bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of an Experimental Cortical Network: ii) Connections of VisualAreas 17 and 18 After Neonatal Injections of Ibotenic Acid
Authors: Innocenti G. M. , Berbel P.
Published: March 2007

Lesions of cortical areas 17 and 18 were produced
in newborn kittens by local injections of
the excitotoxin ibotenic acid. In the adult this
results in a microcortex which consists of superficial
layers I, II and III, in the absence of granular
and infragranular layers. Horseradish peroxidase,
alone or wheat germ agglutinin conjugated,
was injected in the microcortex or in the
contralateral, intact areas 17 and 18. The microcortex
maintains several connections characteristic
of normal areas 17 and 18 of the cat. It receives
afferents from the dLGN, and several visual
areas of the ipsilateral and contralateral
hemisphere. However, it has lost its projections
to dLGN, superior colliculus, and, at least in
part, those to contralateral visual areas. Thus some parts of the microcortex receive from, but
do not project into, the corpus callosum. In addition,
the microcortex maintains afferents from
ipsilateral and contralateral auditory areas AI
and AII which are normally eliminated in development.
Photoreceptor Cell Rescue at Early and Late RPE‐Cell Transplantation PeriodsDuring Retinal Disease in RCS Dystrophic Rats
Authors: Sheedlo Harold J. , Li Linxi , Turner James E.
Published: March 2007

Maximal PRC rescue was affected by RPE‐cell transplantation in retinas of RCS dystrophic rats at early stages of the retinal disease, while little or no rescue was detected when transplantation was performed at late time periods.
Behavioral Effects of Gangliosides: Anatomical Considerations
Authors: Emerich Dwaine F.
Published: March 2007

Gangliosides are endogenous sialic acid
containing glycospingolipids which are highly
concentrated in the central nervous system.
Although they were first characterized over 40
years ago, the function(s) played by this unique
class of lipids remain largely unknown.
Gangliosides have been suggested to play a
prominent role in both normal and abnormal
developmental processes. In addition, several
lines of convergent evidence have indicated that
gangliosides exert pronounced trophic effects
following damage to peripheral and central
nerves. Gangliosides have been shown to (1)
enhance cell survival and outgrowth in cultured
and developing neurons; (2) promote the
regeneration of damaged peripheral and central
nerves, and (3) facilitate behavioral recovery by
altering the pattern, extent and persistence of the
biochemical, morphological and behavioral
changes induced by neural trauma. Little is
known, however, concerning the neurobiological
mechanisms which subserve the. behavioral protection afforded by ganglioside treatment.
This review focuses on the evidence suggesting
that gangliosides mediate functional recovery by
minimizing primary or secondary cell loss or
promoting the regeneration or sprouting of
damaged central nerves subsequent to injury.
An understanding of the mechanisms, by which
gangliosides produce their effects may lead to the development of more efficacious and rational primary or adjunct pharmacological treatments
for central nervous system disorders.
Microencapsulated Bovine Chromaffin Cells In Vitro: Effect of Density and Coseeding with a NGF‐Releasing Cell Line
Authors: Winn S. R. , Tresco P. A. , Zielinski B. , Sagen J. , Aebischer P.
Published: March 2007

Immobilization of discrete cell clusters
within a partially crosslinked matrix prevents
reaggregation of primary tissues and may
provide a means for long‐term maintenance of
encapsulated cells. Dissociated bovine adrenal
chromaffin (BAC) cells were suspended
throughout crosslinked polyanionic microspheres
previously shown to be selectively
permeable. Microcapsules approximately 500
µm in diameter were seeded with: 1) three
different densities of BAC cells; and 2) BAC
cells suspended in Matrigel ®
or coseeded with a
genetically modified nerve growth factor (NGF)‐
releasing fibroblast cell line. Each group was
analyzed in vitro at 1, 4 and 8 weeks for
spontaneous and potassium‐evoked release of
catecholamines, and maintained in vitro for up
to 12 weeks for morphological observations.
Over time, release of norepinephrine (NE) and
epinephrine (EPI) diminished, while dopamine
(DA) remained constant from the monoseeded
capsules. In the coseeded group, an increase in
potassium‐evoked release of DA was observed
from 1 to 4 weeks, and remained at that level up
to 8 weeks. Encapsulated chromaffin cells
retained a rounded morphology typical of
undifferentiated cells. Intact chromaffin cells
with well preserved and abundant secretory granules were observed ultrastructurally after 4
weeks in vitro. Small neurites from the chromaffin
cells in the coseeded group were observed at 4
weeks with light microscopy, and up to 12 weeks
with electron microscopy. Under static incubation
conditions, 1 mM D‐amphetamine resulted
in a significant increase in the output of NE and
DA from the coseeded capsules 8 weeks postimplantation,
as compared to microcapsules
loaded with chromaffin cells alone. Encapsulation
within an immobilization matrix allows
manipulation of the internal environment,
thereby providing the ability to pre‐treat cells
with various factors in a non‐invasive manner,
which may enhance long‐term cellular viability.
Fetal Brain Transplantation in Kainic Acid Lesioned Caudate Nucleus of Adult Rats
Authors: Tandon P. N. , Kumar V. Mohan , Verma Suneeta , Gopinath Gomathi , Shetty Ashok Kumar
Published: March 2007

This study confirmed that bilateral kainie acid (KA) injection at the caudate produces aphagia and adipsia in rats. The reduction in food and water intake was fatal after a higher dosage of the drug. To test the effect of transplantation on. the mortality, rate, KA was first injected in the left caudate, in one set of rats. After a gap of three days, fetal striatal tissue was unilaterally transplanted at this lesioned site, along with a second injection of KA in the right caudate. Successful transplantation, as ascertained morphologically, did not significantly alter the mortality rate. The morphometric study revealed that the neurons of the transplant were larger in size, and their numerical density lower than those of the caudate of normal rats. Only very few neurons of the transplant developed functional connectivity with the host, as demonstrated by electrophysiological studies.
Transplantation of Human Neuroblastoma Cells, Catecholaminergic and Non‐Catecholaminergic: Effects on Rotational Behavoir in Parkinson′s Rat Model
Authors: Manaster Jacob S. , Feuerman Tony , Reynolds C. Patrick , Markham Charles H.
Published: March 2007

Cultured human catecholaminergic and noncatecholaminergic
donor cells were used in
neural transplantation experiments in a rat
model of Parkinson′s disease. Using two different
human catecholaminergic neuroblastoma cell
lines, one control non‐catecholaminergic neuroblastoma
cell line, and one sham control (tissue
culture medium), transplants were made into the
striatum using a modified Ungerstedt
hemiparkinsonian rat model. Significant
decreases in apomorphine‐induced rotational
behavior were produced by two of three
catecholaminergic cell lines. Grafted cells staining
positively for tyrosine hydroxylase (TH) and
catecholamine fluorescence indicated viable catecholamine
activity in the two cell lines which produced
reductions in rotational behavior.
Catecholamine fluorescence was not detected in
either of the two controls. These data suggest a
link between catecholamine secretion by transplanted
cells and motor improvement using a rat
rotational behavior model.
Fetal Rat Cerebellar Fragment Transplantation into Adult Rat Forebrain Lesion Cavities
Authors: Chopko Bohdan W. , Voneida Theodore J.
Published: March 2007

Fragments of fetal rat cerebellar tissue were
grafted into forebrain cortical lesion cavities of
adult rats. After a survival ranging from 12‐151
days, no graft was found to fill the cavity
completely. Large neurons, occasionally grouped
into nests, were identifiable from the 22nd day.
Myelinated graft fibers, first seen at 32 days,
failed to enter host brain. Although grafts
demonstrated elements resembling cerebellar
tissue, overall organization did not resemble that
of the cerebellum.
Viable Adrenal Medullary Transplants in Non‐Human Primates: Increasing the Number of Grafts
Authors: Dubach Mark
Published: March 2007

The robust survival of stereotaxic adrenal
medullary autografts in monkey brain parenchyma
depends heavily on technique/11/. One
aspect of technique critical for clinical applications
of CNS grafting is the problem of spreading
treatment effects throughout large regions in a
primate brain. Stereotaxic placement of a large
number of grafts, which would address this problem,
would require that later grafts retain the
capacity for viability over a long period of time
during the surgery, while earlier grafts are being
made. In the present experiments involving 12
longtailed macaques (Macaca fascicularis), some
grafts remained in medium 2.5 h before being
transplanted, without apparent loss of viability.

clinically sufficient distribution of graft tissue
would also require a large number of separate
grafts to be derived from one adrenal medulla.
One method for subdividing the gland might be to
cut it into numerous very small pieces, but various
dicing techniques described in this report
have yielded little viable graft tissue. On the
other hand, the number of ribbon grafts of the
original dimensions available from a single gland
is rather small; adrenal ribbons of the original
dimensions were therefore further dissected.
Half‐length and half‐width ribbons were successful,
but less so than full‐size ribbons in terms of
proportionate viability. An assay of behavioral
effectiveness, applied to all subjects described
here, is presented in a separate contribution/9/.
The Distribution of Astrocytes, Oligodendroglia and Myelin in Normaland Transplanted Rat Superior Colliculus: An Immunohistochemical Study
Authors: Harvey A. R. , Plant G. W. , Kent A. P.
Published: March 2007

Immunohistochemical methods have been
used to determine the distribution of macroglia
and myelin in the normal rat superior colliculus
(SC) and in grafts of fetal tectal tissue. The fetal
tissue was derived from 15 day‐old (E15) rat
embryos and was transplanted onto the
midbrain of newborn host rats of the same
(PVG/c) strain. Antibodies to glial fibrillary
acidic protein (GFAP) and carbonic anhydrase
II (CAII) were used to visualize astrocytes and
oligodendroglia respectively. Myelin was
lmmunostained with antibodies to either
proteolipid protein (PLP) or myelin basic
protein (MBP). In the normal SC, GFAP
positive astrocytes were found scattered
throughout the SC, particularly in the
superficidi layers. They were especially
prominent at the pial surface, around major
blood vessels and at the midline between the two
colliculi. CAII immunoreactive oligodendroglia
and associated myelin were also found
throughout the SC; by far the lowest density was
seen in the stratum griseum superficiale (SGS).
Both types of macroglial cell were found in
abundance in tectal transplants, indicating that
the precursors of these glial types were present
in the E15 rat mesencephalon. In mature grafts,
large numbers of fibrous astrocytes were found
throughout the neuropil and the level of GFAP
immunoreactivity was consistently greater than in host SC. Astrocytes seemed to be maintained
in a reactive, perhaps immature state within the
grafted tissue. Tectal transplants possessed large
numbers of fully differentiated CAII‐positive
oligodendroglia and the grafts contained a dense
network of myelinated axons. However the
distribution of CAII and PLP immunoreactivity
was not homogeneous; there were localized,
well‐defined regions that contained few
oligodendroglia and relatively little myelin.
These areas stained intensely for acetylcholinesterase
(AChE) and were almost certainly
homologous to the SGS of normal SC. The
relative lack of oligodendroglia in the AChE
stained patches in grafts and in SGS in situ suggests that local factors influencing the
proliferation and distribution of oligodendroglia
in normal SC may have been operating in a
similar manner within the tectal transplant
neuropil.
Restricted Migration of Transplanted Oligodendrocytes or theirProgenitors, Revealed by Transgenic Marker MβP
Authors: Friedrich, Victor L. , Lazzarini Robert A.
Published: March 2007

Transgenic mice of line MβP3 express
bacterial β‐galactosidase in oligodendrocytes but
not other cells of the CNS. The marker enzyme,
demonstrated histochemically or by immunostaining
in oligodendrocyte cell bodies and along
myelin internodes, appears at the time of
myelination and persists thereafter; in
transplantation experiments, the marker may
serve to indicate both the source of particular
cells and their state of differentiation. The
subventricular zone of the lateral ventricle,
grafted from transgenic to wild‐type perinatal
recipient mice, yields histochemically labeled
oligodendrocytes in surrounding host tissue.
When grafts are placed in cerebral cortex near
callosal radiations, graft‐derived oligodendrocytes
are found in cerebral cortex and
subcortical white matter as far as 1.5 mm from
the site of implant but not in nearby
caudoputamen. This study is the first to
document differentiation of transplant‐derived
oligodendrocytes in normal developing CNS.
Our results are consistent with the well‐
established notion that oligodendrocyte
progenitors migrate during normal development
and suggest that such migration might be guided
or restricted by mechanisms yet to be identified.
Reconstruction of GABAergic Transmission and Behavior byStriatal Cell Grafts in Rats with Ischemic Infarcts in the Middle Cerebral Artery
Authors: Nishino Hitoo , Aihara Noritaka , Czurko András , Hashitani Takeshi , Isobe Yoshiaki , Ichikawa Osamu , Watari Hiroshi
Published: March 2007

Fetal striatal cell suspensions were grafted
stereotaxically into the infarcted striatum of
rats, and reconstruction of striatopallidal GABA
transmission and behavior were investigated.
Occlusion of the middle cerebral artery (MCA)
for one hour induced ischemic infarcts mainly in
the lateral striatum, as detected by magnetic
resonance imaging (MRI) and histology.
Ischemic rats had deficits in the performance of
a passive avoidance task, both acquisition and
retention, but no changes in general circadian
actograms. In these animals pallidal GABA,
detected by microdialysis, decreased to about
half of control levels. There were suggestions of
an improvement in passive avoidance
performance in the grafted animals. Pallidal
GABA concentrations recovered almost to
control levels, and were increased by infusions
of the GABA uptake blocker nipecotic acid.
These data indicate that neural transplantation
is a promising approach to improve the deficits
in chemical transmission and behavior following
ischemic infarcts in rat striatum.
Nerve Growth Factor with Insular Cortical Grafts Induces Recoveryof Learning and Reestablishes Graft Choline Acetyltransferase Activity
Authors: Escobar M. L. , Jiménez N. , López-García J. C. , Tapia R. , Bermúdez-Rattoni F.
Published: March 2007

Rats showing disrupted taste aversion due to
insular cortex (IC)‐lesions received either IC‐grafts
with NGF, grafts without NGF, or NGF
alone. An additional group served as lesioned
controls. Only those animals that received IC‐grafts
with NGF recovered the ability to learn
the conditioned taste aversion task, at 15 days
post‐graft. Choline acetyltransferase (ChAT)
activity in the IC‐grafts with, but not without
NGF, was similar to the IC activity of
unoperated controls. In contrast, glutamate
decarboxylase activity was similar in all the
groups. These findings suggest that IC‐grafts
associated with NGF induce recovery of
learning abilities in IC‐lesioned rats, which
correlates with reestablishment of ChAT
activity in the grafts at 15 days post‐implantation.
Basic and Clinical Studies of Pharmacologic Effects on Recoveryfrom Brain Injury
Authors: Goldstein Larry B.
Published: March 2007

Investigations in laboratory animals indicate
that certain drugs that influence specific neurotransmitters
can have profound effects on the
recovery process. Even small doses of some
drugs given after brain injury facilitate recovery
while others are harmful. Preliminary clinical
studies suggest that the same drugs that enhance
recovery in laboratory animals (e.g.,
amphetamine) may have similar effects in
humans after stroke. In addition, some of the
drugs that impair recovery of function after
focal brain injury in laboratory animals (e.g.
haloperidol, benzodiazepines, clonidine,
prazosin, phenytoin) are commonly given to
stroke patients for coincident medical problems
and may interfere with functional recovery in
humans. Until the impact of pharmacologic
agents on the recovering brain is better
understood, the available data suggest that care
should be exercised in the selection of drugs used
in the treatment of the recovering stroke patient.
Pharmacologic enhancement of recovery after
focal brain injury may be possible in humans.
Neurotransmitter Receptors in Fetal Tissue Transplants:Expression and Functional Significance
Authors: Lu Sunny Y. , Norman Andrew B.
Published: March 2007

Numerous studies have examined receptor
expression in neural transplants and their
possible role in transplant‐induced functional
recovery from lesion‐induced deficits. Herein we
attempt to summarize the results of these
studies, especially those from studies involving
striatal transplants. Autoradiographic studies
indicate that dopamine D1
and D2, muscarinic,
cholinergic, 5‐HT2, opiate μ, β
adrenergic and
cholecystokinin (CCK) receptors are present in
striatal transplants. Many of these receptors are
present regardless of the transplant location and
surrounding environment. This suggests that the
expression of these receptors is determined by
intrinsic properties of transplanted tissue, and is
independent of transplant location and
environment. Some transplant receptors, such as
dopamine D1 and D2 and muscarinic receptors
in striatal transplants, or 5‐HT2 receptors in
cortical transplants, display a patchy
distribution which is dissimilar to that in the
corresponding adult host tissue. This
manuscript discusses this “abnormal” receptor
distribution and possible explanations. Electrophysiological
studies have indicated that some of
the transplant receptors respond to physiological
and pharmacological stimulation, suggesting
that they are functional. However, the
association of receptor expression with
behavioral recovery is uncertain. The expression
of neurotransmitter receptors in neural
transplants may not be essential for the functional recovery associated with trophic
mechanisms. However, neurotrammitter
receptors may play an important role when
functional recovery requires neur0anatomical
integration between the host brain and the
transplanted tissue.
Conceptual and Practical Issues in the PharmacologicalTreatment of Brain Injury
Authors: Stein Donald G. , Glasier Marylou M. , Hoffman Stuart W.
Published: March 2007

It is only within the last ten years that
research on treatment for central nervous
system (CNS) recovery after injury has become
more focused on the complexities involved in
promoting recovery from brain injury when the
CNS is viewed as an integrated and dynamic
system. There have been major advances in
research in recovery over the last decade,
including new information on the mechanics
and genetics of metabolism and chemical
activity, the definition of excitotoxic effects and
the discovery that the brain itself secretes
complex proteins, peptides and hormones which
are capable of directly stimulating the repair of
damaged neurons or blocking some of the
degenerative processes caused by the injury
cascade. Many of these agents, plus other nontoxic
naturally occurring substances, are being
tested as treatment for brain injury. Further
work is needed to determine appropriate
combinations of treatments and optimum times
of administration with respect to the time course
of the CNS disorder. In order to understand the
mechanisms that mediate traumatic brain injury
and repair, there must be a merging of findings
from neurochemical studies with data from
intensive behavioral testing.
Factors Determining the Restoration of Circadian Behavior byHypothalamic Transplants
Authors: Vogelbaum Michael A. , Galef Jennifer , Menaker Michael
Published: March 2007

The expression of locomotor activity by
golden hamsters is temporally controlled by
circadian oscillators contained within the
suprachiasmatic nucleus (SCN). A genetic
mutation has been found that alters the
freerunning period of the locomotor activity
rhythm from the wild‐type value of ~24 hours to
~20 hours in homozygous mutants. It has been
shown previously that a transplant of fetal
hypothalamic tissue containing the SCN to a
host rendered arrhythmic by a complete lesion
of the SCN restores rhythmicity with the
freerunning period which is normally expressed
by the donor genotype. To investigate the
mechanisms by which the SCN controls the
temporal organization of behavior, we made
partial lesions to the SCN of hosts of one
genotype, and then placed hypothalamic
implants from fetal donors of a different
genotype into the lesion site. By varying the size
of the host′s partial SCN lesion and the duration
of time between lesioning and transplantation,
we have attempted to alter the relative amount
of host and donor control over the expression of
locomotor activity. We found that the expression
of donor rhythmicity requires the presence of a
lesion to the host SCN, and that the incidence of
donor expression increased as a function of host
SCN lesion size. Neither the duration of time
between lesioning and transplantation, nor the
location of the transplant within the third
ventricle had independent effects on the incidence of donor rhythm expression; however,
there was a strong suggestion of an effect of
their interaction.
Transplanted Sympathetic Neurons From Old Rats Survivein the Anterior Eye Chamber: A Histochemical and Electron Microscopic Study
Authors: Suhonen Jaana , Hervonen Antti
Published: March 2007

The purpose of this study was to investigate
the viability and ultrastructural characteristics
of intraocular superior cervical ganglion (SCG)
grafts from young (3 months), aged (24 months)
and very old (36 months) rats after short‐term
(1 month) grafting. The formaldehyde‐induced
fluorescence (FIF) technique for histochemical
demonstration of catecholamines was used to
indicate the functionality of transplanted
neurons. Ultrastructural changes in grafts were
demonstrated by electron microscopy. Four
weeks after transplantation, catecholamine
histofluorescence in young transplants was
almost as strong as in the intact ganglia, while
aged and very old grafts showed decreased
fluorescence and contained a marked
accumulation of autofluorescent lipopigment
bodies. Catecholamine histofluorescence showed
a decrease in neuronal density of 47%, 59% and
68% in young, aged and very old grafted
ganglia, respectively. The shape of most of the
transplanted neurons did not differ from that in
the intact ganglia, but the average diameter of
neurons was decreased after grafting. In
electron microscopy, both neurons with normal in vivo fine structure and neurons showing some
abnormal cytological alterations were seen in
each age group of the transplants. The most
prominent feature after grafting was the accumulation of different types of lipopigment
bodies in the perikarya of neurons. The
organization of the rough endoplasmic
reticulum was more irregular in transplanted
neurons than in intact neurons. In addition, the
amount of neurofilament aggregates increased
and some mitochondria were swollen in neurons
after transplantation. These results suggest that
young sympathetic ganglion tissue survives
rather well after transplantation into the
anterior eye chamber, while in the aged
sympathetic ganglion implants the survival rate
is poorer. However, aged and very old SCG
grafts were shown to contain and continue to
produce noradrenaline, indicating that
sympathetic neurons maintain their plasticity
and regenerative ability in advanced age.
Catecholamine histofluorescence and fine
structural changes in the cell structure of
grafted sympathetic neurons may indicate an
accelerated aging process induced by the
transplantation procedure.
Graft‐induced Recovery of Inhibitory Avoidance Conditioning in Striatal Lesioned Rats is Related to Choline Acetyltransferase Activity
Authors: Piña Ana Luisa , Ormsby Christopher Edward , Miranda María Isabel , Jiménez Nicolás , Tapia Ricardo , Bermúdez-Rattoni Federico
Published: March 2007

Four groups of male Wistar rats showing
disrupted inhibitory avoidance conditioning due
to striatal lesions received either striatal or
ventral mesencephalic brain grafts. Two
additional non‐lesioned groups were used as
controls. Half of the groups was retrained in an
inhibitory avoidance task at fifteen days
postgraft and the other half at sixty days
postgraft. Those animals receiving striatal grafts
significantly improved their ability to acquire
the inhibitory avoidance task at fifteen and sixty
days postgraft, as opposed to those receiving
mesencephalic grafts, which did not show
behavioral recovery. Choline acetyltransferase
and glutamate decarboxylase activities, as well
as dopamine content, were measured in the
grafted tissue. Striatal grafts showed levels of
choline acetyltransferase activity similar to the
control group. Moreover, a positive correlation
was found between the choline acetyltransferase
activity and the behavioral recovery. In
contrast, both glutamate decarboxylase activity
and dopamine levels were significantly lower in
striatal and in mesencephalic grafts, as
compared to the controls. These results show
that striatal but not mesencephalic grafts can
promote the restoration of the ability to acquire
an inhibitory avoidance task even at early stages
(15 days) of the development of the grafts. The
results also suggest that acetylcholine plays an
important role in behavioral recovery.
Bridging a Complete Transection Lesion of Adult Rat Spinal Cord with Growth Factor‐Treated Nitrocellulose Implants
Authors: Houle John D. , Ziegler Mei Kheng
Published: March 2007

The ability of a substrate bound
neurotrophic factor to promote growth of
ascending sensory axons across a complete
transection lesion of the rat spinal cord was
examined in a transplantation model. Aspiration
lesions created a 3 mm long cavity in the upper
lumbar spinal cord of adult rats. Five weeks
after injury two strips of nerve growth factortreated
nitrocellulose, were implanted, each in a
medio‐lateral position, and apposed to the
rostral and caudal surfaces of the cavity.
Control animals received untreated nitrocellulose
implants. Fetal spinal cord tissue was
transplanted alongsideand between these strips.
Six weeks post transplantation, animals were
sacrificed and vibratome sections through the
grafts were processed for immunocytochemical
demonstration of ingrowing axons expressing
calcitonin gene‐related peptide (CGRP‐IR),
Immunolabeled axons were abundant at the
caudal interface between host tissue and the
NGF‐treated nitrocellulose implants, with dense
fascicles of fibers abutting the grafts. As the
distance from the caudal surface increased some
CGRP‐IR fibers extended into the fetal tissue
although most appeared to remain oriented in a
longitudinal course adjacent to the nitrocellulose.
Labeled axons were evident along the
entire length of the nitrocellulose and appeared
to aggregate at the rostral tip of the implant,
with many fibers extending into the host spinal
cord rostral to the lesion/transplant site. When
untreated nitrocellulose was implanted, fewer
labeled axons appeared to extend beyond the
caudal host‐graft interface. Most CGRP‐IR
axons displayed limited association or contact
with the untreated nitrocellulose in this
condition. Computer‐assisted quantitative
analysis indicated that NGF‐treated nitrocellulose
supported regrowing host axons for
nearly three times the length exhibited by axons
associated with non‐treated nitrocellulose
implants. These results indicate that substrate
bound nerve growth factor has the capacity to
enhance the regrowth of ascending sensory
axons across a traumatic spinal cord injury site.
The potential to reestablish functional contacts
across such a lesion may be heightened by the
ability of neurotrophic factors to promote more
extensive axonal regrowth.
Retinal Afferent Ingrowth to Neocortical Transplants in the Adult Rat Superior Colliculus is due to the Regeneration of Damaged Axons
Authors: Ross D. T. , Das G. D.
Published: March 2007

Retinal afferent ingrowth to embryonic
neural transplants in the adult rat superior
colliculus may represent either sprouting of
intact axons or the regeneration of transected
axons. If ingrowth represents regeneration of
damaged retinofugai axons, then lesions that
axotomize more retinofugal axons at the
transplantation site should induce greater
retinal afferent ingrowth. Alternately, if
ingrowth represents terminal or collateral
sprouting of intact retinofugal axons at or near
the transplant/host optic layer interface, then
the magnitude of retinal afferent ingrowth
should be directly related to the total area of this
interface. To test between these two hypotheses
surgical knife wounds were made either parallel
(in the sagittal plane) or perpendicular (in the
transverse plane) to the course of axons in the
stratum opticum, embryonic neocortical tissue
was transplanted at the coordinates of these
tectal slits, and retinal afferent ingrowth
visualized 1‐90 days after surgery using
anterogradely transported HRP.

A zone of traumatic reaction (ztr) in the optic
layers was seen in every case, characterized by
hypertrophied axons and swollen terminal clubs
at 1 day. Between 30 and 90 days the damaged
retinofugal axons in the zone formed dense
fascicles and neuroma‐like tangles. Retinal
afferent ingrowth occurred only across
transplant interface regions with the ztr. The
magnitude of ingrowth was directly related to
the area of the ztr interface and not the total
optic layer interface area. Retinal afferent
ingrowth appears to reflect the intrinsic
regenerative capacity of adult mammalian
retinal ganglion cells and not sprouting of
undamaged axons.
Function and Structure in Retinal Transplants
Authors: Adolph Alan R. , Zucker Charles L. , Ehinger Berndt , Bergström Anders
Published: March 2007

Embryonic mammalian donor retina
transplanted into the subretinal space of a
mature host develops into a graft with wellorganized,
but atypical retinal structure. We
tested the effect of this organization on rabbitto‐rabbit
graft functional properties, isolating
the graft to avoid contamination of graft
responses by host retinal activity. Transient ON
or ON‐OFF spike‐like responses and local
electroretinograms (L‐ERGs) were recorded
simultaneously via a single electrode on the graft
surface. These response components depended
on stimulus diameter, sometimes in a way indicating
antagonistic center‐surround receptive
field organization and spatial tuning (43%).
Other times, the responses were an increasing
function of stimulus diameter which saturated
for large spots (57%). Response amplitudes were
transplantation surgery is to be done with
therapeutic aims.
Intracortical Dentate Fascia Grafts: Mossy Fiber Synapses in the Host Neocortex
Authors: Zhuravleva Z. N. , Vinogradova O. S.
Published: March 2007

Embryonic dentate fascia was grafted into a
cavity in the area of the adult rat neocortex
which represents the vibrissae (barrel field). We
wished to test the possibility of development of
connections between the two brain areas which
do not have synaptic or tissue contacts in situ
The unique characteristics of the giant synaptic
boutons of the dentate mossy fibers were used
for detection of the dentate synaptic contacts
with neocortical neurons at the electron
microscopic level. Ultrastructural analysis nine
months postgrafting has shown that the bundles
of mossy axons eter the host neocortex and
develop multiple terminal and en passant
contacts with typical characteristics. Neuronal
perikarya, large dendritic trunks and fine
caliber terminal dendritic branches were used
by the mossy fibers as postsynaptic targets, as
well as spines of various complexity and
configurations. The subsynaptic dendrites
seemed to be modified by synapsing giant
boutons. Accumulation of cytoplasmic organelles
was observed at these sites. Various bumps and
protuberances were formed by the subsynaptic
dendrite surface. The contents of these
appendages were variable; some of them
contained organeiles typical of dendroplasm,
while others were more spine‐like, often with
inclusion of ribosomes. It is concluded that
mossy fibers growing into the host neocortex can
develop typical contacts with inappropriate
targets with all the ultrastructural features of
functional synapses.
Behavioural Consequences of Frontal Cortex Grafts and Enriched Environments after Sensorimotor Cortex Lesions
Authors: Christie Michael A. , Dalrymple-Alford John C.
Published: March 2007

Past studies have experienced difficulty in
achieving graft survival and behavioural
recovery after sensorimotor cortex lesions. In the
present work, adult female rats trained
preoperatively to cross a narrow beam for food
reward were maintained in standard group
cages or an enriched environment, commencing
one week after a unilateral lesion. One month
post‐lesion, half of these rats received multiple
suspension grafts of (E20) fetal frontal cortex,
placed adjacent to the lesion cavity, and 8 days
later recovery of beam‐walking skills was
examined for a six‐week period. The grafts
survived in all cases with an appropriate lesion,
a notable result given the one month lesion‐graft
delay, but graft volume was not influenced by
postoperative environment. The substantial
lesion‐induced deficits evident just prior to
differential housing showed a marked reduction
by the start of post‐graft testing, but relative to
intact controls a persistent deficit in foot slip
errors occurred in all lesion groups. Irrespective
of graft status, postoperative enrichment
prevented the occurrence of severe foot slips,
especially early in retraining. The frontal grafts,
however, enhanced beam‐walking recovery by
reducing the overall frequency of foot slips on
early post‐grafting sessions, an effect we suggest
is related to graft‐derived trophic influences, but
this measure was not significantly improved by
postoperative enrichment.
Fibrin Glue Used as an Adhesive Agent in CNS Tissues
Authors: Cheng Henrich , Almström Susanne , Olson Lars
Published: March 2007

One of the limitations of many bridging
experiments in neural transplantation is that the
CNS tissues cannot be sutured. Fibrin glue is a
two‐component system derived from whole
blood which, when mixed, reproduces the final
stage of blood coagulation and solidifies. Many
experimental studies of humans and animals
show that fibrin glue repair of peripheral nerves
is almost equivalent to microsurgical sutures. In
this study, we attempted to extend its use to
CNS tissues and transplants. Two techniques
were tried: (1) Bilateral parietal knife cuts were
performed by stereotaxic technique in six rats.
Fibrin glue was applied in the right‐side cortical
lesion. Immunohistochemistry using antisera to
tyrosine hydroxylase (TH), glial fibrillary acidic
protein (GFAP), laminin and neurofilament
(NF) was essentially similar between the control
and treatment groups. The immunoreactivity of
each marker revealed no significant differences
between the two groups on days 1, 7 and 30.
There was no difference in terms of gliosis or
microvascular proliferation. (2) Embryonic day
16 fetal locus coeruleus was grafted together
with E16 cortex to the anterior chamber of sympathectomized
eyes. In the six eyes of the glue
treatment group, the parietal cortical piece and
the locus coeruleus piece were joined together
before grafting by immersing them in the
solution of fibrin glue. In the eight eyes of the
control group, pieces of parietal cortex and locus
coeruleus were introduced individually and approximated
by gently pressing the cornea. The
sizes of double grafts showed no significant
difference between groups during six weeks
postgrafting. The immunohistochemical pictures
using antisera against TH, GFAP and laminin
were similar in both groups. Catecholaminergic
fibers from the grafted locus coeruleus were
found bridging over into the parietal cortical
piece in both the control and treatment groups.
There was no significant difference in TH‐positive
nerve fiber density between tissue glue joined
and control double intraocular grafts. In
conclusion, fibrin glue can be used as an adhesive
agent in CNS tissues without hampering
the outgrowth of neurites or causing adverse
tissue reactions in fetal or adult nervous tissues.
Intracerebral Implantation of Hydrogel‐Coupled Adhesion Peptides: Tissue Reaction
Authors: Woerly S. , Laroche G. , Marchand R. , Pato J. , Subr V. , Ulbrich K.
Published: March 2007

Arg‐Gly‐Asp peptides (RGD) were synthesized
and chemically coupled to the bulk of N‐(2‐hydroxypropyl) methacrylamide‐based polymer
hydrogels. Fourier Transform Infrared Spectroscopy
(FFIR) and amino acid analysis confirmed
the peptide coupling to the polymer. Activated
and control (unmodified) polymer matrices were
stereotaxically implanted in the striata of rat
brains, and two months later the brains were
processed for immunohistochemistry using antibodies
for glial acidic fibrillary protein (GFAP),
laminin and neurofilaments. RGD‐containing
polymer matrices promoted stronger adhesion to
the host tissue than the unmodified polymer
matrices. In addition, the RGD‐grafted polymer
implants promoted and supported the growth
and spread of GFAP‐positive glial tissue onto
and into the hydrogels. Neurofilament‐positive
fibers were also seen running along the surface
of the polymer and, in some instances, penetrating
the matrix. These findings are discussed
in the context of using bioactive polymers as a
new approach for promoting tissue repair and
axonal regeneration of damaged structures of
the central nervous system.
Expression of Nerve Growth Factor, Brain‐Derived Neurotrophic Factor and Neurotrophin‐3 mRNAs in Human Cortical Xenografts
Authors: Humpel Christian , Strömberg Ingrid , Olson Lars
Published: March 2007

Trophic factors play an important role in the
development of neurons and glia. In order to
study the involvement of neurotrophins in
human cortical development, human fetal
parietal cortical tissue, obtained after early
elective abortions, was transplanted to cortical
cavities in immunosuppressed rats. Using in situ
hybridization it was demonstrated that nerve
growth factor, brain‐derived neurotrophic factor
and neurotrophin‐3 mRNAs are expressed in
developing human cortical xenografts. We conclude
that neurotrophins may play a role in
human cortical development and rat‐derived
astroglial cells could be involved in establishing
reciprocal “permissive sites”.
Optimization of Adrenal Medullary Allograft Conditions for Pain Alleviation
Authors: Wang Hong , Sagen Jacqueline
Published: March 2007

Previous findings in our laboratory have
demonstrated that transplants of adrenal
medullary tissue into the spinal subarachnoid
space can alleviate pain, most likely via
sustained local release of pain‐reducing
neuroactive substances from the transplanted
chromaffin cells. The success of this work in
animal models has led to preliminary clinical
trials with promising results. However, before
large‐scale clinical studies are undertaken,
numerous issues should be resolved, many of
which can be readily addressed initially in the
laboratory. One of these is the amount of donor
adrenal medullary tissue necessary to produce
long‐term antinociception. Although tissue from
two adrenal glands has generally been used, it is
unknown whether less would be equally
effective, or more could increase analgesic
potency. To address this, various amounts of
adrenal medullary tissue, ranging from one to
ten donor glands, were used. Results showed
lowered antinociceptive benefits when only one
adrenal medulla was used, but only small and
short‐lived increases when donor material was
increased substantially. In addition, assays of
atecholamine and Met‐enkephalin release in
the host spinal CSF revealed only slight further
increases following the transplantation of more
than 2‐4 glands. These results indicate that a
small amount of adrenal medullary tissue is
necessary and sufficient to produce sustained
antinociception, and suggest that higher
amounts may result in tolerance development or
feedback inhibition. Another important issue is
the ability to retain antinociceptive potency if
donor tissue is maintained in culture prior to
transplantation, since the coordination of donor
harvesting and recipient availability is often
difficult. To address this, donor adrenal
medullary tissue was maintained in explant
culture for various periods following dissection.
Results indicated that adrenal medullary tissue
can be maintained in culture for up to 30 days
prior to transplantation without decrement in
antinociceptive potency, and that a period of 7‐21
days results in improved graft viability.
Results of this study indicate that some of the
critical issues for successful neural transplantation
outcomes can be initially addressed in
pre‐clinical studies.
Morphogenetic Plasticity of Neuronal Elements in Cerebellar Glomeruli during Deafferentation‐Induced Synaptic Reorganization
Authors: Hámori József , Jakab Robert L. , Takács József
Published: March 2007

Reorganization of the cerebellar glomerulus, the main synaptic complex within the granule cell layer, was investigated using quantitative morphological techniques. All afferents to the cerebellar cortex, including mossy‐fibers, were surgically destroyed by undercutting the cerebellar vermis. Fifteen days after the operation, which resulted in the removal of the main excitatory afferent to the glomerulus, a significant reorganization of the whole synaptic complex was observed, whereas the structural integrity of the glomerulus was remarkably well preserved. This was indicated by the observation that the number of granule cell dendrites (≈50 per glomerulus), as well as the number of dendritic digits (≈210 per glomerulus) bearing most of the ≈230 synaptic junctions per glomerulus, did not change significantly after mossy‐fiber degeneration. The total number of synapses in the reorganized glomerulus did not change either, despite the disappearance of two‐thirds of (excitatory) synaptic junctions caused by mossy‐fiber degeneration. In the reorganized glomeruli, however, the inhibitory, GABA‐containing Golgi axonal varicosities became the dominant synaptic type—about four‐fifths (≈200) of all synapses within the glomerulus—whereas the dendritic synapses between the granule cells represented only one‐fifth of all synaptic junctions. The quantitative data of the reorganized cerebellar glomerulus demonstrate both a remarkable constancy and a plasticity of he excitatory granule cells and inhibitory Golgi neurons building up this synaptic complex. constancy (the preservation of certain specific structural features) is represented by an eventually unchanged number of dendrites and synaptic junctions within the deafferented lomerulus. Such constancy was made possible, however, by the morphogenetic plasticity of both nerve‐cell types to produce new, dendrodendritic and axo‐dendritic synapses to compensate for the loss of mossy‐fiber synapses.
A Rapid Replacement of Vimentin‐Containing Radial Glia by Glial Fibrillary Acidic Protein‐Containing Astrocytes in Transplanted Telencephalon
Authors: Tuba Andrea , Kállai Lázló , Kálmán Mihály
Published: March 2007

The present study follows the early events in the development of astroglia in rat embryonic (El5) tissue grafted into the cortex of adult rats. Astroglial elements (radial glia and astrocytes) were studied by glial fibrillary acidic protein (GFAP) and vimentin immunohistochemistry on post‐transplantation (PT) days 7, 11, 14, 17, and 21. At PT7, GFAP‐immunopositive elements
were only scarce fibers in the transplants. At PTll, a dense network of long, GFAP‐immunopositive fibers enmeshed the entire
transplant, and astrocytes were already recognized. The fibers also showed vimentin immunoreactivity. By PT14, astrocytes became the predominant GFAP‐labeled elements, although a few long fibers persisted. When compared with in situ development, the grafts
showed earlier GFAP‐immunoreactivity and earlier appearance of astrocytes, as well as a more rapid transition from the immature to the
mature form of the glial system.
Septal Fetal Tissue Transplants Restore Long‐Term Potentiation in the Dentate Gyrus of Fimbria‐Formix‐Lesioned Rats
Authors: Bergado Jorge A. , Moreno Heriberto , Soto Johanka , Castellano Orlando , Castillo Lázara
Published: March 2007

Two groups of Sprague‐Dawley male rats received bilateral aspirative lesions of the fimbria fornix under chloral hydrate anesthesia.
One group (n = 9)
received no further treatment (lesioned). In the second group (n = 8)
, a piece of septal fetal tissue, obtained at day E15‐16, was implanted into each lesion cavity (transplanted). A third group consisted of shamlesioned rats (controls, n = 14
). Two months after the operations, a recording electrode was implanted in the hilar region of the dentate gyrus of each animal, and a bipolar stimulating electrode was implanted in the perforant path. Long‐term potentiation at 400 Hz was induced and followed for two hours. FF‐lesioned rats showed an impaired potentiation of the field excitatory post‐synaptic potential, which rapidly declined to basal levels within 15 minutes. The transplanted rats showed a normal potentiation of this parameter, similar to that seen in the. control animals. A decrease in choline acetyltransferase activity in the hippocampi of the lesioned animals showed a tendency toward recovery after septal fetal tissue transplantation. In all the dorsal hippocampal areas of the lesioned animals, acetylcholinesterase histochemistry showed an almost complete loss of enzymatic activity, which was partially restored by the transplants. The improved synaptic plasticity in the transplanted animals might be related to septal transplant‐induced recovery of mnemonic functions.
Changes in L1 Antigen Expression in the Rat Striatum After Substantia Nigra Lesions
Authors: Poltorak Maciej , Williams Jamesine R. , Moore Kraig D. , Freed Willam J.
Published: March 2007

L1 antigen promotes neurite outgrowth from dopaminergic neurons in tissue culture. In the present study, we examined the effects of dopaminergic deafferentation of the striatum on L1 expression. In the medial‐periventricular part of the striatum, both complete and partial
substantia nigra (SN) lesions decreased L1 expression. Complete lesions increased L1 expression in the dorso‐medial and ventrolateral
parts of the striatum on the lesioned side when compared with that on the non‐lesioned side. The decrease in the ventro‐lateral area was
maintained in animals examined three months after the lesioning. Animals with partial SN lesions showed a different pattern of altered L1
expression. After frontal cortex lesions, changes in L1 expression also occur preferentially in the dorso‐medial and periventricular striatum. Therefore, the results indicate a complex regulation of L1 expression after damage of striatal circuitry, manifested by a preferential
occurrence of changes in periventricular regions.