the initial grafts were suspensions
of chromaffin cells that were essentially free of
other cell types.

In order to determine the origin of the
observed synapses, retrograde and anterograde
tracer analyses, were performed on grafted rats
at 4 and 8 weeks after transplantation.
Following injection of the retrograde tracer
(Fluoro‐Gold) into graft sites, four major host
sites were labeled: hindbrain reticular
formation, substantia nigra, lateral
hypothalamus, and cingulate cortex. Injection of
anterograde tracer (rhodamine‐conjugated
dextranamine) into the substantia nigra, lateral
hypothalamus, and cingulate cortex produced
labeled fibers and terminals in and around 4
and 8 week old chromaffin cell graft sites. An
increase in both the number of retrogradely
labeled cells, as well as in the density of
anterogradely labeled fibers and terminals within
the graft site, was observed from 4 to 8
weeks.

This study shows that graft innervation from
the host is primarily from areas that normally
project afferent fibers to the periaqueductal
gray. The increase in labeled fibers, and
terminals over 8 weeks suggests that de novo
synapse formation on grafted bovine chromaffin
cells is a continuous process that is dependent on
the regenerative capacity and plasticity of the
host neuronal network and the grafted bovine
chromaffin cells.
Effects of Intraventricular Locus Coeruleus Transplants on Seizure Severity in Genetically Epilepsy‐Prone Rats Following Depletion of Brain Norepinephrine
Authors: Clough R. W. , Browning R. A. , Maring M. L. , Statnick M. A. , Wang C. , Jobe P. C.
Published: March 2007

Audiogenic seizures (AGS) in genetically
epilepsy‐prone rats (GEPR) of the moderateseizure
substrain (GEPR‐3s) were investigated
to determine whether norepinephrine (NE)
depletion induced by 6‐hydroxydopalnine (6‐OHDA)
microinfusion into the locus coeruleus
(LC) could alter the efficacy of intraventricular
NE tissue grafts in promoting reductions in
seizure severity in AGS. GEPR‐3s were
stereotaxically infused with 6‐OHDA
(4μg/side/rat), or vehicle into the region of the
LC. Following 6‐OHDA treatment all animals
were subjected to 3 AGS tests. GEPR‐3s seizure
severities were increased in 39.5% of the
animals after microinfusion of 6‐OHDA into the
region of the LC. Following the third AGS test,
each rat was stereotaxicaily implanted with 17
gestational day rat fetal tissue obtained from the
dorsal pons and containing the primordia of the
LC or with tissue obtained from the neocortex
or were sham‐grafted. Subsequent to grafting,
rats were subjected to 3 additional AGS tests.
53% (10/19) of 6‐OHDA treated GEPRs showed
a significant reduction in seizure severity
following transplantation of fetal LC tissue. In
contrast, only 20% (1/5) of GEPRs infused with
saline rather than 6‐OHDA showed, a reduction
of seizure severity following fetal LC
transplantation. NE content in the cortex and
pons/medulla was decreased by 78% and 46%
respectively following 6‐OHDA microinfusion
into the LC. Prominent grafts with numerous
TH positive neurons and neurites were present
within the third ventricle of grafted animals,
while cortex grafts contained no TH
immunostained structures. These findings
suggest that the efficacy of fetal LC tissue to
promote reductions in seizure severity in GEPRs
is increased following depletion of central NE by
microinfusion of 6‐OHDA.
Effects of Cultured Adrenal Chromaffin Cell Implants on Hindlimb Reflexes of the 6‐OHDA Lesioned Rat
Authors: Pulford Bruce E. , Mihajlov Andrea R. , Nornes Howard O. , Whalen L. Ray
Published: March 2007

The effects of implantation of cultured
adrenal medullary cells on the recovery of
neurotransmitter specific reflex activity were
studied in the rat spinal cord using electrophysiological
testing methods. Cell suspensions
of cultured neonatal adrenal medullary
chromaffin (AM) cells (which produce
catecholamines), or Schwann (Sc) cells (controls)
were implanted into the lumbar region of the
spinal cord 2 weeks after catecholamine (CA)
denervation by intracisternal injection of 6‐hydroxydopamine
(6‐OHDA). All cells were
taken from 7 day neonates and cultured for 10
days in the presence of nerve growth factor
(NGF). Three months after implantation, the
extent of implant‐associated recovery of reflex
activity was determined by measuring electromyogram
(EMG) activity and force associated
with the long latency component of the hindlimb
withdrawal reflex (which is CA modulated).
After the electrophysiological testing, rats were
anesthetized, and the spinal cords were rapidly
removed and frozen. Spinal cords were sectioned
longitudinally, and implanted cells were
visualized using glyoxylic acid techniques.
Labelled sections were examined to determine
cell survival. Results indicate that 1) chromaffin
cells survive for 3 months in the segments of the
cord into which they have been implanted and
2) rats implanted with AM cells have
significantly more forceful withdrawal reflexes
than those that received Sc cells or received no
implant after lesioning.
Cerebellar Culture Models of Dendritic Spine Proliferation After Transplantation of Glia
Authors: Seil Fredrick J.
Published: March 2007

Studies of Purkinje cell dendritic spine proliferation after transplantation of cytosine arabinoside (Ara C) treated organotypic
cerebellar cultures with glia and granule cells, either separately and in combination, were reviewed. Exposure of cerebellar explants to
Ara C for the first 5 days in vitro results in the destruction of granule cells, the only excitatory cortical neurons, and oligodendroglia, and
functionally compromises surviving astrocytes so that they do not appose neuronal membranes. In the absence of granule cells, there is a sprouting of Purkinje cell recurrent axon collaterals, the terminals of which project to and form heterotypical synapses with Purkinje cell
dendritic spines, which are usually occupied by terminals of granule cell axons (parallel fibers). After this reorganization has been achieved, the explants can be transplanted with the missing elements to induce a second round of reorganization, with approximate restoration of
the usual interneuronal relationships. Addition of both granule cells and glia resulted in a proliferation of clusters of Purkinje cell
dendritic spines, which formed synapses with axon terminals of transplanted granule cells, and as synapse formation progressed, the spine
clusters became reduced. Transplantation of Ara C‐treated cultures with glia alone resulted in a proliferation of clusters of Purkinje cell
dendritic spines, but in the absence of granule cells the spines remained unattached, and the clusters persisted throughout the period of
observation. Purkinje cell dendritic spine proliferation was induced by exposure of Ara C‐treated cultures to astrocyte‐conditioned
medium. When Ara C‐treated cerebella cultures were transplanted with granule cells in the absence of functional glia, parallel fiber‐
Purkinje cell dendritic spine synapses formed, but no clusters of Purkinje cell dendritic spines were observed. These findings suggest that
Purkinje cell dendritic spine proliferation is induced by an astrocyte‐secreted factor, resulting in an expansion of postsynaptic sites
available for synaptogenesis.
Regional Differences of Serotonin‐Mediated Synaptic Plasticity in the Chicken Spinal Cord With Development and Aging
Authors: Chen Ling , Hamaguchi Kayoko , Hamada Shun , Okado Nobuo
Published: March 2007

Previous studies in our laboratory /3,17/ have demonstrated that serotonin (5‐HT) appears to have a trophic‐like effect in enhancing synapse formation and maintenance in both the developing and the adult central nervous system. In the present study, we focused on age‐related changes in the density of the axosomatic and axodendritic synapses and the number of 5‐HT‐positive fibers in the chicken spinal cord, with special reference to differences between the ventral (laminae VII and IX) and the dorsal (lamina I) horn. At 1 week posthatching (PIW),
a transient overproduction of synapses and 5‐HT‐immunoreactive fibers occurred in lamina IX; all parameters had returned to their initial levels by 1 month post‐hatching (PIM). The density of synapses further decreased by about 40% between P6M and P2Y (2 years
posthatching). Although the magnitude of the transient increase in lamina VII was less than that in lamina IX, the changing pattern of the
synapses and the 5‐HT‐positive fibers was similar in both regions. In the ventral horn, thin 5‐HT‐positive fibers were most prominent at
P1W and then decreased with development; thin 5‐HT‐positive fibers were still found at P6M but had almost disappeared by P2Y. By contrast, at
P2Y the density of the synapses and the 5‐HT‐positive fibers in the dorsal horn was even higher than that of younger animals.

Reduction of 5‐HT levels in P2Y‐old chickens by p‐chlorophenylalanine (pCPA) administration decreased the synaptic density in lamina I but not in lamina IX. The results of this study demonstrate that 5‐HT‐mediated synaptic plasticity is markedly different in the ventral and dorsal horns of the aged chicken. In the ventral horn, synaptic plasticity reached a maximum at about P1W, remained stable in the young‐adult period, and then finally disappeared in the aged chicken. Conversely, the results suggest that in the dorsal horn, 5‐HT fibers continue to mediate the trophic influence on synaptic plasticity even in the old chicken.
Morphometric Analysis of Hippocampal Pyramidal Neurons in situ and in Grafts Developing in the Anterior Eye Chambers of Young and Aged Wistar Rats
Authors: Zhuravleva Z. N. , Saifullina V. N. , Zenchenko C. I.
Published: March 2007

We performed a morphometric analysis of the somatic and nuclear areas in the pyramidal neurons of the hippocampal fields CA1 and CA3 in situ and in grafts developing for six weeks in the anterior eye chambers of young (3‐to‐9 wk.) and of aged (18‐to‐19.5 mos.) Wistar rats. The mean areas of the CA1 pyramidal somata and nuclei were significantly decreased in the aged animals in situ. The mean parameters of the CA3 pyramidal neurons were not changed, although their distribution was different (bimodal versus unimodal in the young animals). In both groups of recipients, the areas of CA1 neurons and of their nuclei were significantly larger in the grafted tissue than those found in situ. The areas of CA3 neurons did not show any difference in aged recipients and demonstrated only slight hypertrophy in young recipients. We concluded that the area sizes of the pyramidal cell bodies and nuclei in CA1 neurons are more sensitive than those of CA3 neurons to both aging and transplantation. The age of recipients did not significantly influence the growth and development of grafted pyramidal cells.