Brain serotonin transporter binding in non-depressed patients with Parkinson's disease.

Early post-mortem data suggest that damage to brain serotonin neurones might play a role in some features (e.g., depression) of Parkinson's disease (PD). However, it is not known whether such damage is a typical characteristic of living patients with PD or whether the changes are regionally widespread. To address this question we measured, by positron emission tomography imaging, levels of the brain serotonin transporter (SERT), a marker for serotonin neurones, as inferred from binding of [11C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB), a second generation SERT radioligand, in subcortical and cerebral cortical brain areas of clinically advanced non-depressed (confirmed by structured psychiatric interview) patients with PD. SERT binding levels in PD were lower than those in controls in all examined brain areas, with the changes statistically significant in orbitofrontal cortex (-22%), caudate (-30%), putamen (-26%), and midbrain (-29%). However, only a slight non-significant reduction (-7%) was observed in dorsolateral pre-frontal cortex, an area implicated in major depression. Our imaging data suggests that a modest, regionally widespread loss of brain serotonergic innervation might be a common feature of advanced PD. Further investigation will be required to establish whether SERT binding is more or less decreased in those patients with PD who also have major depressive disorder.

Bilateral deep brain stimulation in Parkinson's disease: a multicentre study with 4 years follow-up.

Deep brain stimulation (DBS) is associated with significant improvement of motor complications in patients with severe Parkinson's disease after some 6-12 months of treatment. Long-term results in a large number of patients have been reported only from a single study centre. We report 69 Parkinson's disease patients treated with bilateral DBS of the subthalamic nucleus (STN, n = 49) or globus pallidus internus (GPi, n = 20) included in a multicentre study. Patients were assessed preoperatively and at 1 year and 3-4 years after surgery. The primary outcome measure was the change in the 'off' medication score of the Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) at 3-4 years. Stimulation of the STN or GPi induced a significant improvement (50 and 39%; P < 0.0001) of the 'off' medication UPDRS-III score at 3-4 years with respect to baseline. Stimulation improved cardinal features and activities of daily living (ADL) (P < 0.0001 and P < 0.02 for STN and GPi, respectively) and prolonged the 'on' time spent with good mobility without dyskinesias (P < 0.00001). Daily dosage of levodopa was significantly reduced (35%) in the STN-treated group only (P < 0.001). Comparison of the improvement induced by stimulation at 1 year with 3-4 years showed a significant worsening in the 'on' medication motor states of the UPDRS-III, ADL and gait in both STN and GPi groups, and speech and postural stability in the STN-treated group. Adverse events (AEs) included cognitive decline, speech difficulty, instability, gait disorders and depression. These were more common in patients treated with DBS of the STN. No patient abandoned treatment as a result of these side effects. This experience, which represents the first multicentre study assessing the long-term efficacy of either STN or GPi stimulation, shows a significant and substantial clinically important therapeutic benefit for at least 3-4 years in a large cohort of patients with severe Parkinson's disease.

Temporal horn enlargement is present in schizophrenia and bipolar disorder.

BACKGROUND: Ventricular enlargement and temporal lobe volume deficits have been demonstrated in patients with affective disorder as well as those with schizophrenia. This study compares quantitative measures of temporal lobe, hemispheric, and ventricular volumes in a group of patients with chronic schizophrenia and bipolar disorder and seeks to determine if the groups can be differentiated on the basis of measured brain abnormalities. METHODS: A series of coronal magnetic resonance imaging sections were acquired and analyzed for each of 22 patients with chronic schizophrenia, 14 patients with bipolar disorder, and 15 community volunteers. Eleven regions of interest for each brain were defined, which included temporal lobe, superior temporal gyrus, hemisphere, lateral ventricle, third ventricle, and temporal horn measures. Tissue measures were obtained by tracing, and cerebrospinal fluid measures were obtained by fluid-tissue thresholding using specialized computer software. RESULTS: Both patient groups had significantly larger temporal horn volumes in comparison with the control group both before and after correction for intracranial volume. The two patient groups did not differ from each other or controls on any other tissue or fluid measure. CONCLUSIONS: This study confirms the findings of increased temporal horn volume in patients with schizophrenia and suggests that this structural abnormality does not differentiate the structural neuropathology of schizophrenia from that of bipolar disorder.

Anatomical organization of cortico-mesencephalo-olivary pathways in the cat as demonstrated by axonal transport techniques.

Cortical projections arising from areas 4 and 6 and terminating in midbrain cell groups known to project to the inferior olive (IO) have been studied in the cat. Injections of the bidirectional tracers horseradish peroxidase (HRP) and wheat germ agglutinin (WGA) conjugated to HRP were made into the midbrain. All cases of lateralized midbrain injections resulted in virtually ipsilateral labelling of lamina V cortical neurons. Retrogradely labelled neurons in cortical areas 4 and 6 were found after injections located in the interstitial nucleus of Cajal (INC), nucleus of Darkschewitsch (ND), and in the caudal parafascicular (Pf) and subparafascicular (sPf) nuclei (perifascicular region, PF). Injections that were more caudal and within the parvi- and magnocellular red nucleus (RNp and RNm) labelled cells not only in areas 4 and 6 but also in portions of adjacent areas 3a, 3b, 5a, and 7. These midbrain injections also resulted in the anterograde labelling of projections observed to terminate in the ipsilateral IO. The distribution in the midbrain of projections arising from cortical areas 4 and 6, and portions of areas 3a and 3b, was studied with autoradiographic methods. After injections of tritium-labelled amino acids in those cortical areas, a pattern of largely ipsilateral terminations was revealed. Whereas all cortical areas studied labelled the PF, differential grain distributions in central mesencephalic nuclei were apparent after injections in various portions of the motor and adjacent somatosensory cortex. Injections involving the frontal eye fields (FEF) labelled the INC bilaterally, but ipsilateral terminations were densest. These cases also labelled the region of the fields of Forel. When the neck region of the cortex was involved in the injections, the more caudal aspects of the INC (INCc) and the RN were labelled. The cortical areas related to the upper limb gave rise to terminations in the ND and the RNp. Contributions to both ND and RNp inputs from injections in the FEF and neck regions were also occasionally but not consistently noted. A relatively discrete injection in the vibrissae field weakly labelled ND. Additional components of the motor cortical projections to the superior colliculus (SC) and pretectal nuclei were also analysed since those regions also project to the IO. Cortical regions involving the representation of the neck musculature were shown to project principally ipsilaterally to lamina IV of the SC as well as to the anterior pretectal nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Sources of descending afferents to the inferior olive from the upper brain stem in the cat as revealed by the retrograde transport of horseradish peroxidase.

The retrograde transport of horseradish peroxidase (HRP) was employed in 35 cats to trace the sources of descending afferents to the inferior olivary nucleus. The majority of HRP-labeled cells were located in the ipsilateral mesencephalon, from the rostral pole of the red nucleus to the caudomedial border of the thalamus. Among the heavily labeled nuclear groups were the the parvocellular red nucleus, the interstitial nucleus of Cajal, the nucleus of Darkschewitsch, and the caudomedial extremity of the subparafascicular nucleus. Occasional cells were also labeled in the reticular formation lateral to the interstitial nucleus of Cajal in the caudomedial parafascicular nucleus, in the nucleus of the fields of Forel, and in the central gray. It was not possible to recognize a topographic distribution of the labeled cells corresponding to the localization of the HRP deposits. Elsewhere in the midbrain, there were HRP-labeled cells in the deep layers of the superior colliculus (IV and VI), predominantly on the side contralateral to the injection and in the nucleus of the optic tract, and in the anterior and posterior pretectal nuclei, ipsilaterally. These groups were best labeled after caudally located injections in the olive. Certain areas previously reported to project to the inferior olive were devoid of labeled cells; these included the basal ganglia, the rostral raphe nuclei, and the nucleus of Edinger-Westphal. It appears that the mesencephalic nuclei bordering the central gray represent the major source of descending afferents to the olive.

Comparative topography of projections from the mesodiencephalic junction to the inferior olive, vestibular nuclei, and upper cervical cord in the cat.

Distributions of neurons located in the central rostral mesencephalon and caudal diencephalon that project to the upper cervical spinal cord, vestibular nuclei, or inferior olive were studied in the cat by using retrograde axonal transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Afferent sources to all of these targets were observed in the interstitial nucleus of Cajal (INC), the region surrounding the fasciculus retroflexus (PF), and the nucleus of the fields of Forel (NFF). Three-dimensional reconstruction revealed differences in densities of cells projecting from these common areas. Spinal projecting cells were present in slightly greater numbers in the caudal two-thirds of the INC, whereas those projecting to the vestibular complex were more numerous in the rostral two-thirds of this nucleus. A relatively smaller number of olivary projecting cells were dispersed throughout the INC. Olivary afferent sources outnumber those with spinally directed or vestibularly directed axons in the PF region. In the fields of Forel, cells projecting to the vestibular nuclei or inferior olive were concentrated medially, whereas cells projecting to the spinal cord appeared both medially and laterally. Each type of afferent source was also seen in the nucleus of the posterior commissure and the posterior ventral lateral hypothalamic area. Unique sources of afferents to the inferior olive were observed in the parvicellular red nucleus (ipsilateral to the injections) and the anterior and posterior pretectal nuclei. A large number of labeled neurons was seen in the nucleus of Darkschewitsch after injections of tracer into the inferior olive, but this projection did not appear to be unique, as small numbers of labeled cells were also seen after injections into the cervical spinal cord. The Edinger-Westphal nucleus and the adjacent somatic oculomotor nucleus contained cells which projected separately to the spinal cord or the vestibular complex, and the superior colliculus contained cells which projected separately to the contralateral spinal cord or the contralateral inferior olive. In this study, it was also noted that neurons in the medial terminal nucleus of the accessory optic tract projected to the ipsilateral inferior olive or to the contralateral vestibular complex. These differences in locations and densities of cells projecting to the cervical spinal cord, vestibular complex, and inferior olive may underlie functional specializations in these areas in relation to vertical eye and head movement control and to neural systems controlling postural adjustments accompanying limb movements.

Mesodiencephalic projections to the vestibular complex in the cat.

The distribution of cells in the rostral medial mesencephalon and caudal diencephalon which project to the vestibular complex was mapped in the cat by using retrograde axonal transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Subsequent experiments using anterograde transport of WGA-HRP clarified the position of the terminations of the mesodiencephalic-derived afferents in the vestibular complex. After large injections which involved the entire vestibular complex, retrogradely labeled cells were seen in both the ipsilateral and contralateral interstitial nucleus of Cajal (INC) and were more numerous in its rostral pole. Labeled cells also occurred in the perifascicular region, both immediately adjacent to the fasciculus retroflexus and rostroventral to it. Fusiform midline cells of the Edinger-Westphal nucleus were also labeled, as well as a number of cells in the adjacent somatic portion of the oculomotor complex (OMC). Another group of labeled cells was observed within the contralateral medial terminal nucleus of the accessory optic tract (MTN) and in the posterior hypothalamic nucleus. Injections limited to subregions of the vestibular complex resulted in similar but slightly varying distributions and numbers of retrogradely labeled cells. After injections covering the caudal half of the medial vestibular nucleus (MVN) and descending vestibular nucleus (DVN), labeled cells in the INC and tegmentum dorsal to it were especially prominent, but none was seen in the MTN or OMC. Injections placed in the rostral MVN, lateral vestibular nucleus, y group, and superior vestibular nucleus resulted in a distribution of labeled cells similar to that seen following global vestibular injections, but these cells were fewer in number. After an injection confined to the y group, a small number of retrogradely labeled cells were seen in the rostral pole of the INC and immediately ventral to the fasciculus retroflexus. Projections from the rostral medial mesencephalon and caudal diencephalon to the MVN, DVN, and y group were confirmed by using anterograde transport of WGA-HRP. Direct projections from the INC-perifascicular regions and somatic neurons of the OMC to the caudal vestibular complex could play a role in eye-head coordination. Those projections from the rostral INC and MTN to the rostral vestibular complex may play a role in vertical eye movements and responses to visual stimuli which move in the vertical plane.

Organization of spinal inputs to the perihypoglossal complex in the cat.

First- and second-order spinal afferents to the perihypoglossal complex were sought by using axonal transport of WGA-HRP. Injections in C1, 2, and 3 dorsal root ganglia resulted in axonal labeling in the nucleus intercalatus and the external cuneate nucleus, with a number of retrogradely labeled cells seen as well in the latter. A similar pattern of axonal labeling in the nucleus intercalatus as well as several retrogradely labeled cells were found after spinal cord injections at levels C1, 2, and 3. A prominent field of labeled axons was also present in the rostral main cuneate nucleus. No labeling was seen in the perihypoglossal nuclei after injections in the spinal cord or dorsal root ganglia at levels caudal to C3. After injections of HRP into the perihypoglossal nucleus we were able to identify labeled neurons within Rexed's laminae V-VIII and the central cervical nucleus. Anterograde labeling in the main cuneate nucleus was observed after C1 to C5 ganglion and C1 to C6 cord injections. The pattern and extent of labeling in the perihypoglossal nuclei and adjacent structures seen after cerebellar injections into lobules V and VI were comparable to those previously reported and permitted evaluation of the relay from dorsal root ganglia through the intercalatus to the vermis. Topography of the cervical projections to the nucleus intercalatus is considered with respect to that of the perihypoglossal-collicular projection. A discussion is offered of the apparent importance of nucleus intercalatus as a relay of cervical and vestibular afferent information to premotor structures involved in neck motor control. The perihypoglossal complex is viewed as being organized in such a fashion as to allow the nuclei intercalatus and prepositus hypoglossi to function as key structures in the integration of inputs related to neck and ocular motor control, respectively.

Morphological alterations in rat CA1 hippocampal pyramidal cell dendrites resulting from chronic ethanol consumption and withdrawal.

Hippocampal CA1 pyramidal cell dendrites were studied in rats after 5 months of consumption of an ethanol liquid diet and 5 months of ethanol diet followed by 2 months of withdrawal. Morphometric data were compared with those obtained from matched littermate, yoke -fed control animals. Dendritic branching in Golgi-Cox-stained tissues was assessed by standard and modified Sholl analysis techniques and basilar dendrites were analysed three-dimensionally by computer. Five months of chronic ethanol consumption caused a significant decrease in the number of second-order basilar dendrites, 60-90 micron from the apical border of the cell layer. No significant changes in the neuronal density of CA1 or CA3 cells were found; however, the thickness of the strata oriens and radiatum of the CA1 field was significantly decreased in the ethanol-fed group. After 5 months of chronic ethanol consumption and 2 months of withdrawal, the thickness of the strata returned to control sizes and the frequency of proximal basilar branching recovered. Evidence of lengthening and new branching of distal basilar dendrites occurred in the third-, fourth-, and fifth-order segments when control animals 6 and 8 months of age were compared. During the 2-month period of withdrawal, the number and length of third-, fourth-, and fifth-order segments of basilar dendrites increased when compared to the nonwithdrawn ethanol group while the number and length of second- and third-order segments decreased. This is comparable to the changes seen during normal aging and suggests that withdrawal may interact with aging to produce enhanced dendritic growth in "compensation" for the developmental retardation induced by chronic ethanol intake.

Organization of visual cortical inputs to the striatum and subsequent outputs to the pallido-nigral complex in the monkey.

To determine the organization of visual inputs and outputs of the striatum, we placed multiple retrograde and anterograde tracers into physiologically identified portions of the striatum known to receive inputs from visual cortex in seven macaques. The injection sites included the tail and genu of the caudate nucleus (14 cases), the head of the caudate (1 case), and the ventral putamen (3 cases). Retrogradely labeled cells were located predominantly in layer 5 of the ipsilateral cortex but were also found in layers 3 and 6. After caudate injections, labeled cells were found both in large, nearly continuous regions of cortex topographically related to the site of the injection, and in several smaller cortical regions that were discontinuous and common to many or all of the injection sites. The continuously labeled regions included nearly all known visual cortical areas, except for the striate cortex. After injections in the rostral tail, the continuously labeled region included the rostral portion of Bonin and Bailey's (Urbana: University of Illinois Press. '47) area TE and adjacent portions of TF, TH, TG, and, occasionally, area 35 (Brodmann, Leipzig: J.A. Barth. '09). After injections into the posterior tail and ventral genu, the labeled region shifted posteriorly in TE and TF, and into TEO and the ventral parts of prestriate areas V4, V3, and (sparsely) V2. As the injection site was advanced into the dorsal genu, the labeled region shifted dorsally toward the parietal lobe, including prestriate areas MT and PO, parietal area PG (Brodmann's area 7), the ventral and lateral intraparietal sulcal areas (VIP and LIP, respectively), and area PE and adjacent area LC (Brodmann's areas 5 and 23, respectively). The discontinuous areas labeled by many different injections included the principal sulcus/frontal eye field region, the anterior cingulate cortex, and the superior temporal polysensory area. Thus, whereas temporal, occipital, and parietal visual cortical areas project into the caudate largely according to proximity, certain multimodal cortical areas seem to have a much wider projection. To determine whether visual cortical areas have additional projections to the caudate beyond the territory of our retrograde injection sites in the tail and genu. 3H-labeled amino acids were injected into areas TE, V4, and MT in three additional monkeys. The topographic location of label in the tail and genu of the caudate in these cases was consistent with the results from injections of retrograde tracers into the caudate.(ABSTRACT TRUNCATED AT 400 WORDS)

Neuropsychological and psychiatric side effects in the treatment of Parkinson's disease.

All medications currently used to treat Parkinson's disease carry some risk of causing confusion, hallucinations, or disruption of such higher-order mental operations as problem-solving and learning. Although the elderly demented patient is at greatest risk, such complications have also been noted during treatment of younger patients. Treatment with anticholinergics may lead to a confusional state and decreased memory function in some patients, especially the elderly and those with preexisting dementia. Monoamine oxidase inhibition is considered quite benign when used alone, but may potentiate certain side effects when used in combination with other compounds. Ergot alkaloid medication, which is usually combined with levodopa, often induces severe psychiatric complications. Typical findings with levodopa treatment indicate little or no positive impact on cognition, apart from nonspecific arousal and alleviation of concomitant depressive affect. Guidelines for the management of neuropsychological and psychiatric side effects are suggested.

Neuropsychological consequences of posteroventral pallidotomy for the treatment of Parkinson's disease.

OBJECTIVE: Neuropsychological changes were assessed in patients who had idiopathic PD after unilateral posteroventral pallidotomy. METHODS: Posteroventral stereotactic pallidotomies were performed on 42 PD patients (24 right and 18 left hemisphere). All patients were evaluated in the "on state" before the procedure (n = 42) and at intervals of 3 (n = 26), 6 (n = 27), and 12+ (n = 24) months after surgery. RESULTS: Modest improvement in sustained attention and decline in working memory was observed by 6 months after surgery. Left hemisphere lesions led to a loss of verbal learning (-2.2 SD) and verbal fluency (-1.6 SD) in 60% of patients at their first evaluation at 3 or 6 months. No patients returned to baseline on the verbal fluency task and most (71%) did not recover verbal-learning ability by 12 months after surgery. Right hemisphere lesions led to a loss of visuospatial constructional abilities (-3.5 SD), which fully resolved by 12 months for all but one patient. Evidence of further decline of frontal-executive functioning was noted within other tasks but not on a "direct" test (i.e., Conditional Associative Learning). Lastly, behavioral changes of a "frontal nature" were reported in 25% to 30% of patients. These cognitive and emotional costs increased dependence in these domains and negatively affected some patients' relations with caregivers and restricted their ability to function properly at work or in social settings. Caregivers, particularly, and patients who were aware of their resulting changes had difficulty adjusting after surgery. CONCLUSIONS: Although patients and caregivers were generally pleased with the clinical neurologic outcome of the procedure, the neurologic benefits of unilateral pallidotomy must be weighed against modest cognitive and behavioral risks.

The projection from the motor cortex to the inferior olive in the cat. An experimental study using axonal transport techniques.

The cortico-olivary projection has been investigated in the cat with the methods of retrograde transport of horseradish peroxidase and wheat-germ agglutinin conjugated with horseradish peroxidase as well as autoradiographic techniques using tritium-labelled amino acids. The projection arises from cells in cortical layer V and terminates mainly ipsilaterally and less densely contralaterally. The strongest termination site is in the caudal medial accessory olive adjacent to subnucleus beta. Projections to that area originate in the medial portions of areas 4 and 6 rostral to the cruciate sulcus. Regions of the motor cortex related to axial back and neck, proximal forelimb and face musculature plus the frontal eye field are represented in largely overlapping areas of the caudal medial accessory olive. A second zone of termination is present in the rostral olive at the junction of the ventral lamella of the principal olive and the medial border of the dorsal accessory olive. Projections to that area arise from a central portion of area 4 at the border between the anterior sigmoid gyrus and the presylvian gyrus. This area contains portions of the representation of the muscle groups controlling the neck and proximal forelimb (shoulder and elbow) only. The frontal eye field, which in the cat influences both extraocular and neck musculature, is also an important direct source of input to this portion of the inferior olive. Contralateral terminations are distributed symmetrically. Combining this information with the olivocerebellar distribution, cerebellar cortical areas corresponding to this direct cortical input are defined. Taking into account that the cortico-olivary fibers appear to arise only from those portions of the motor cortex involved in the control of axial and proximal forelimb muscles, it is suggested that the cortico-olivo-cerebellar projections play a preponderant role in the cerebellar control of posture.

Differential neuronal activity in segments of globus pallidus in Parkinson's disease patients.

Microelectrode trajectories through the globus pallidus of 6 Parkinson's disease (PD) patients yielded neurophysiological 'landmarks' which enabled the identification of neurones located in the external segment (GPe) and internal segments, exterior (GPi,e) and interior (GPi,i) of globus pallidus and the surrounding borders (Bor). Firing rate histograms and inter-spike interval time histograms were constructed for neurones in each region. The neuronal activity in GPi,i was higher than in the other segments, and a high degree of bursting was found in GPe and GPi neurones. This profile of neuronal activity is similar to that observed in monkeys treated with MPTP, suggesting that the observed level of activity of neurones in GPi,i is excessive, and contributes to the bradykinesia and rigidity of PD patients.

A transcervical surgical approach to the ventral medulla of the cat.

For the purpose of injection of anatomical tracers, it is desirable to have a surgical approach which provides the most direct approach to the target structure. This minimizes the amount of neural tissue that must be transgressed, and hence the leakage of tracer along the tract and the potential undesirable labelling that may result from this. In addition, visual guidance is preferable to stereotaxic guidance of injections where possible, particularly in situations where the target structure is far removed from the ear bar zero coordinate. Some of our work has necessitated small, discrete injections in the inferior olive sparing the adjacent reticular formation. The ventral transcervical approach to the medulla which was developed for this purpose is described below. It may conceivably be of use to physiologists wishing to record from ventral medullary structures. We feel it is a useful technique, but one which those with little surgical experience might not attempt. It is hoped that our description may guide others who could benefit by this approach.

Efferent projections of the anteromedial cortex of the rat as described by Phaseolus vulgaris leucoagglutinin immunohistochemistry.

Phaseolus vulgaris leucoagglutinin (PHA-L) immunohistochemistry was used to describe the corticofugal projections of the anteromedial cortex (AMC) of rats. PHA-L was injected iontophoretically into an area of the AMC which, when stimulated electrically, is known to induce contraversive head and body movements. It was found that the AMC innervates the midbrain via three separate pathways: a dorsal transthalamic pathway terminating in the pretectum, superior colliculus, and central grey area; and a ventral transthalamic pathway and a ventral capsular-peduncular pathway projecting to the central grey and mesencephalic and pontine reticular formation. The strongest terminations were found bilaterally in the mediodorsal thalamic nucleus and nucleus caudato-putamen. The functional significance of the pathways and terminations is discussed.

Projection from the vestibular nuclei to the inferior olive in the cat: an autoradiographic and horseradish peroxidase study.

Injections of horseradish peroxidase (HRP) in the inferior olive of 13 cats resulted in the labeling of neurons in the medial (MVN) and descending vestibular nuclei (DVN) as well as in subgroups g, p.h., s.v., x and z. The contribution of groups p.h. and z. could not be definitively established. Injections of triated leucine in the vestibular nuclei and adjacent reticular formation in 4 cats indicated that the previously identified vestibular nuclei and subgroups project bilaterally to the dorsomedial cell column and ipsilaterally to subnucleus beta of the inferior olive. In view of the known topography of olivocerebellar projections, the present results suggest that climbing fiber-mediated vestibular information may influence the uvula and the fastigial nucleus.

Ethanol-induced dendritic alterations in hippocampal granule cells.

The effects of chronic ethanol intake were studied on the morphology of rat hippocampal granule cells. Sprague-Dawley rats were exposed to ethanol in a liquid diet for 5 months followed by a 3 week withdrawal period. A control group was fed similar amounts of the same diet but with ethanol replaced by maltose-dextrins. Intracellular recordings were performed using the hippocampal slice preparation and the granule cells from animals of both groups were injected with HRP. The ethanol treatment produced a significant increase in the average length of the dendrites of granule cells compared to the control group. Chronic ethanol intake produced a decrease in the number of dendrites in the proximal region of the tree (80-180 microns) but also a significant increase in the number of dendrites in the distal portion (260-340 microns). The decrease in the number of proximal dendrites suggests that ethanol could be affecting a population of neurons with afferent inputs in the proximal region of the tree or that ethanol could interfere with the normal maturation processes of the granule cells. The increase in the number of dendrites in the distal region of the tree suggests, however, an accelerated growth or sprouting of dendrites in the molecular layer.

Assessment of spinal cord injury by counting corticospinal and rubrospinal neurons.

This paper describes an objective, quantifiable technique for assaying the degree of severity of spinal cord injury. Twenty-one rats underwent a C7-T1 laminectomy: 12 received a C8 spinal cord clip compression injury with forces of either 2.3, 16.9 or 53.0 g; 4 had cord transection at C8, and 5 had no cord lesion. Postoperative clinical neurological assessment was performed by the inclined plane method. At 4 weeks, the spinal cord-injured rats underwent a T10 transection and insertion of a Gelfoam pledget impregnated with horseradish peroxidase (HRP). HRP was similarly administered to 9 normal rats. Longitudinal sections of the spinal cord encompassing the injury site were stained with Luxol fast blue, and coronal sections from the cerebrum and midbrain were processed for HRP reactivity with tetramethylbenzidine. Labelled corticospinal and rubrospinal neurons were counted in every 6th section to derive a cortical score (CS) and a red nucleus score (RNS) for each animal. The CS reflected the extent of the pathological changes at the site of cord injury and the ln CS decreased linearly with increasing injury severity (P less than 0.0001). In contrast, the RNS was only reduced in animals with severe (53.0 g) cord injuries (P less than 0.0006). The degree of preservation of the dorsal columns including the corticospinal tracts at the injury site correlated with the CS, whereas the RNS was related to the degree of preservation of the lateral columns. Counts of rubrospinal neurons, but not corticospinal neurons, correlated closely (r = 0.96, P less than 0.001) with the inclined plane results, suggesting the importance of non-pyramidal tracts in controlling gross motor function. Thus, counting corticospinal and rubrospinal neurons is an objective, reliable test of the severity of experimental spinal cord injury.

Posteroventral medial pallidotomy in Parkinson's disease.

There has been a resurgence in the use of functional neurosurgery for Parkinson's disease. An important factor that has played a role in this development is the recent understanding of the functional anatomy of the basal ganglia including a knowledge of the changes in the activities of neurons in the internal segment of the globus pallidus (Gpi) and the subthalamic nucleus (STN) in Parkinson's disease as well as the knowledge of the presence of segregated functional loops within the basal ganglia which include a sensory-motor loop that involves the posteromedial globus pallidus rather than the anterior GPi where earlier pallidotomy lesions had been made. Laitinen reintroduced the modern posteroventral medial pallidotomy (PVMP) in 1992. Since then it has become clear that this treatment has major effects on levodopa-induced dyskinesias and, unlike Vim thalamotomy, improves bradykinesia and rigidity as well as tremor. In this report, we review a number of topics related to PVMP including the clinical results of pallidotomy available in the literature as well as an update of our own 2 year follow-up data, studies evaluating factors that might predict the subsequent response to pallidotomy, the neuropsychological effects of the procedure, results of imaging studies including the correlation of clinical effects with lesion location, the question of bilateral pallidotomy and pallidotomy combined with deep brain stimulation and finally whether PVMP is effective in other parkinsonian disorders.