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Visualizing the evolution of abnormal metabolic networks in the brain using PET.

By applying novel statistical methods and visualization techniques to PET data obtained from combined groups of patients and normals, we are able to illustrate topographic covariance profiles unique to neurodegenerative disorders such as Parkinson's Disease at various stages of progression. Each profile represents a neuroanatomical network of metabolically covarying regions. The expression of the profile in each patient is characterized by a subject score which can correlate with independent clinical disease severity measures. To visualize these profiles, a semi-automatic routine is used (3D) animation of the metabolic topography as it evolves from initial to final stages of the disease.

Adult↗

Identification with a monoclonal antibody of a phylogenetically conserved brain-specific determinant on a 130,000 molecular weight glycoprotein of human brain.

Human brain glycoproteins depleted of Thy-1 antigen were used to immunise Balb/c mice for monoclonal antibody production. The F3-87-8 antibody described in this paper interacts with a determinant present in large amounts on all human brain subregions studied (cerebral cortical grey matter, white matter, caudate, thalamus, dentate nucleus, putamen, cerebellar cortex) but absent from all other tissues examined (liver, heart, kidney, spleen, thymus, lymph node, erythrocyte, adrenal gland, and peripheral nerve). The determinant is conserved in mammalian evolution, as the brains of the rat and dog have amounts equal to that found in human brain. Balb/c mouse brain has approximately one-third as much antigen activity as these other mammalian brains, whereas brains of the frog and chicken have no detectable antigenic activity. Developmental studies showed that 16-week human foetal brain and neonatal dog brain had little or no antigen activity, indicating a dramatic increase in the amount of the determinant with brain maturation. Biochemical studies showed that the F3-87-8-bearing molecule was a major sialoglycoprotein of human brain with an apparent molecular weight of 130,000. It was shown by immunofluorescence to be particularly localised in what appeared to be fibre tracts in the thalamus and basal ganglia, and in the dentate nucleus, although all regions including grey matter were stained.

Animals↗

Cyclic vomiting syndrome: evolution in our understanding of a brain-gut disorder.

Cyclic vomiting syndrome (CVS) remains a mysterious disorder despite our increasing knowledge since its classic description by Gee in 1882. Its hallmark feature of recurrent, explosive bouts of vomiting punctuating periods of normal health causes substantial medical morbidity (50% of patients require intravenous therapy), as well as significant time lost from school (20 school absences per year) and work. Limited epidemiologic data indicate that CVS may occur more commonly than previously thought, affecting as many as 1.9% of school-aged children. Besides the relentless vomiting, the child usually has pallor (87%), lethargy (91%), anorexia (74%), nausea (72%), and abdominal pain (80%). There is evidence of clinical and physiologic overlap among CVS, abdominal migraine, and migraine headaches. We propose revised criteria for abdominal migraine that include pain as the predominant and consistent symptom, lack of abnormal screening tests, and in retrospect, either subsequent development of migraines or positive response to antimigraine medication. Besides migraines, other etiologic possibilities include mitochondrial DNA mutations, ion channelopathies, excessive hypothalamic-pituitary-adrenal axis activation, and heightened autonomic reactivity. The differential diagnosis includes idiopathic CVS (88%); gastrointestinal disorders (7%), including serious surgical disorders (e.g., malrotation); and extraintestinal disorders (5%), including serious surgical (brain stem neoplasm) and metabolic disorders (e.g., fatty acid oxidation disorder). Within the idiopathic group, there may be migraine, Sato's neuroendocrine, mitochondrial, and other subgroups. Treatment includes avoidance of triggers, prophylactic medication, supportive care, abortive medication, and family support. In the future, investigation into mitochondrial DNA mutations, ion channel defects, corticotropin-releasing factor, and serotonin and tachykinin receptor physiology and pharmacology may help discover the etiology and pathogenesis of this disorder.

Antiemetics↗

The copper-peroxide-silver method: a highly sensitive procedure for the demonstration of Alzheimer's disease lesions and for signal intensification in immunocytochemistry.

Ammoniacal silver solutions give striking impregnation of Alzheimer's disease (AD) lesions if sections are pretreated with copper sulfate and hydrogen peroxide. In contrast to most silver impregnation methods, no staining of normal neurites is obtained, and senile plaques (SPs), neurofibrillary tangles (NFTs), and neuropil threads (NTs) are strongly stained in black against a clear background. A sodium acetate wash interposed between the copper sulfate and hydrogen peroxide resulted in suppression of the staining of amyloid lesions. This variant of the basic procedure (CPS-II method), maintains the capacity of the latter (CPS-I method) to strongly impregnate NFTs and NTs. In addition, it clearly delineates the dystrophic neurites of SPs obscured by the strong argyrophilia of the amyloid deposits seen in CPS-I stains. NTs are strongly impregnated with both CPS-I and CPS-II methods and are unmasked from normal neurites, which remain unstained. The staining can be abolished by pretreatment with formic acid and erased with a brief wash in sulfochromic acid. Destained sections can be restained with either method or with immunoperoxidase procedures. CPS staining of previously immunostained tissues produces marked intensification of the diaminobenzidine reaction product. In AD brains, the immunostaining is markedly enhanced and selective when the silver procedure is preceded by formic acid treatment. The selectivity and high sensitivity of the procedure may be useful as a diagnostic tool and of value to study the biogenesis and natural evolution of the brain lesions of AD.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimer Disease↗

Time course of lesion development in patients with acute brain stem infarction and correlation with NIHSS score.

BACKGROUND AND PURPOSE: diffusion weighted magnetic resonance imaging (MRI) is highly sensitive in detecting acute supratentorial cerebral ischemia and Diffusion Weighted Imaging (DWI) lesion size has been shown to correlate strongly with the neurologic deficit in middle cerebral artery territory stroke. However, data concerning infratentorial strokes are rare. We examined the size and evolution of acute brain stem ischemic lesions and their relationship to neurological outcome. METHODS: brain stem infarctions of 11 patients were analyzed. We performed DWI in all patients and in 7/11 patients within 24 h, T2W sequences within the first 2 weeks (10/11 patients) and follow-up MRI (MR2) within 3-9 months (median 4.8 months) later (12/12 patients). Lesion volumes were compared with early and follow-up neurologic deficit as determined by National Institutes of Health Stroke Scale (NIHSS) score. RESULTS: the relative infarct volumes--with MR2 lesion size set to 100%--decreased over the time (P<0.02) with a mean shrinking factor of 3.3 between DWI (MR0) and the follow-up MRT (P<0.02), and 1.6 between early T2W (MR1) and MR2 (P<0.04). The mean DWI volume size (MR0) was larger than the early T2W (P<0.02). Although neurological outcome was good in all patients (mean NIHSS score of 1.3 at follow-up), early NIHSS and follow-up NIHSS scores were strongly correlated (r=0.9, P<0.00). NIHSS score at follow-up was highly correlated with lesion size of DWI (MR0; r=0.71, P<0.04) and T2W of MR1 (r=0.86, P<0.001). CONCLUSIONS: in this study, we saw a shrinking of the brain stem infarct volume according to clinical improvement of patients. Great extension of restricted diffusion in the acute stage does not necessarily implicate a large resulting infarction or a bad clinical outcome.

Brain Stem Infarctions↗

[Early evoked auditory potentials in transient ischemic attacks of the posterior circle of Willis].

The authors studies through the evoked potentials of the brain stem a group of patients affected from T.I.A. of the vertebro-basilar circulation. From the remarks of cases this examination results significant in 66%. The more characteristic remarks is the increase of absolute latency of V wave. It is also possible to follow contemporary the evolution of auditive brain pathways disease and clinical features in repeating the test.

Adult↗

Genes, brains and mammalian social bonds.

Recent studies of monogamous species have revealed the role of the neuropeptides oxytocin and vasopressin in activating reward mechanisms of the brain that are involved in establishing partner recognition and selective 'bonding'. The evolutionary history of these findings resides, at a mechanistic level, in the reciprocal bonding between mother and infant that is common to all mammals. However, in Old World primates, where mother and infant alone would not survive, living in large social groups brings extended family relationships and provides for alloparenting. This has required the emancipation of parenting behaviour from the constraints of hormonal state and the evolution of large brains for decision making that was previously restricted and determined by hormonal state. How this has been achieved, what conserved mechanisms underpin social bonding, and what genetic and mechanistic changes have occurred in the evolution of social bonds are the issues addressed here.

Journal Article↗

Temporal evolution and spatial distribution of the diffusion constant of water in rat brain after transient middle cerebral artery occlusion.

The regional distribution and temporal evolution of the diffusion coefficient (Dw) of water in rat brain was measured during and after transient middle cerebral artery (MCA) occlusion. Male Wistar rats (n = 14) were subjected to 2 h of middle cerebral artery occlusion, induced by intracarotid insertion of a filament. Diffusion (n = 14) and perfusion (n = 7) weighted magnetic resonance imaging were performed before, and at various time points after MCA occlusion, ranging from 30 min up to 7 days. Our data demonstrate that the temporal profiles of Dw differ between the severely and the least damaged regions of tissue. In the core of the lesion, where the tissue evolved to necrosis, Dw declined significantly (P < 0.001) within 0.5 h after onset of ischemia, and remained depressed until 24 h after withdrawal of the suture. However, no statistically significant decline in Dw was found in the perifocal regions containing morphologically intact cells. Perfusion MRI qualitatively exhibited a hypoperfusion and reperfusion during, and after 2 h MCA occlusion, respectively. A significant (r > or = 0.71, P < 0.01) correlation was found between delta Dw (the difference in Dw between the ipsilateral ischemic and homologous contralateral control regions) obtained immediately before withdrawal of the suture (2 h of ischemia) and at specific early time points after withdrawal of the suture, and the degree of ischemic cell damage. No significant (P > 0.01) correlation was detected at an early time points of ischemia or at other time points after withdrawal of the suture.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ischemic cerebral edema in primates: effects of acetazolamide, phenytoin, sorbitol, dexamethasone, and methylprednisolone on brain water and electrolytes.

Brain edema was induced in primates (Macaca mulatta) after regional cerebral ischemia produced by selective embolization of the internal carotid artery bifurcation. Details of the alterations in the distribution of water and electrolytes in the brain during the evolution of ischemic cerebral edema have been described elsewhere. The effects of five theoretically useful pharmacological agents were studied. Acetazolamide failed to improve ischemic edema and, rather, increased mortality. Phenytoin definitely prevented both edema and infarction in only the cerebral cortex. Sorbitol was effective to induce dehydration of the affected cortex and the normal brain tissue, with obvious reduction of the brain bulk. High dose steroids showed an ability to modify edema in the cortex, putamen, and white matter. However, animals treated with methylprednisolone rather than dexamethasone showed a better neurological recovery and smaller infarcts.

Acetazolamide↗

Anoxia tolerant brains.

While medical science has struggled to find ways to counteract anoxic brain damage with limited success, evolution has repeatedly solved this problem. The best-studied examples of anoxia-tolerant vertebrates are the crucian carp and some North American Freshwater turtles. These can survive anoxia for days to months, depending of temperature. Both animals successfully fight any major fall in brain ATP levels, but the strategies they use to accomplish this are quite divergent. The anoxic turtle suppresses brain activity to such a degree that it becomes virtually comatose. The underlying mechanisms involve closing down ion conductances and releasing GABA and adenosine. By contrast, the crucian carp remains active in anoxia, although it suppresses selected brain functions, and avoids lactate self-poisoning by producing an exotic anaerobic end-product. These animals provide unique models for studying anoxic survival mechanisms both on a molecular and physiological level.

Adaptation, Physiological↗

[Evolution and function of sleep].

This paper presents a brief historical review of the beginning of scientific studies on sleep research and evaluation of the electrophysiological basics. Subsequently, hypotheses are presented and discussed on phylogenesis and function of NONREM- and REM-sleep as well as aspects of the regulation of energy conservation and temperature. Sleep may have first evolved out of rest/activity cycles. Later on, with the evolution of complex brains, sleep may also assume importance in development and maintenance of these structures. Hence, special emphasis is placed on the influence of NONREM and REM sleep on the reorganisation of neuronal networks.

Animals↗

Early neurophysiological assessment after insult to the central nervous system.

Cerebral insult is a generic term which includes many causes of altered cerebral function. Neurophysiological investigations, closely integrated with clinical and metabolic studies, should begin at an early stage after any such insult (namely in the first few hours) to provide information on the type, severity and evolution of latered brain function. The present contribution is based on prospective studies on 200 children with closed head injuries and 500 children who had been resuscitated following cardiocirculatory or respiratory arrest. In addition to electroencephalography, other neurophysiological investigations may be carried out whenever necessary including electroretinography, evoked potential studies and polyelectromyography at the patient's bedside, whether or not in the intensive care situation. The rapid evolution of metabolic events and of both clinical and neurophysiological features characterizes the acute initial phase, in marked contrast to the more static features of long term sequelae to a cerebral insult. Experience over the past 25 yr has shown that no rule is applicable to every case because of the diversity of individual circumstances. However, a well planned early neurophysiological assessment after insult to the central nervous system has given reliable prognostic criteria for the subsequent management of each patient and for the evaluation of any complications during the first few weeks of treatment.

Brain↗

History of brain and epidural metastases from breast cancer in relation with the disease evolution outside the central nervous system.

We reviewed 89 breast cancer patients with brain or epidural metastases in order to see whether a parallelism could be found between disease evolution inside and outside the central nervous system. One-fifth of the patients with brain metastases did not have any other site of relapse before neurological complication. Among the 38 patients who developed brain metastases and had a prior history of relapse outside the brain, 12 had control of constant extracranial sites while disease was progressing at these sites in 26 of them. In the epidural metastases group, all patients but 4 had progressive disease elsewhere when neurological complication appeared.

Adult↗

[The brain of the Agnatha].

The brain of the Agnatha, especially of the hagfish, is discussed from the viewpoint of the telencephalon and the olfactory, visual, trigeminal, and vestibulolateral sensory systems. Myxiniformes and Petromyzontiformes, which were an independent group in the Ordovician, are thought to represent some parallels of ancestral vertebrate brains. It is interesting to study the brain of the Agnatha to investigate the process of the evolution of the vertebrate brain. In comparison with the lamprey, the hagfish has subcutaneous eyes under an unpigmented patch of skin, 4 paired tentacles at the rostral tip of the head, one semicircular canal on each side, a regressed ventricular system, a "primordium hippocampi" of unresolved homology in the telencephalon, no pineal body, fusion of the habenula of both sides, a tectum opticum with unclear laminations, no macroscopical cerebellum, and optic decussation within the hypothalamus. The arrangements of the trigeminal subnuclei of the descending tract are different from each other, unlike those of other gnathosomata. In the hagfish, the distribution of fibers carrying input of the vestibulum and lateral line system within the area vestibulo-lateralis differs from that of the lamprey, which resembles the teleosts and cartilaginous fish in this respect. These differences may be caused by an independent origin within the Agnatha. The basic organization of the brain of the Agnatha, such as the prosencephalon, mesencephalon, and rhombencephalon are common to the gnathostomata, although some variations in development are included in the sensory centers and higher centers of information processing. The sensory neurons within the brain are found in the medulla oblongata in the Agnatha, whereas in the gnathostomata the mesencephalic nucleus of the trigeminal nerve has been formed in connection with the development of the mandibula.

Animals↗