Search PubMed⌕ Search

Biomedical subjects

A Reiner

Publications and source records attributed to A Reiner.

At least 127 records · Page 7Linked to original sources

Prognostic impact of DNA content and AUER classification in primary fallopian tube carcinoma.

DNA ploidy has been studied in 61 primary fallopian tube carcinomas using image-cytometry. The investigation also included survival analysis, and ploidy classification according to AUER was performed in order to evaluate its prognostic impact for fallopian tube carcinoma. A high number of aneuploid cases were observed (79% aneuploid vs. 21% euploid tumors). The high incidence of aneuploid tumors was consistently observed among all FIGO-stages as well as all groups of histologic grading. There was no correlation between ploidy and FIGO-stage or histologic grading. Patients with euploid DNA content showed a median survival of 34 months compared to 24 months for aneuploid cases (log-rank, P = 0.83). No correlation between the AUER classification and FIGO-stage or histologic grading could be observed. Tumors with an AUER type I and II (75th quantile 41 months) showed a better outcome than tumors with AUER III and IV (75th quantile 19 months). Although these results did not reach statistical significance (P = 0.07), a trend could be observed. Therefore AUER classification may be useful as an objective prognostic parameter. The high incidence of aneuploid tumors could be an expression of the high biologic aggressiveness of primary fallopian tube cancer which has been repeatedly mentioned in the past.

Adenocarcinoma↗

Organization of the avian "corticostriatal" projection system: a retrograde and anterograde pathway tracing study in pigeons.

Birds have well-developed basal ganglia within the telencephalon, including a striatum consisting of the medially located lobus parolfactorius (LPO) and the laterally located paleostriatum augmentatum (PA). Relatively little is known, however, about the extent and organization of the telencephalic "cortical" input to the avian basal ganglia (i.e., the avian "corticostriatal" projection system). Using retrograde and anterograde neuroanatomical pathway tracers to address this issue, we found that a large continuous expanse of the outer pallium projects to the striatum of the basal ganglia in pigeons. This expanse includes the Wulst and archistriatum as well as the entire outer rind of the pallium intervening between Wulst and archistriatum, termed by us the pallium externum (PE). In addition, the caudolateral neostriatum (NCL), pyriform cortex, and hippocampal complex also give rise to striatal projections in pigeon. A restricted number of these pallial regions (such as the "limbic" NCL, pyriform cortex, and ventral/caudal parts of the archistriatum) project to such ventral striatal structures as the olfactory tubercle (TO), nucleus accumbens (Ac), and bed nucleus of the stria terminalis (BNST). Such "limbic" pallial areas also project to medialmost LPO and lateralmost PA, while the hyperstriatum accessorium portion of the Wulst, the PE, and the dorsal parts of the archistriatum were found to project primarily to the remainder of LPO (the lateral two-thirds) and PA (the medial four-fifths). The available evidence indicates that the diverse pallial regions projecting to the striatum in birds, as in mammals, are parts of higher order sensory or motor systems. The extensive corticostriatal system in both birds and mammals appears to include two types of pallial neurons: 1) those that project to both striatum and brainstem (i.e., those in the Wulst and the archistriatum) and 2) those that project to striatum but not to brainstem (i.e., those in the PE). The lack of extensive corticostriatal projections from either type of neuron in anamniotes suggests that the anamniote-amniote evolutionary transition was marked by the emergence of the corticostriatal projection system as a prominent source of sensory and motor information for the striatum, possibly facilitating the role of the basal ganglia in movement control.

Animals↗

Pulse cyclophosphamide therapy for refractory autoimmune thrombocytopenic purpura.

Autoimmune thrombocytopenic purpura (AITP) is generally a chronic disorder in affected adults. Twenty-five percent of these patients will become refractory to routine therapy (corticosteroids and splenectomy), as well as most other available agents. Intravenous pulse cyclophosphamide therapy was used to treat 20 patients with severe refractory AITP who had previously failed to achieve a sustained remission with a mean of 4.8 agents (range 2 to 8). Patients received 1 to 4 doses (mean 2.0) of 1.0 to 1.5 g/m2 intravenous cyclophosphamide per course. Of the 20 patients treated with pulse cyclophosphamide therapy, 13 patients (65%) achieved a complete response (CR), four (20%) a partial response (PR), and three patients (15%) failed to respond. Of the 13 complete responders, eight have remained in remission with stable platelet counts during followup intervals of 7 months to 7 years (median 2.5 years). Five patients developed recurrent AITP 4 months to 3 years following a CR. Of these, two patients responded to subsequent courses of pulse cyclophosphamide therapy with current remissions of 1 and 4 years. Of the four patients who obtained a PR, two remain in partial remission after 10 months and 4 years; one relapsed after 18 months and, after retreatment, is still in remission at 6 months. Of the patient characteristics examined, duration of disease was most strongly associated with response to pulse cyclophosphamide. Side-effects of treatment included neutropenia (three patients, one of whom developed staphylococcal sepsis), acute deep venous thrombosis (two patients), and psoas abscess (one patient). Intravenous pulse cyclophosphamide should be strongly considered in the treatment of patients with refractory AITP. There is a relatively low incidence of side-effects, and it can be administered easily on an out-patient basis.

Adolescent↗

Glutamate-mediated excitotoxic death of cultured striatal neurons is mediated by non-NMDA receptors.

Considerable interest has focused on the role of glutamate-mediated excitotoxicity in neurodegenerative disorders of the basal ganglia. The in vitro data on the receptor mechanisms involved in this process, however, have been inconclusive. Some studies have indicated that excitotoxins acting at NMDA receptors kill striatal neurons and others have indicated that NMDA receptor-mediated excitotoxic death of striatal neurons is minimal in the absence of cortex. In the present study, we used a pharmacological approach to carefully reexamine this issue in 2-week-old cultures of striatal neurons dissociated from E17 rat embryos. The sensitivity of these neurons to glutamate agonists and antagonists was determined by monitoring cell loss in identified regions of the growth dishes. We found that glutamate killed striatal neurons with an EC50 of 100 microM. This loss was not mediated by NMDA receptors, since it was not reduced by the NMDA receptor antagonist APV (0.1-1.0 mM). Consistent with this result, up to 50 mM NMDA receptor-specific excitotoxin quinolinic acid (QA) did not affect neuronal survival. Depolarizing the QA-exposed neurons with 35 mM potassium chloride to enhance NMDA receptor activation by QA also did not produce neuron loss. The metabotropic glutamate receptor antagonist AP3 (500 microM) also had no effect on the striatal neuron loss produced by 100 microM glutamate. In contrast, the non-NMDA antagonist GYKI 52466 (100 microM) did block the excitotoxic effect of glutamate (100 microM). Specific AMPA and KA receptor agonists and the non-NMDA antagonist GYKI 52466 revealed that the non-NMDA receptor-mediated excitotoxic effect of glutamate was mediated by KA receptors. These results suggest that cultured striatal neurons are directly vulnerable to non-NMDA glutamate agonists, but not to NMDA and metabotropic glutamate agonists. Thus, non-NMDA receptors may play a greater role in the excitotoxic death of striatal neurons in disease and experimental animal models than previously realized.

Animals↗

Brainstem motoneuron pools that are selectively resistant in amyotrophic lateral sclerosis are preferentially enriched in parvalbumin: evidence from monkey brainstem for a calcium-mediated mechanism in sporadic ALS.

Some brainstem motoneuron groups appear more resistant to the process of neurodegeneration in ALS (for example, oculomotor, trochlear, and abducens nuclei) than others (for example, trigeminal, facial, ambiguus, and hypoglossal nuclei). The possibility that the differential presence of the calcium-chelating protein parvalbumin might underlie this difference in vulnerability was examined immunohistochemically as a way to determine whether a calcium-mediated mechanism might be involved in ALS. In normal monkey brainstem, we found that the abundance of parvalbumin-containing neurons in the oculomotor, trochlear, and abducens nuclei was approximately 90% of the abundance of choline acetyltransferase (CHAT)-containing motoneurons. In contrast, the abundance of parvalbumin-containing neurons in the other brainstem motor nuclei innervating skeletal muscle (trigeminal, facial, ambiguus, and hypoglossal) was only about 30-60% of the abundance of CHAT-containing motoneurons. Since some of these motoneuron pools contain nonmotoneuron internuclear neurons that might be parvalbumin-containing, we also carried out double-label studies to specifically determine the percentage of cholinergic motoneurons that contained parvalbumin in each of these motoneuron pools. We found that 85-100% of the oculomotor, trochlear, and abducens motoneurons were parvalbumin-containing. In contrast, only 20-30% of the trigeminal, facial, ambiguus, and hypoglossal motoneurons were parvalbumin-containing. These results raise the possibility that motoneuron death in sporadic ALS is related to some defect that promotes cytosolic calcium accumulation in motoneurons. This excess calcium entry may promote cell death via an excitotoxic pathway. Motoneurons rich in parvalbumin may resist the deleterious effects of this putative calcium gating defect because they are better able to sequester the excess calcium.

Amyotrophic Lateral Sclerosis↗

The relationship of choroidal blood flow and accommodation to the control of ocular growth.

We have carried out a number of different studies in chicks to examine the relationship between choroidal blood flow and myopic eye growth, and between accommodation and myopic eye growth. Our studies on choroidal blood flow show that myopic eye growth produced by form vision degradation leads to dramatic reductions in choroidal blood flow. These reductions appear directly attributable to the eye enlargement and the reduction in choroidal blood flow does not appear to be permissive for eye growth, since experimentally reduced choroidal blood flow hinders eye growth. Choroidal blood flow that is slightly above normal, however, may slightly enhance eye growth. Our studies on accommodation do not reveal any major necessary role of accommodation in regulating normal growth or in form vision degradation induced myopic eye growth. We found preliminary evidence, however, that chronically stimulating accommodation over a 2 week period, thereby producing excessive time in accommodation, may be sufficient for yielding a small but significant degree of myopic refractive error. Our studies suggest that neither fluctuations in choroidal blood flow nor an intact accommodative apparatus are essential for normal eye growth or myopic eye growth produced by form deprivation. Further studies are needed to confirm that excessive time in accommodation might be sufficient for producing myopia. Finally, our finding that choroidal blood flow is substantially reduced in myopic eyes may have implications for the etiology of the retinal problems suffered by humans with moderate to severe myopia.

Accommodation, Ocular↗

Thalamostriatal projection neurons in birds utilize LANT6 and neurotensin: a light and electron microscopic double-labeling study.

Based on its location, connectivity and neurotransmitter content, the dorsal thalamic zone in birds appears to be homologous to the intralaminar, midline, and mediodorsal nuclear complex in the thalamus of mammals. We investigated the neuroactive substances used by thalamostriatal projection neurons of the dorsal thalamic zone in the pigeon. Single-labeling experiments showed that many neurons in the dorsal thalamic zone are immunoreactive for neurotensin and the neurotensin-related hexapeptide, (Lys8,Asn9)NT(8-13) (LANT6). Double-labeling experiments, using the retrograde fluorescent tracer, FluoroGold, combined with fluorescence immunocytochemistry for either LANT6 or neurotensin, showed that neurotensin- and LANT6-containing neurons in the dorsal thalamic zone project to the striatum of the basal ganglia. Immunofluorescence double-labeling experiments showed that neurotensin and LANT6 are often (possibly always) co-expressed in neurons in the dorsal thalamic zone. Electron microscopic immunohistochemical double-labeling showed that LANT6 terminals in the striatum make asymmetric contacts with heads of spines labeled for substance P and heads of spines not labeled for substance P, suggesting that these terminals synapse with both substance P-containing and non-substance P-containing medium spiny striatal projection neurons. These findings indicate that LANT6 and neurotensin may be utilized as neurotransmitters in thalamostriatal projections in birds and raise the possibility that this may also be the case in other amniotes.

Animals↗

Interphase cytogenetics reveals a high incidence of aneuploidy and intra-tumour heterogeneity in breast cancer.

The occurrence of aberrations involving chromosomes 11 and 17 in malignant tissues of breast cancer patients has not yet been studied systematically. Using fluorescence in situ hybridisation (FISH) with centromere-specific probes, we determined chromosome 11 and 17 status in interphase nuclei from primary and/or metastatic breast cancer cells. In all cancerous specimens obtained from 30 patients, FISH identified cells with clonal chromosomal abnormalities, with aneuploidy rates ranging from 6% to 92% (median 59%). There was a gain of centromeric signals for chromosome 11, most likely corresponding to hyperploidy; aberrations of chromosome 17 in specimens from 26 patients (87%) were hyperploid as well; however, four cases (13%) showed loss of chromosome 17 centromeres. All specimens contained heterogeneous aneuploid cell populations with excessive gain of signals in some cases. The pattern of aneuploidy did not appear to correlate with tumour grade/stage and was comparable in primary tumours and corresponding metastatic axillary lymph nodes, indicative of genetic instability early in tumour development. Screening with a panel of FISH probes may lead to enhanced sensitivity and specificity in detecting malignant cells, as demonstrated in this study with effusions which could not be conclusively interpreted as being malignant by cytological criteria.

Adult↗

Neurotransmitter organization and connectivity of the basal ganglia in vertebrates: implications for the evolution of basal ganglia.

The basal ganglia in modern mammals, birds and reptiles (i.e. modern amniotes) are very similar in connections and neurotransmitters, suggesting that the evolution of the basal ganglia in amniotes has been very conservative. For example, the basal ganglia in all amniotes possess a dorsal striatum containing two main populations of projection neurons, substance P-containing (SP+) and enkephalin-containing (ENK+) neurons, which have major projections to the dorsal pallidum and the tegmentum (ventral tegmental area and substantia nigra, or VTA/SN). The VTA/SN, in turn, has a major dopaminergic (DA+) projection to the striatum in all amniotes. In this paper, we review these data on the basal ganglia in amniotes and note points of similarity and difference in the functional circuitry of the basal ganglia among amniotes. In addition, we review recent findings on the neurotransmitter organization and connectivity of the basal ganglia in amphibians and fishes, with the goal of assessing whether a basal ganglia showing the same basic features as in amniotes is observed in anamniotes. Published data indicate that in at least two groups of fishes (cartilaginous fishes and lungfishes) and apparently in amphibians, the basal ganglia is present and consists of a distinct striatum and pallidum. The striatum of amphibians, cartilaginous fishes, and lungfishes contain SP+ and ENK+ neurons that seem to project to the pallidum as well as to a brainstem cell group that appears comparable to the VTA/SN of amniotes. Data for ray-finned fishes also suggest the presence of a striatum containing SP+ and ENK+ neurons that projects to VTA/SN-like brainstem cell group. In the basal ganglia of ray-finned fishes, however, a distinct pallidum had not been identified. Finally, the brainstem cell group receiving striatal input in all anamniotes contains DA+ neurons that seem to project to the striatum. The present analysis suggests that a rudimentary basal ganglia was already present in the brain of the ancestral jawed vertebrates. This rudimentary basal ganglia likely consisted of a striatum and a pallidum, and the striatum probably already possessed the same basic connections and some of the same basic cell types as the basal ganglia of modern jawed vertebrates.

Animals↗

Damage to type II collagen in aging and osteoarthritis starts at the articular surface, originates around chondrocytes, and extends into the cartilage with progressive degeneration.

Enhanced denaturation of type II collagen fibrils in femoral condylar cartilage in osteoarthritis (OA) has recently been quantitated immunochemically (Hollander, A.P., T.F. Heathfield, C. Webber, Y. Iwata, R. Bourne, C. Rorabeck, and A.R. Poole. 1994. J. Clin. Invest. 93:1722-1732). Using the same antibody that only reacts with denatured type II collagen, we investigated with immunoperoxidase histochemistry (results were graded for analysis) the sites of the denaturation (loss of triple helix) of this molecule in human aging (at autopsy, n= 11) and progressively degenerate (by Mankin grade [MG]) OA (at arthroplasty, n= 51) knee condylar cartilages. Up to 41 yr, most aging cartilages (3 of 4) (MG 0-4) showed very little denaturation. In most older cartilages, (4 of 7) (MG 2-4), staining was observed in the superficial and mid zones. This pattern of collagen II denaturation was also seen in all OA specimens with increased staining extending to the deep zone with increasing MG. Collagen II staining correlated directly both with MG and collagen II denaturation measured by immunoassay. Cartilage fibrillation occurred in OA cartilages with increased penetration of the staining for collagen II denaturation into the mid and deep zones and where denaturation was more pronounced by immunoassay. Thus in both aging and OA the first damage to type II collagen occurs in the superficial and upper mid zone (low MG) extending to the lower mid and deep zones with increasing degeneration (increasing MG). Initial damage is always seen around chondrocytes implicating them in the denaturation of type II collagen.

Adult↗

Relationship of intraoperative electrophysiological criteria to outcome after selective functional posterior rhizotomy.

At British Columbia's Children's Hospital, the criteria used in selective functional posterior rhizotomy (SFPR) evolved in three distinct phases. In Phase 1 the electrophysiological criteria for abnormality included a low threshold to a single stimulation, a sustained response to 50-Hz stimulation, and spread outside the segmental level being stimulated. In Phase 2 the electrophysiological criteria were unchanged, but fewer L3-4 nerve roots were cut. In Phase 3, fewer L3-4 nerve roots were cut, as in Phase 2, but based on the results of posterior nerve root stimulation in nonspastic controls, the only electrophysiological criterion used was contralateral and suprasegmental spread. The present study examined the relationship between the criteria used in each phase and patient outcome. The records of 77 consecutive children who underwent SFPR and had a minimum follow-up period of 1 year were reviewed, comprising 25, 19, and 33 patients in Phases 1, 2, and 3, respectively. Outcome parameters included quantitative assessments of lower-limb spasticity and range of motion, and qualitative assessments of lower-limb function. In Phase 3, 52% of the nerve roots were cut, compared to 66% in Phases 1 and 2. In all three phases there was a significant decrease in lower-limb spasticity and an increase in range of movement, with the smallest decrease in spasticity in Phase 3. Over 90% of children in each phase improved with respect to lower-limb function, and excluding independent walkers and quadriplegics confined to a wheelchair, improvement in the level of ambulation occurred in 87.5%, 71.4%, and 73.7% of patients, in Phases 1, 2, and 3, respectively.

Adolescent↗

DNA ploidy in primary fallopian-tube carcinoma using image cytometry.

Determination of DNA ploidy in 61 samples of primary Fallopian-tube carcinoma (FTC) by use of image cytometry is presented. Of these samples, 48 showed an aneuploid DNA content. Patients with euploid DNA content showed a median survival time of 33.8 months compared to 24.5 months for aneuploid cases. A high incidence of aneuploid tumors was consistently observed among all FIGO stages and in all groups of histologic grading. However, no correlation between ploidy and FIGO stage or histologic grading could be demonstrated. This observation could be regarded as a marker for the high aggressiveness of FTC which has been repeatedly described in the past.

Adult↗

Distributions of GABAA, GABAB, and benzodiazepine receptors in the forebrain and midbrain of pigeons.

Autoradiographic and immunohistochemical methods were used to study the distributions of GABAA, GABAB and benzodiazepine (BDZ) receptors in the pigeon fore- and midbrain. GABAA, GABAB and BDZ binding sites were found to be abundant although heterogeneously distributed in the telencephalon. The primary sensory areas of the pallium of the avian telencephalon (Wulst and dorsal ventricular ridge) tended to be low in all three binding sites, while the surrounding second order belt regions of the pallium were typically high in all three. Finally, the outermost rind of the pallium (termed the pallium externum by us), which surrounds the belt regions and projects to the striatum of the basal ganglia, was intermediate in all three GABAergic receptors types. Although both GABAA and benzodiazepine receptors were abundant within the basal ganglia, GABAA binding sites were densest in the striatum and BDZ binding sites were densest in the pallidum. Among the brainstem regions receiving GABAergic basal ganglia input, the anterior and posterior nuclei of the ansa lenticularis showed very low levels of all three receptors, while the lateral spiriform nucleus and the ventral tegmental area/substantia nigra complex contained moderate abundance of the three binding sites. The dorsalmost part of the dorsal thalamus (containing nonspecific nuclei) was rich in all three binding sites, while the more ventral part of the dorsal thalamus (containing specific sensory nuclei), the ventral thalamus and the hypothalamus were poor in all three binding sites. The pretectum was also generally poor in all three, although some nuclei displayed higher levels of one or more binding sites. The optic tectum, inferior colliculus, and central gray were rich in all three sites, while among the isthmic nuclei, the parvicellular isthmic nucleus was conspicuously rich in BDZ sites. The results show a strong correlation of the regional abundance of GABA binding sites with previously described distributions of GABAergic fibers and terminals in the avian forebrain and midbrain. The regional distribution of these binding sites is also remarkably similar to that in mammals, indicating a conservative evolution of forebrain and midbrain GABA systems among amniotes.

Animals↗

Dopaminergic terminals form synaptic contacts with enkephalinergic striatal neurons in pigeons: an electron microscopic study.

Medium spiny projection neurons of the striatum consist of two major neuropeptide-specific types, one type containing substance P and another type containing enkephalin. Both of these types have been shown to receive dopaminergic input onto their perikarya and proximal dendrites. However, whether each of these types receives direct dopaminergic input onto distal dendritic shafts and onto dendritic spines has not been explored in depth. In the present study, we used electron microscopic immunohistochemical double-label techniques to examine the synaptic organization of dopaminergic input onto enkephalin-positive (ENK+) striatal neurons in pigeons, in whom ENK+ striatal perikarya, dendritic shafts and spines can be readily labeled. Antibodies against tyrosine hydroxylase were used to label dopaminergic terminals using a silver-intensified immunogold method. ENK+ neurons were labeled using diaminobenzidine. We found that dopaminergic terminals make appositions and form symmetric synapses with the perikarya, dendritic shafts, and dendritic spine necks of ENK+ striatal neurons. Thus, nigral dopaminergic neurons provide a monosynaptic input onto ENK+ striatal neurons in a manner similar to that described previously by us for substance P-positive striatal medium spiny neurons.

Animals↗

Distribution of choline acetyltransferase immunoreactivity in the pigeon brain.

We have investigated the distribution of cholinergic perikarya and fibers in the brain of the pigeon (Columba livia). With this aim, pigeon brain sections were processed immunohistochemically by using an antiserum specific for chicken choline acetyltransferase. Our results show cholinergic neurons in the pigeon basal telencephalon, the hypothalamus, the habenula, the pretectum, the midbrain tectum, the dorsal isthmus,the isthmic tegmentum, and the cranial nerve motor nuclei. Cholinergic fibers were prominent in the dorsal telencephalon, the striatum, the thalamus, the tectum, and the interpeduncular nucleus. Comparison of our results with previous studies in birds suggests some major cholinergic pathways in the avian brain and clarifies the possible origin of the cholinergic innervation of some parts of the avian brain. In addition, comparison of our results in birds with those in other vertebrate species shows that the organization of the cholinergic systems in many regions of the avian brain (such as the basal forebrain, the epithalamus, the isthmus, and the hindbrain) is much like that in reptiles and mammals. In contrast, however, birds appear largely to lack intrinsic cholinergic neurons in the dorsal ("neocortex-like") parts of the telencephalon.

Animals↗

The distribution of GABA-containing perikarya, fibers, and terminals in the forebrain and midbrain of pigeons, with particular reference to the basal ganglia and its projection targets.

Immunohistochemical techniques were used to study the distributions of glutamic acid decarboxylase (GAD) and gamma-aminobutyric acid (GABA) in pigeon forebrain and midbrain to determine the organization of GABAergic systems in these brain areas in birds. In the basal ganglia, numerous medium-sized neurons throughout the striatum were labeled for GABA, while pallidal neurons, as well as a small population of large, aspiny striatal neurons, labeled for GAD and GABA. GAD+ and GABA+ fibers and terminals were abundant throughout the basal ganglia, and GABAergic fibers were found in all extratelencephalic targets of the basal ganglia. Most of these targets also contained numerous GABAergic neurons. In pallial regions, approximately 10-12% of the neurons were GABAergic. The outer rind of the pallium was more intensely labeled for GABAergic fibers than the core. The olfactory tubercle region, the ventral pallidum, and the hypothalamus were extremely densely labeled for GABAergic fibers, while GABAergic neurons were unevenly distributed in the hypothalamus. GABAergic neurons and fibers were abundant in the dorsalmost part of thalamus and the dorsal geniculate region, while GABAergic neurons and fibers were sparse (or lightly labeled) in the thalamic nuclei rotundus, triangularis, and ovoidalis. Further, GABAergic neurons were abundant in the superficial tectal layers, the magnocellular isthmic nucleus, the inferior colliculus, the intercollicular region, the central gray, and the reticular formation. GABAergic fibers were particularly abundant in the superficial tectal layers, the parvocellular isthmic nucleus, the inferior colliculus, the intercollicular region, the central gray, and the interpeduncular nucleus. These results suggest that GABA plays a role as a neurotransmitter in nearly all fore- and midbrain regions of birds, and in many instances the observed distributions of GABAergic neurons and fibers closely resemble the patterns seen in mammals, as well as in other vertebrates.

Animals↗

Relative survival of striatal projection neurons and interneurons after intrastriatal injection of quinolinic acid in rats.

An excitotoxic process mediated by the NMDA type glutamate receptor may be involved in striatal neuron death in Huntington's disease (HD). To explore this possibility, we have injected an NMDA-receptor-specific excitotoxin, quinolinic acid (QA), into the striatum in adult rats and 2-4 months postlesion explored the relative patterns of survival for the various different types of striatal projection neurons and interneurons and for the striatal efferent fibers in the different striatal projection areas. The perikarya of specific types of striatal neurons were identified by neurotransmitter immunohistochemical labeling or by retrograde labeling from striatal target areas, while the striatal efferent fiber plexuses were identified by neurotransmitter immunohistochemical labeling. The pattern of survival for the perikarya of each neuron type as a function of distance from the center of the injection site was determined, and the relative survival of each type was compared. For the fibers in target areas, computer-assisted image analysis was used to determine the degree of fiber loss for each projection target. In the study of perikaryal vulnerability, we found that the somatostatin-neuropeptide Y (SS/NPY) interneurons were the most vulnerable to QA and the cholinergic neurons were invulnerable to QA. The perikarya of all projection neuron types (striatopallidal, striatonigral, and striato-entopeduncular) were less vulnerable than the SS/NPY interneurons and more vulnerable than the cholinergic interneurons. Among projection neuron perikarya, there was evidence of differential vulnerability, with striatonigral neurons appearing to be the most vulnerable. Examination of immunolabeled striatal fibers in the striatal target areas indicated that striato-entopeduncular fibers better survived intrastriatal QA than did striatopallidal or striatonigral fibers. The apparent order of vulnerability observed in this study among projection neurons and/or their efferent fiber plexuses and the invulnerability observed in this study of cholinergic interneurons is similar to that observed in HD. The vulnerability of the SS/NPY interneurons to QA is, however, in stark contrast to their invulnerability in HD. The results thus suggest that although the excitotoxin hypothesis of striatal neuron death in HD has merit, QA injections into adult rat striatum do not strictly mimic the outcome in HD. This suggests that either adult rats are not a completely suitable subject for mimicking HD or the HD excitotoxic process does not involve a freely circulating excitotoxin such as QA.

Animals↗