Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Internal Capsule”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,009 records · Page 56Linked to original sources
PubMed1995

Stroke in purine nucleoside phosphorylase deficiency.

The first documented case of cerebrovascular disease occurring in a 13-year-old girl with purine nucleoside phosphorylase deficiency is reported. This patient, the oldest known survivor with purine nucleoside phosphorylase deficiency, had previously experienced multiple sequential neurologic problems. She presented with episodes of transient left hemiparesis, followed shortly thereafter by dense left hemiplegia. Magnetic resonance imaging revealed a right internal capsule infarct; cerebral angiography revealed vasculopathy of the proximal vessels. Proposed mechanisms for neurologic dysfunction and cerebrovascular disease in purine nucleoside phosphorylase deficiency are discussed.

Adolescent↗
PubMed1994

Tonic "seizures" in a patient with brainstem demyelination: MRI study of brain and spinal cord.

Tonic seizures are a poorly understood manifestation of demyelinating disease, first reported in 4 patients with multiple sclerosis. We describe a patient with tonic extension of the left limbs caused by a right-sided brainstem lesion as the first manifestation of demyelinating disease. A 19-year-old man was referred with a 4-month history of spontaneous attacks of mild paresthesias of the left arm and leg, followed by 15-45 s of rigid extension of the left limbs, occurring up to 25 times per day. Two months after onset, an MRI scan revealed areas of T2 abnormality in the lateral right cerebral peduncle and deep frontal white matter. The EEG was normal, including during hyperventilation which induced a typical episode. All attacks were successfully suppressed by carbamazepine, phenytoin, and valproate monotherapy. Serologic testing for toxoplasmosis, cytomegalovirus, Epstein-Barr virus, Lyme disease, and HIV was negative. Cerebrospinal fluid oligoclonal bands were absent but cerebrospinal fluid immunoglobulin G was mildly elevated (4.2 mg/dl). Over the next 30 months, serial MRIs revealed a normal spinal cord and persistence of the midbrain lesion, with resolution of some of the white matter lesions but reappearance of others. At 46 months, the midbrain lesion resolved on MRI, and the spasms no longer occurred spontaneously, nor could they be elicited by hyperventilation. While two previous reports have shown internal capsule lesions to underlie the tonic spasms in demyelinating disease, this is the first report in which a brainstem lesion has been causative.

Adult↗
PubMed2005

Secondary mania of vascular origin in elderly patients: a report of two clinical cases.

The concept of secondary mania continues to be debated together with unresolved or partially resolved issues such as lateralization, localization, age of onset, disinhibition syndromes, and others. We have described two patients with secondary mania following a stroke. One had a large left hemisphere cerebral infarction and the symptoms arose about 2.5 years later, possibly triggered by a transient ischemic attack involving the right hemisphere. The other had an infarction in the right posterior artery territory extending to the thalamus and internal capsule together with infarctions in the deep border zones of both hemispheres at the level of the centrum semiovale with the manic symptoms concomitant with the onset of the event. The clinical and neuro-anatomic mechanisms that underlie the diverse locations of secondary mania are discussed. The cerebral components of secondary mania and disinhibition syndromes are very similar and it is proposed that disinhibition syndromes, secondary hypomania and secondary mania with and without psychotic symptoms are simply a continuum of severity of mood disorder and secondary mania with psychotic symptoms may be an extreme form. The concept of secondary mania in the elderly is not likely to disappear although several unresolved issues remain. For the neurophysician, geriatrician, and the psychiatrist there is much to be attained by simplifying the issues and accepting the view that secondary mania is a discrete entity.

Aged↗
PubMed2005

Deep brain stimulation for refractory obsessive-compulsive disorder.

BACKGROUND: Neurosurgery (anterior capsulotomy) has been beneficial to many patients with debilitating, refractory obsessive-compulsive disorder (OCD), but the irreversibility of the procedure is an important limitation to its use. Nondestructive, electrical stimulation (deep brain stimulation; DBS) has proven an effective alternative to ablative surgery for neurological indications, suggesting potential utility in place of capsulotomy for OCD. METHODS: The effects of DBS for OCD were examined in four patients in a short-term, blinded, on-off design and long-term, open follow-up. The patients had incapacitating illness, refractory to standard treatments. Hardware developed for movement disorder treatment was surgically implanted, with leads placed bilaterally in the anterior limbs of their internal capsules. Patients received stimulation in a randomized "on-off" sequence of four 3-week blocks. Ongoing, open stimulation was continued in consenting patients after the controlled trial. RESULTS: Patients tolerated DBS well. Dramatic benefits to mood, anxiety, and OCD symptoms were seen in one patient during blinded study and open, long-term follow-up. A second patient showed moderate benefit during open follow-up. CONCLUSIONS: It appears that DBS has potential value for treating refractory psychiatric disorders, but additional development work is needed before the procedure is utilized outside of carefully controlled research protocols.

Adult↗
PubMed2005

Fronto-thalamo-striatal gray and white matter volumes and anisotropy of their connections in bipolar spectrum illnesses.

BACKGROUND: Neurons in the basal ganglia are connected to areas of prefrontal cerebral cortex involved in higher cognitive functions, and these connections occur primarily via the thalamus. In patients with bipolar disorder, regardless of age, neuroimaging studies have consistently reported an increased number of white matter hyperintensities, indicating possible alterations in striatum-thalamus and thalamus-prefrontal cortex connections. METHODS: In the current study, we acquired high-resolution magnetic resonance imaging (MRI) and diffusion tensor (DT) scans of 40 patients with bipolar spectrum (BPS) illnesses (bipolar type I = 17, bipolar type II = 7, cyclothymia = 16) and 36 sex- and age-matched control subjects. Two researchers, without knowledge of diagnosis, outlined the caudate, putamen, and thalamus on contiguous axial MRI slices. We measured the volumes of the basal ganglia, thalamus, and gray/white matter of the frontal cortex. RESULTS: Bipolar spectrum patients as a single group did not differ from control subjects in thalamus and the basal ganglia volumes, but the cyclothymia patients had reductions in the volumes of putamen and the thalamus compared with control subjects. The BPS patients had significantly reduced volume of the white and the gray matter of the frontal cortex. Furthermore, compared with control subjects, BPS patients as a group showed alterations in anisotropy of the internal capsule adjacent to the striatum and thalamus and the frontal white matter. CONCLUSIONS: Our findings indicate that BPS patients may have distinct anatomical alterations in brain structures involved in the regulation of mood and cognition, as well as alterations in these structures' connection to related brain areas.

Adult↗
PubMed2005

The prefrontal substrate of reflexive saccade inhibition in humans.

BACKGROUND: Prefrontal dysfunction in neuropsychiatric disorders such as schizophrenia has been shown to impair inhibition of reflexive saccadic eye movements; however, it is unclear whether reflexive saccade inhibition can be attributed to a distinct subregion of the human prefrontal cortex. METHODS: We tested 15 patients with acute unilateral ischemic lesions of the prefrontal cortex and 20 control subjects with an antisaccade task. Lesions were reconstructed using Talairach coordinates, and possible candidate regions for reflexive saccade inhibition were identified. RESULTS: Significantly increased antisaccade error rates were observed in patients with lesions affecting a region in mid-dorsolateral prefrontal cortex or the white matter between this region and the anterior portions of the internal capsule. Antisaccade error rates of patients with lesions outside this region were normal. These findings were largely independent of lesion volume, postlesion delay, and subject age. CONCLUSIONS: Our findings suggest that inhibition of reflexive saccades depends on a circumscribed subregion of the human dorsolateral prefrontal cortex. This region closely corresponds to Brodmann area 46 as defined by recent cytoarchitectonic studies. Increased antisaccade error rates in patients with prefrontal pathology may be explained by dysfunction of this region.

Aging↗
PubMed2006

Dorsolateral prefrontal cortex and anterior cingulate cortex white matter alterations in late-life depression.

BACKGROUND: The dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) are critical for mood regulation. Alterations in the white matter connections of these regions may impair their role in mood regulation and increase the risk of developing depression. This study used diffusion tensor imaging to examine for white matter microstructural abnormalities of these regions and of central white matter structures in late-life depression. METHODS: One hundred six elderly depressed subjects and eighty-four elderly nondepressed subjects underwent clinical assessment and diffusion tensor imaging. The apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in regions of interest placed in the white matter of the DLPFC, ACC, corpus callosum, and internal capsule. Differences between groups were assessed, controlling for age, sex, and total cerebral volume. RESULTS: After controlling for covariates, depressed subjects had significantly lower FA values in white matter of the right ACC, bilateral superior frontal gyri, and left middle frontal gyrus. There were no significant differences in ADC values. CONCLUSIONS: Lower FA, representing lower tissue organization, is observed in depressed elders in the DLPFC and right ACC. These findings support the hypothesis that altered connectivity between brain regions contributes to the risk of depression.

Aged↗
PubMed2003

Ibudilast, a phosphodiesterase inhibitor, protects against white matter damage under chronic cerebral hypoperfusion in the rat.

Cerebrovascular white matter (WM) lesions, which are frequently observed in vascular cognitive impairment and vascular dementia, can be produced in rats by clipping the common carotid arteries bilaterally. Since TNF-alpha is known to cause the degeneration of myelin, we examined whether these lesions can be ameliorated by ibudilast, a cyclic AMP phosphodiesterase (PDE) inhibitor that suppresses tumor necrosis factor (TNF)-alpha production. After the ligation of both common carotid arteries in 29 rats, 21 rats received a daily oral administration of 10, 30 or 60 mg/kg ibudilast and 8 rats received vehicle for 14 days. The pathological changes in the white matter were quantified in terms of white matter lesions and the emergence of activated microglia immunoreactive for major histocompatibility complex (MHC) antigen. In the vehicle-treated animals, white matter lesions and microglial activation occurred in the optic tract, internal capsule and corpus callosum. A low dose (10 mg/kg) of ibudilast failed to suppress the white matter lesions and microglial activation, whereas a dose of either 30 or 60 mg/kg ibudilast ameliorated these lesions (p<0.001). Without an alterations in laboratory blood data, 60 mg/kg ibudilast exhibited percent reduction of the white matter lesions ranging between 50% and 70%, which was more effective than 30 mg/kg ibudilast (p<0.05). The TNF-alpha immunoreactive glia decreased in number in the 60 mg/kg ibudilast-treated group as compared to the vehicle-treated group (p<0.001). These results indicate a dose-dependent protective effect of ibudilast against cerebrovascular white matter lesions and suggest a potential use for ibudilast in the treatment of vascular dementia.

Administration, Oral↗
PubMed2004

alpha-Phenyl-n-tert-butyl-nitrone attenuates hypoxic-ischemic white matter injury in the neonatal rat brain.

White matter of the neonatal brain is highly sensitive to hypoxic-ischemic insult. The susceptibility of premature oligodendrocytes (OLs) to free radicals (FRs) produced during hypoxia-ischemia (HI) has been proposed as one of the mechanisms involved. To test this hypothesis, and to further investigate if the FR scavenger alpha-phenyl-N-tert-butyl-nitrone (PBN) attenuates hypoxic-ischemic white matter damage (WMD), postnatal day 4 (P4) SD rats were subjected to bilateral common carotid artery ligation (BCAL), followed by 8% oxygen exposure for 20 min. Pathological changes were evaluated on P6 and P9, 2 and 5 days after the HI insult. HI caused severe WMD including rarefaction, necrosis and cavity formation in the corpus callosum, external and internal capsule areas. OL injury was evidenced by degeneration of O4 positive OLs on P6. Disrupted myelination was verified by decreased immunostaining of myelin basic protein (MBP) on P9. Axonal injury was demonstrated by increased amyloid precursor protein (APP) immunostaining on both P6 and P9. Two lipid peroxidation end products, malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), showed a one-fold elevation within 1-24 h following HI. 4-HNE immunostaining was found to specifically localize in the white matter area. Furthermore, pyknotic O4+ OLs were double-labeled with 4-HNE. These findings suggest that FRs are involved in the pathogenesis of neonatal WMD. PBN (100 mg/kg, i.p.) treatment alleviated the pathological changes of WMD following HI. It improved the survival of O4 positive OLs, attenuated hypomyelination and reduced axonal damage. PBN treatment also decreased the brain concentration of MDA/4-HNE and positive 4-HNE staining in the white matter area. These findings indicate that in the current WMD model, PBN protects both OLs and axons, the two main components in the white matter, from neonatal HI insult. FR scavenging appears to be the primary mechanism underlying its neuroprotective effect.

Age Factors↗
PubMed2005

Histopathological effects of delayed reperfusion after middle cerebral artery occlusion in the anesthetized baboon.

In patients with middle cerebral artery (MCA) territory stroke, attempts to recanalize the brain are currently being extended beyond the classic 3-h time window. Mechanical thrombectomy is particularly attractive as it may carry lesser risks of severe hemorrhagic transformation than thrombolysis. However, whether late reperfusion per se promotes hemorrhagic transformation and increases infarct volume as compared to permanent occlusion is unclear. There is no study of the histopathologic sequelae of late reperfusion following MCA occlusion (MCAo) in the non-human primate. Five young adult baboons completed a specially designed protocol of 20-h MCAo (under etomidate anaesthesia), followed by 4-week survival and finally perfusion-fixation. Infarct volume was measured histologically using validated stereological methods. The results were compared to our previously published series of 6 h and permanent MCAo performed with identical experimental and post mortem procedures. An infarct was present in each baboon, consistently involving the caudate head, internal capsule and putamen; the adjacent inferior frontal cortex was involved in one subject. Infarct volume was significantly larger than with 6 h MCAo, as expected, but did not differ from permanent MCAo. There was no evidence of hemorrhage around the infarcted area in any animal. We found that following a 20 h ischemic episode, the infarct volume was similar to that found with permanent occlusion, with no evidence of hemorrhagic transformation. Cautiously extrapolating to the human situation, our findings suggest that even late mechanical recanalization may not promote brain damage and could be considered in selected cases.

Anesthesia↗
PubMed2004

Electric field and stimulating influence generated by deep brain stimulation of the subthalamic nucleus.

OBJECTIVE: The goal of this project was to develop a quantitative understanding of the volume of axonal tissue directly activated by deep brain stimulation (DBS) of the subthalamic nucleus (STN). METHODS: The 3-dimensionally inhomogeneous and anisotropic tissue medium surrounding DBS electrodes complicates our understanding of the electric field and tissue response generated by the stimulation. We developed finite element computer models to address the effects of DBS in a homogeneous isotropic medium, and a medium with tissue conductivity properties derived from human diffusion tensor magnetic resonance data. The second difference of the potential distribution generated in the tissue medium was used as a predictor of the volume of tissue supra-threshold for axonal activation. RESULTS: The model predicts that clinically effective stimulation parameters (-3 V; 0.1 ms; 150 Hz) result in activation of large diameter (5.7 microm) myelinated axons over a volume that spreads outside the borders of the STN. The shape of the activation volume was dependent on the strong dorsal-ventral anisotropy of the internal capsule, and the moderate anterior-posterior anisotropy of the region around zona incerta. CONCLUSIONS: Small deviations ( approximately 1 mm) in the electrode position within STN can substantially alter the shape of the activation volume as well as its spread to neighboring structures. SIGNIFICANCE: STN DBS represents an effective treatment for medically refractory movement disorders such as Parkinson's disease. However, stimulation induced side effects such as tetanic muscle contraction, speech disturbance and ocular deviation are not uncommon. Quantitative characterization of the spread of stimulation will aid in the development of techniques to maximize the efficacy of DBS.

Artifacts↗
PubMed2006

Potential of diffusion tensor MRI in the assessment of periventricular leukomalacia.

AIM: To investigate magnetic resonance (MR) diffusion tensor imaging (DTI) and fibre tractography in the assessment of altered major white matter (WM) fibre tracts in periventricular leukomalacia (PVL). MATERIALS AND METHODS: Twelve children (male:female = 7:5, age range 3-10 years; mean age = 6.5 years) who had suffered PVL were included in this study. Meanwhile, Twelve age-matched normal controls (male:female = 6:6, age range 4-12 years; mean age = 7.3 years) with normal MRI findings and no neurological abnormalities were recruited for comparison. DTI was performed with 15 different diffusion gradient directions and DTI colour maps were created from fractional anisotropy (FA) values and the three vector elements. To identify alteration of WM fibre tracts in patient of PVL quantitatively, FA values on diffusion tensor colour maps were compared between the patients and controls. Quantitative analysis was performed using the regions of interest (ROI) method settled on the central part of all identifiable WM fibres, including the corticospinal tract (CST) in the brainstem, middle cerebellar peduncle (MCP), medial lemniscus (ML), anterior/posterior limb of internal capsule (ICAL/ICPL), arcuate fasciculus (AF), posterior thalamic radiation (PTR), genu of corpus callosum (GCC), splenium of corpus callosum (SCC), corona radiata (CR), cingulum (CG), and superior longitudinal fasciculus (SLF). The averaged FA value of each WM fibre was measured and summarized as the mean +/- standard deviation (SD). All data were analysed by paired Student's t-test. A p-value of less than 0.05 was considered to indicate statistical significance. RESULTS: Visual investigation of WM fibre tracts showed that the ICAL, brainstem CST, ML, MCP, and external capsule (EC) was similar in controls and subjects. However, the ICPL, AF, PTR, CR, CG, SLF and corpus callosum, were all attenuated in size. All 12 cases of PVL showed a significant mean FA reduction in the ICPL, AF, PTR, CR, CG, SLF, SCC, and GCC in comparison with the ipsilateral regions of healthy controls (p<0.05). However, there were no statistically significant differences of the ICAL, ML, MCP, and brainstem CST when analysed using a two-tailed Student's t-test for paired data (p>0.01). CONCLUSION: DTI can provide more information for understanding the pathophysiology of motor disability and associated sensory handicap in PVL.

Anisotropy↗
PubMed2004

Distribution of RA175/TSLC1/SynCAM, a member of the immunoglobulin superfamily, in the developing nervous system.

RA175 is a new member of the immunoglobulin superfamily with trans interaction activity, and it plays a role as a tumor suppressor in lung carcinoma (TSLC1) and as a cell adhesion molecule promoting the formation of functional synapses (SynCAM). Little is known about the biological function of RA175/TSLC1/SynCAM neural network formation during neurogenesis. We examined the distribution and colocalization of the RA175/TSLC1/SynCAM protein with other members of the immunoglobulin superfamily such as NCAM, L1, and TAG-1 in the mouse developing nervous system. Consistent with the expression of RA175/TSLC1/SynCAM mRNA, the protein was localized in the brain neuroepithelium at embryonic day (E) 9.5, neural crest at E10.5, motor neurons at E10.5, and olfactory epithelium at E16.5. In contrast with its mRNA, the protein was intensely detected on the fasciculated axons in the floor plates, ventral root, and dorsal funiculus in the E10.5-11.5 spinal cord and colocalized with NCAM and L1 on the ventral root and dorsal funiculus and partly colocalized with TAG-1 on the commissural axons and dorsal funiculus. In the E13.5-15.5 brain, RA175/TSLC1/SynCAM colocalized with NCAM and L1 on the developing thalamocortical fibers from the internal capsule (IC) and partly colocalized with TAG-1 on the cortical efferent axons in the intermediate zone (IZ). RA175/TSLC1/SynCAM was localized on the axons of some of the cortical neurons cultured in vitro. Thus, in addition to cell adhesion activity in the neuroepithelium and the synapses, RA175/TSLC1/SynCAM may be involved in neuronal migration, axon growth, pathfinding, and fasciculation on the axons of differentiating neurons.

Animals↗
PubMed2006

Contingent and non-contingent effects of heroin on mu-opioid receptor-containing ventral tegmental area GABA neurons.

Opiate activation of mu-opioid receptors (muORs) in the ventral tegmental area (VTA) modulates gamma-aminobutyric acid (GABA) neurotransmission within the mesocorticolimbic dopamine (DA) reward system. We combined in vivo extracellular electrophysiological recordings in anesthetized and freely behaving rats with intracellular Neurobiotin filling and immunocytochemistry to characterize the effects of opiates on VTA GABA neurons, evaluate their discharge activity during opiate self-administration, and identify the cellular sites for opiate activation. We identified a subpopulation of VTA GABA neurons that was characterized by location, spike discharge profile, activation by microelectrophoretic DA, and response to internal capsule (IC) stimulation. Systemic administration of heroin or microelectrophoretic application of the selective muOR agonist [d-Ala2, N-Me-Phe4, Gly-ol]-Enkephalin (DAMGO) reduced VTA GABA neuron firing rate (heroin IC(50) = 0.35 mg/kg) and was blocked by the muOR antagonist naloxone. Heroin also reduced IC-evoked post-stimulus spike discharges, a manifestation of gap-junction-mediated electrical coupling between VTA GABA neurons. The baseline firing rate of VTA GABA neurons significantly increased (239%) following the acquisition of heroin self-administration behavior and transiently increased during each response for heroin (105%), but decreased (49%) following heroin, similar to non-contingent heroin. Electrophysiologically characterized VTA GABA neurons were filled with Neurobiotin and labeled dendrites contained plasmalemmal muOR immunoreactivity. Dually labeled muOR dendrites contained dendrodendritic appositions characteristic of gap junctions. These findings indicate that inhibition of this population of GABAergic neurons by opiates acting on dendritic muORs has implications for modulation of electrical coupling between VTA GABA neurons and dopamine (DA) neurotransmission in the VTA and terminal field regions.

Action Potentials↗
PubMed2005

Origin and immunolesioning of cholinergic basal forebrain innervation of cat primary auditory cortex.

Numerous studies have implicated the cholinergic basal forebrain (cBF) in the modulation of auditory cortical responses. This study aimed to accurately define the sources of cBF input to primary auditory cortex (AI) and to assess the efficacy of a cholinergic immunotoxin in cat. Three anaesthetized cats received multiple injections of horseradish-peroxidase conjugated wheatgerm-agglutin into physiologically identified AI. Following one to two days survival, tetramethylbenzidine histochemistry revealed the greatest number of retrogradely labeled cells in ipsilateral putamen, globus pallidus and internal capsule, and smaller numbers in more medial nuclei of the basal forebrain (BF). Concurrent choline acetyltransferase immunohistochemistry showed that almost 80% of the retrogradely labeled cells in BF were cholinergic, with the vast majority of these cells arising from the more lateral BF nuclei identified above. In the second part of the study, unilateral intraparenchymal injections of the cholinergic immunotoxin ME20.4-SAP were made into the putamen/globus pallidus nuclei of six cats. Immuno- and histochemistry revealed a massive reduction in the number of cholinergic cells in and around the targeted area, and a corresponding reduction in the density of cholinergic fibers in auditory cortex. These results are discussed in terms of their implications for investigations of the role of the cBF in cortical plasticity.

Acetylcholine↗
PubMed2003

Phenotypic expression of monoamines and GABA in the early development of human telencephalon, transient or not transient.

We review the phenotypic expression of molecules involved in monoamine and GABA neurotransmission in the developing human brain. Recent experimental reports have analyzed neurotransmitter signaling before the onset of synaptogenesis, which could act to influence early developmental events such as proliferation, migration, and differentiation of animal brain development. Such signaling may also occur in human development. The expression of molecules involved in neurotransmission in precocious human brain may reflect either the differentiation of a permanent neurotransmitter system of the adult brain or transient expression to serve specific developmental functions different from those in the adult brain. We review the changes observed in the expression of various catecholamine markers such as tyrosine-hydroxylase (TH) immunoreactivity in various neuronal populations of the developing human telencephalon. The specific transporter for serotonin, serotonin transporter (SERT) has been detected in fibers of the internal capsule (IC) during the restricted time period of 12-14 gestational weeks in humans. These serotonin-containing fibers do not correspond to serotoninergic ascending axons from the raphe nuclei. They may be the human counterpart of the thalamo-cortical axons that have been shown to uptake serotonin during the critical period of development of the sensory systems in rodents. GABA phenotypes are expressed in numerous cells of the human ganglionic eminence (GE) and cerebral wall at the end of the embryonic period proper. These results are similar to that described at comparable developmental stages in the mouse and support the hypothesis of an early migration from ganglionic progenitors in humans. But one cannot exclude a transient expression of GABA within the post-mitotic neurons, which could influence early developmental events. In conclusion, data showing the phenotypic expression of molecules in discrete areas of the brain at various points in the protracted human development require careful interpretation.

Animals↗
PubMed2006

The immunohistochemical localization of neuronal nitric oxide synthase in the basal forebrain of the dog.

The present work describes for the first time the anatomical distribution of neuronal nitric oxide synthase (nNOS) immunoreactivity and NADPH-d activity in the basal forebrain of the dog. As in other species, small, intensely nNOS-immunoreactive cells were seen within the olfactory tubercle, caudate nucleus, putamen, nucleus accumbens and amygdala. In addition, a population of mixed large and small nNOS positive cells was found in the medial septum, diagonal band and nucleus basalis overlapping the distribution of the magnocellular cholinergic system of the basal forebrain. Our results show that the distribution of NOS containing neurons in these nuclei in the dog is more extensive and uniform than that reported in rodents and primates. When double labeling of nNOS and NADPH-d was performed in the same tissue section most neurons were double labeled. However, a considerable number of large perikarya in the diagonal band and nucleus basalis appeared to be single labeled for nNOS. Thought a certain degree of interference between the two procedures could not be completely excluded, these findings suggest that NADPH-d histochemistry, which is frequently used to show the presence of NOS, underestimates the potential of basal forebrains neurons to produce nitric oxide. In addition, a few neurons mainly localized among the fibers of the internal capsule, appeared to be labeled only for NADPH-d. These neurons could be expressing a different isoform of NOS, not recognized by our anti-nNOS antibody, as has been reported in healthy humans and AD patients.

Animals↗