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PubMed2004

Alpha-adrenergic receptor (alpha(2 A )) is colocalized in basal forebrain cholinergic neurons: a light and electron microscopic double immunolabeling study.

A variety of data suggest that noradrenaline and acetylcholine may interact in the basal forebrain, however no morphological studies have addressed whether indeed cholinergic neurons express adrenergic receptors. We have investigated the presence of alpha-adrenergic receptor subtype alpha2A-AR in cholinergic neurons of the basal forebrain. Cholinergic neurons were identified with an antibody against choline acetyltransferase and the receptor with a polyclonal antibody raised against a 47 amino acid fragment of the third intracellular loop of the alpha2A-AR. For double labeling at the light microscopic level the Ni-DAB/DAB technique was used, and for electron microscopy an immunoperoxidase/immunogold method was applied. We detected the alpha2A-AR protein in cholinergic as well as in non-cholinergic neurons. Almost half of all cholinergic neurons contained this adrenergic receptor. Double-labeled neurons were distributed throughout the rostro-caudal extent of the basal forebrain cholinergic continuum, including the medial septum, vertical and horizontal diagonal band nuclei, pallidal regions, substantia innominata and the internal capsule. Non-cholinergic neurons that expressed the alpha2A-AR outnumbered cholinergic/alpha2A-AR neurons by several factors. Electron microscopy confirmed the presence of alpha2A-AR in cholinergic neurons in the medial septum, vertical and horizontal diagonal band nuclei. Gold particles (10 nm) indicative of alpha2A-AR were diffusely distributed in the cytoplasm and accumulated in cytoplasmic areas near the Golgi complex and cysterns of the endoplasmic reticulum and were associated with the cellular membranes at synaptic and non-synaptic locations. Since many of the alpha2A-AR+/non-cholinergic neurons we detected are likely to be GABAergic cells, our data support the hypothesis that noradrenaline may act via basal forebrain cholinergic and non-cholinergic neurons to influence cortical activity.

Acetylcholine↗
PubMed2002

Magnetic resonance imaging in amyotrophic lateral sclerosis.

OBJECTIVE: We aimed to investigate the importance of magnetic resonance imaging for the diagnostic process of the upper motor neuron involvement. MATERIAL AND METHODS: Fifteen patients (Group 1) who were diagnosed with amyotrophic lateral sclerosis in the neurology department of the Sisli Etfal Hospital and 20 controls (Group 2) entered the study. Magnetic resonance imaging examinations were performed in the radiology clinic of the same hospital. T2 and proton density weighted axial images were obtained. These images were evaluated by two blind radiologists. The radiologists looked for two signs: the presence of a low signal intensity at the precentral cortex and the presence of symmetrical rounded foci of high signal intensity within the internal capsule on both T2 and proton density weighted images. RESULTS: For the first sign there was no statistically significant difference between the two groups but for the latter one there was a statistically significant difference. CONCLUSION: We think that the presence of the latter sign may make it possible for the radiologists to help the clinicians further in this difficult and confusing diagnosis.

Amyotrophic Lateral Sclerosis↗
PubMed1983

Rat brain sites responsive to etorphine: analgesia and catatonia.

One hundred forty-two rats given intracerebral microinjections of 1 microgram of etorphine hydrochloride were observed for subsequent analgesia (flinch-jump technique) and catatonia (bar test). Neuroanatomical specificity of effect was demonstrated to the extent that behavioral effects did not result from injections into areas of low opiate receptor binding affinity, such as medial cerebral cortex and hippocampus, nor were positive results obtained from injections into fiber bundles, such as the corpus callosum and internal capsule. Positive results were obtained in a large number of areas, ranging from brain stem to telencephalon. Injections eliciting analgesia without catatonia were limited in number (9 animals) and were widely scattered throughout neuroanatomical loci. Microinjection more frequently elicited catatonia only (29 animals), and site of injection was limited to posterior cerebral cortex, posterior amygdala, dorsal reticular formation, and cerebral aqueduct. Dual behavioral effects were elicited in 28 of the animals and occurred most frequently upon injection into the periaqueductal gray, inferior colliculus, and cerebral aqueduct. (Injection into cerebral aqueduct produced 50% catatonia only and 50% dual effects). The study suggests that opiate-elicited analgesia and catatonia may be neuroanatomically distinct phenomena.

Animals↗
PubMed1983

Focal increases of white matter glucose utilization produced by electrical stimulation of rat motor cortex.

The right motor cortex was electrically stimulated in adult, awake rats for 45 min. Local cerebral glucose utilization (LCGU) was measured in white matter pathways with the (14C)-2-deoxyglucose method. Stimulation increased LCGU in focal regions of the right internal capsule to 51.3 mumol/100 g/min, compared to 39.8 on the control left side. Stimulation also increased LCGU in the right, medial pontine pyramidal tract to 36.2 mumol/100 g/min, compared with 27.3 on the control left side. The data demonstrate that electrical stimulation of motor cortex neurons increases LCGU 30 to 40% in the efferent myelinated axons of those neurons.

Animals↗
PubMed2003

Adeno-associated virus vector-mediated transduction in the cat brain.

Adeno-associated virus (AAV) vectors are capable of delivering a therapeutic gene to the mouse brain that can result in long-term and widespread protein production. However, the human infant brain is more than 1000 times larger than the mouse brain, which will make the treatment of global neurometabolic disorders in children more difficult. In this study, we evaluated the ability of three AAV serotypes (1,2, and 5) to transduce cells in the cat brain as a model of a large mammalian brain. The human lysosomal enzyme beta-glucuronidase (GUSB) was used as a reporter gene, because it can be distinguished from feline GUSB by heat stability. The vectors were injected into the cerebral cortex, caudate nucleus, thalamus, corona radiata, internal capsule, and centrum semiovale of 8-week-old cats. The brains were evaluated for gene expression using in situ hybridization and enzyme histochemistry 10 weeks after surgery. The AAV2 vector was capable of transducing cells in the gray matter, while the AAV1 vector resulted in greater transduction of the gray matter than AAV2 as well as transduction of the white matter. AAV5 did not result in detectable transduction in the cat brain.

Animals↗
PubMed2006

Three-year outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder.

Deep brain stimulation (DBS) of the anterior limb of the internal capsule has been shown to be beneficial in the short term for obsessive-compulsive disorder (OCD) patients who exhaust conventional therapies. Nuttin et al, who published the first DBS for OCD series, found promising results using a capsule target immediately rostral to the anterior commissure extending into adjacent ventral capsule/ventral striatum (VC/VS). Published long-term outcome data are limited to four patients. In this collaborative study, 10 adult OCD patients meeting stringent criteria for severity and treatment resistance had quadripolar stimulating leads implanted bilaterally in the VC/VS. DBS was activated openly 3 weeks later. Eight patients have been followed for at least 36 months. Group Yale-Brown Obsessive Compulsive Scale (YBOCS) scores decreased from 34.6+/-0.6 (mean+/-SEM) at baseline (severe) to 22.3+/-2.1 (moderate) at 36 months (p < 0.001). Four of eight patients had a > or =35% decrease in YBOCS severity at 36 months; in two patients, scores declined between 25 and 35%. Global Assessment of Functioning scores improved from 36.6+/-1.5 at baseline to 53.8+/-2.5 at 36 months (p < 0.001). Depression and anxiety also improved, as did self-care, independent living, and work, school, and social functioning. Surgical adverse effects included an asymptomatic hemorrhage, a single seizure, and a superficial infection. Psychiatric adverse effects included transient hypomanic symptoms, and worsened depression and OCD when DBS was interrupted by stimulator battery depletion. This open study found promising long-term effects of DBS in highly treatment-resistant OCD.

Adult↗
PubMed1986

Subcortical crossed aphasia: a case report.

A 74-year-old, right-handed woman suffered acute aphasia and left hemiplegia secondary to a cerebral infarction in the right cerebral hemisphere. The lesion was located deep in the parietal lobe and extended to the posterior limb of the internal capsule and the head of the caudate nucleus. The patient's aphasia was characterized by severe impairment in auditory and visual comprehension and auditory retention span, as well as by anomia, agraphia, and dyscalculia. She showed rapid recovery from her aphasia, with residual deficits in writing, naming, calculation, and memory.

Aged↗
PubMed2002

Increased c-Fos protein in the brains of scrapie-infected SAMP8, SAMR1, AKR and C57BL mice.

Scrapie is a neurodegenerative disease that occurs naturally in sheep and goats. The histopathological changes include vacuolation, neuronal apoptosis and astrocytosis. The mechanisms involved in neuronal apoptosis are still unknown. Recently, we observed that activated p38 immunohistostaining was increased in scrapie-infected mice. In many neurodegenerative diseases, activation of the p38 pathway and of the immediate-early gene termed c-Fos appears to be required for the initiation of apoptosis. There are similarities in histopathological changes seen in scrapie-infected mice and in an uninfected senescence-accelerated mouse strain (SAMP8). This led us to investigate c-Fos protein levels in the brains of both uninfected and scrapie-infected SAMP8, SAMR1, AKR and C57BL mice using immunohistochemical methods. The SAMR1 strain served as a control in that it is a mouse strain that does not show accelerated ageing, but has a background that is similar to the SAMP8 strain. AKR was used because it is one of the progenitor strains of both SAM strains and, finally, C57BL is a completely unrelated strain. The results showed a low basal c-Fos expression in controls and a marked increase in c-Fos staining in scrapie-infected mice. In scrapie-positive mice, c-Fos immunoreactivity was observed in neurones in the cortex, hippocampus, thalamus, hypothalamus, medulla, midbrain, brainstem, paraterminal body, internal capsule and cerebellar Purkinje cells. Immunoreactivity of c-Fos was also observed in astrocytes in many brain areas of scrapie-infected mice, particularly in the hippocampus and cortex. Our results show that normal mouse brain (NMB)-injected AKR and SAMP8 mice had more c-Fos production than NMB-injected SAMR1 or C57BL mice; scrapie-infection induces significant increases in c-Fos immunoreactivity in all four mouse strains. Our study suggests that the increase in c-Fos levels may play a role in the neuronal apoptosis observed in scrapie-infected mice.

Aging↗
PubMed2002

Structure and ultrastructure of the celiac-mesenteric ganglion complex in the domestic dog (Canis familiaris).

A number of neurons of the autonomic nervous system are situated in the ganglia and can be systematically divided into pre-vertebrals, paravertebrals, intramural and para-viscerals. The celiac-mesenteric ganglion, an important pre-vertebral ganglion, is located together with the abdominal aorta and links the central nervous system to the peripheral system, participating in the coordination of peripheral reflexes and principally innervating the stomach, intestines, accessory glands (liver and pancreas). In addition, the celiac-mesenteric ganglion also contributes to the innervation of the spleen and has a role in gastrointestinal motility control. This study examined the structural and ultrastructural aspects of 40 celiac-mesenteric ganglia from domestic dogs. For light microscopy ganglia were included in paraplast and stained with haematoxylin-eosin, picrosirius, toluidine blue, Calleja's and Masson's trichrome. For examination by electron microscopy, the ganglia were submitted to cryofracture, enzyme digestion, hydrolysis and fixed in 5% glutaraldehyde in 0.1 M phosphate buffer (pH 7.4). The celiac-mesenteric ganglion was observed as a ganglionic complex composed of various ganglionic units separated by types I and III collagen fibres, predominantly unmyelinated nerve fibres and continuous capillaries. This complex is surrounded by a double-layer capsule (internal and external). The principal ganglion cells had eccentric nuclei with two nucleoli, the nucleolemma was double and presented nuclear pores. In the cytoplasm there were vesicles of the Golgi apparatus, electron-dense vacuoles, mitochondrias, smooth and granulated endoplasmic reticulum and free ribosomes. In conclusion, this ganglionic complex, in contrast to similar structures in the enteric nervous system, presents separate ganglionic units in a systematic arrangement related to the extrinsic and specific innervation of the target organs.

Animals↗
PubMed1998

Transient features of the thalamic reticular nucleus in the human foetal brain.

The architectonic organization and neuronal types of the human foetal reticular nucleus (RN)--with special reference to transient characteristics--have been investigated using antisera against calretinin, parvalbumin and neurofilament epitopes of somata and dendrites (SMI 311). The RN consists of four subdivisions (clearly distinguishable in the 6/7th gestational month): The main portion appears as a prominent structure on account of its extension and high packing density of neurons which coexpress calretinin and parvalbumin. These two calcium-binding proteins are also expressed by the perireticular nucleus forming a conspicuous grey within the internal capsule. Perireticular cells form clusters which are in continuity with the main portion, globus pallidus, ganglionic eminence and pregeniculate nucleus. In double-labellings, a medial subnucleus stands out distinctly as it only expresses calretinin. SMI 311-immunopreparations show neurons revealing a high degree of diversification and elaborated dendritic trees. Several transient characteristics become obvious: the perireticular nucleus, not visible in the adult, represents a distinct entity in the human foetal brain. The main portion and the pregeniculate nucleus appearing as prominent greys are dramatically reduced in size later on. The percentage of RN-neurons expressing calretinin, the diversity of neuronal types and elaborated dendritic trees are reduced. The transient features can be correlated with the RN's putative functional roles in development: early RN-afferents to the dorsal thalamus may represent pioneer fibres providing guiding cues for outgrowing axons from or into the thalamus. Moreover, the RN may serve as an intermediate target for growing axons which are sorted and directed towards different final targets.

Antibodies, Monoclonal↗
PubMed2000

Programmed cell death in the developing human telencephalon.

Programmed cell death (PCD) in the form of apoptosis is recognized as one of the central events in the development of the central nervous system. To study the time of onset, extent and distribution of PCD in the human telencephalon, embryos and fetuses from 4.5 to 27 gestational weeks (g.w.) were examined using the TUNEL (TdT-mediated dUTP-biotin nick-end labelling) in situ method. At 4.5 g.w. sparse TUNEL(+) nuclei were observed in the ventricular zone of the neural tube. With the formation of the cortical plate at 7-8 g.w. , TUNEL(+) nuclei were seen in all developmental layers of the cortical anlage, as well as in the subcortical regions such as the ganglionic eminence and the internal capsule. The proliferative zones (the ventricular zone, the subventricular zone and the ganglionic eminence) contained the majority of all apoptotic nuclei observed in each specimen. However, the apoptotic index was highest in the subplate zone and in layer I. Double-labelling experiments suggested that neuronal precursors were the main population of cells undergoing PCD in the first trimester of gestation, whereas glial cells probably start dying around midgestation. The onset of labelling of microglial cells and apoptotic nuclei were synchronous, indicating the involvement of microglia in PCD. In conclusion, two distinct types of PCD were observed during human telencephalic development: embryonic apoptosis, which was synchronous with proliferation and migration of neuronal cells and probably not related to establishment of neuronal circuitry, and fetal apoptosis, which coincided with differentiation and synaptogenesis, and therefore may be related to the development of axonal-target connectivity.

Apoptosis↗
PubMed2000

Symptomatic paroxysmal hemidystonia due to a demyelinating subthalamic lesion.

We present a case of paroxysmal hemidystonia in a patient with an isolated demyelinating lesion in the subthalamic region, involving the posterior arm of the internal capsule and extending to the subthalamic nucleus and mesencephalon, possibly due to multiple sclerosis. Compared with similar reports in the literature, in our case there was a paucity of lesions, permitting a more direct clinico-anatomical correlation. The role of the subthalamic region and basal ganglia circuitry in the genesis of symptomatic dystonia is discussed.

Adult↗
PubMed2003

Subacute rhombencephalitis optica responsive to intravenous immunoglobulins.

A 53-year-old man presented with optic neuritis, followed within 10 weeks by a subacute progression of weakness, ataxia, and multiple cranial nerve palsies. Cranial magnetic resonance imaging demonstrated multiple T2-hyperintense lesions extending from the ponto-medullary junction to the thalamus and internal capsule. Cerebrospinal fluid analysis showed lymphocytic pleocytosis with elevated protein content. A brain biopsy revealed inflammatory changes. After a month long period of inexorable worsening, the patient was treated with intravenous immunoglobulins (2 g/kg). He responded to treatment, and recovered over the subsequent 3 months. The patient's response to treatment suggests that intravenous immunoglobulins should be considered in patients with inflammatory brain disorders.

Encephalitis↗
PubMedDate not supplied

Headache secondary to deep brain implantation.

This article examines the headaches that can develop with deep brain stimulation. We identified 15 (23.4%) of 64 patients who developed chronic headaches following implantation of deep brain stimulation electrodes for relief of chronic pain syndromes. Electrodes were implanted in the periaqueductal gray, sensory thalamus, and internal capsule. None of these 15 patients reported similar headaches prior to the implantation. Although 5 patients were intermittent headache sufferers prior to implantation, they reported post-implantation headaches to be completely different in nature. Our experience suggests that headache syndromes may arise due to disturbance of serotonergic neurotransmission within deep brain structures.

Adult↗
PubMed2002

Cajal-Retzius and subplate neurons: their role in cortical development.

Cajal-Retzius (C-R) neurons and their processes form a synaptic network in the marginal zone of the early telencephalon prior to the arrival of the first wave of radial migration of neuroblasts from the subventricular zone. Their origin is not yet proved but may be either the medial ganglionic eminence or the mesencephalic neuromere. These bipolar or multipolar neurons populate the molecular layers of both the fetus and the adult, though sparse in the adult. Their thick axon emits collaterals that make synaptic contact with pyramidal neurons initially in layer 6 and later within all layers. C-R neurons produce GABA, possibly ACh, several calcium-binding proteins (e.g. calmodulin; parvalbumin; possibly calretinin), several neuropeptides and are rich in ribosomes. Subplate neurons, beneath the cortical plate, emit pioneer axons in the incipient formation of the internal capsule and also commissural fibres of the early hippocampus. C-R cells express products of the genes reelin, LIS1 and DS-CAM, that mediate radial neuroblast migration and lamination of the cortical plate and are important in the pathogenesis of lissencephaly. In addition to forming the first intrinsic synaptic circuits of the cortical plate and its first afferent and efferent connections with subcortical structures, they may play additional roles in the formation of ocular dominance columns, in regulating neuronogenesis and in cortical repair. They do not later disappear by apoptosis as we previously thought, but their functional role in the mature brain is unknown.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2001

Histological observations on the brains of symptomless 7-year-old cattle.

The histological changes in the brains of 506 clinically normal 7-year-old cattle, which were part of a cohort study on maternal transmission of bovine spongiform encephalopathy, are described. Vacuolation of the white matter, of unknown aetiology, located particularly in the substantia nigra, was a frequent finding. Vacuolated neurons were commonly observed in the red nucleus (64.3% of the animals) and in the habenular nucleus (50.1%). Spheroids were found in 10.8% of the brains, most frequently in the vestibular nuclei. Cellular inflammatory infiltrates in association with blood vessels occurred in 30% of the animals at various locations in the brain; their aetiology remains uncertain, but they may have reflected subclinical or latent infections. Mineralization of the wall of blood vessels, with proliferation of the intima, was observed frequently in vessels of the internal capsule and was probably associated with ageing. The description of histological findings in the brain of symptomless adult cattle in the present study provides a useful background for diagnostic bovine neuropathology.

Animals↗
PubMed2002

Effects of intravenous injection of Clostridium perfringens type D epsilon toxin in calves.

In cattle, a neurological lesion similar to that produced in sheep and goats by Clostridium perfringens type D enterotoxaemia has been reported. However, no causal relationship has been established between this disease and the lesion in cattle. The effects of single and multiple intravenous injections of epsilon toxin in three calves aged 6 months were studied. A further calf was inoculated intravenously with saline solution and used as a control. Epsilon toxin invariably produced neurological signs within 2-60 min of the end of the injection process. Clinical signs consisted of loss of consciousness, recumbency, convulsions, paddling, opisthotonus, hyperaesthesia and dyspnoea. Gross changes consisted of severe acute pulmonary oedema, which was particularly marked in the interlobular septa. The histological lesions consisted of intra-alveolar and interstitial oedema of the lung and variable degrees of perivascular proteinaceous oedema in the internal capsule, thalamus and cerebellar white matter. No clinical or post-mortem changes were observed in the control calf. These results show that calves are susceptible to the intravenous injection of epsilon toxin, and that they can show at least some of the histological lesions produced in sheep and goats by this toxin.

Acute Disease↗
PubMed2000

Brain lesion size and location: effects on motor recovery and functional outcome in stroke patients.

OBJECTIVE: To investigate effects of brain lesion profiles that combined sizes and locations on motor recovery and functional outcome after stroke in hemiplegic patients. DESIGN: Delimiting sizes (a threshold lesion size) of 5 primary locations were identified to establish brain lesion profiles based on magnetic resonance imaging findings 1 month after stroke. Motor and functional outcome were correlated with brain lesion profiles and other brain lesion factors to identify the most dominant factor. SETTING: Medical center, rehabilitation department. PARTICIPANTS: Fifty-five hemiplegic patients. MAIN OUTCOME MEASURES: Brunnström's stages and Functional Independence Measure (FIM) scores were assessed 1 and 6 months after stroke. RESULTS: With delimiting sizes for the cortical, corona radiata, internal capsule, putaminal, and thalamic regions set at 75, 4, .75, 22, and 12cm3, respectively, brain lesion profiles play a dominant role in determining final Brunnström's stages (Spearman's rho = .861, p < .01) and FIM score (Spearman's rho = .571, p < .01). Brunnström's and FIM scores had no or only weak negative relationship with either absolute or relative lesion size. CONCLUSIONS: These findings may suggest that motor and functional outcomes after stroke correlate with brain lesion profiles (a combination of delimiting sizes and primary locations) more than with absolute or relative lesion sizes only. Delimiting sizes in determining final outcomes varied markedly according to the primary lesion locations.

Aged↗