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At least 91 records · Page 5Linked to original sources
PubMed2005

N-methyl-D-aspartate receptor subtypes: multiple roles in excitotoxicity and neurological disease.

N-methyl-D-aspartate (NMDA) receptors are the major mediator of excitotoxicity. Although physiological activation of the NMDA receptor is necessary for cell survival, overactivation is a signal for cell death. Several pathways are activated through NMDA receptor stimulation, most of which can contribute to excitotoxicity. These include events leading to mitochondrial dysfunction, activation of calcium-dependent enzymes, and activation of mitogen-activated protein kinase pathways. Understanding the role of these mechanisms is important in developing agents that block excitotoxicity without inhibiting functions necessary for survival. NMDA receptor subtypes may be responsible for mediating separate pathways, and subtype-specific inhibition has shown promising results in some neurological models. This review examines the roles of NMDA receptor subtypes in excitotoxicity and neurological disorders.

Animals↗
PubMed2006

A neurolinguistic model of grammatical construction processing.

One of the functions of everyday human language is to communicate meaning. Thus, when one hears or reads the sentence, "John gave a book to Mary," some aspect of an event concerning the transfer of possession of a book from John to Mary is (hopefully) transmitted. One theoretical approach to language referred to as construction grammar emphasizes this link between sentence structure and meaning in the form of grammatical constructions. The objective of the current research is to (1) outline a functional description of grammatical construction processing based on principles of psycholinguistics, (2) develop a model of how these functions can be implemented in human neurophysiology, and then (3) demonstrate the feasibility of the resulting model in processing languages of typologically diverse natures, that is, English, French, and Japanese. In this context, particular interest will be directed toward the processing of novel compositional structure of relative phrases. The simulation results are discussed in the context of recent neurophysiological studies of language processing.

Brain↗
PubMed1999

The contribution of Hughlings Jackson to an understanding of dissociation.

The author provides a preliminary framework for a systematic and dynamic understanding of dissociation through a consideration of the theories of Hughlings Jackson. Jackson's ideas are briefly reviewed. He saw the proper scientific investigation of mental illness as an experimental investigation of mind. Accordingly, his argument begins with this fundamental concept. His views of the brain-mind relationship and of mind, or self, resemble modern conceptions. He viewed the self as double and focused on those disruptions of the self system which he called the "dreamy state." This state involves an "uncoupling" of normal consciousness, resulting in the loss of the most recently developed forms of memory and of the stream of consciousness. Dissociation is seen here as analogous to the dreamy state. Jacksonian theory predicts the main features of dissociation, i.e., constriction of consciousness, a particular form of amnesia, disaggregation of perceptual phenomena, depersonalization, derealization, and hallucinosis. It leads to the view that dissociation can be seen, in essence, as an uncoupling of consciousness.

Biological Evolution↗
PubMed1989

A regression model for carpal tunnel syndrome.

The purpose of this study was to determine whether a logistic regression model for the diagnosis of carpal tunnel syndrome (CTS) could be developed. Forty-eight variables were initially identified, for the 28 CTS and 34 non-CTS subjects, including 28 measures of nerve function, 6 anatomical measurements, 8 variables relating to disease symptoms, and 6 variables relating to physical attributes. An a priori clustering procedure was used to establish groups for the principal components analyses. The first principal component of each cluster was then used in a backward, stepwise logistic regression analysis. The best combination of candidate variables, as identified by the regression equation, was Raynaud's symptoms and median nerve motor function. The results of this study indicate that a model for CTS can be generated from a set of variables and that a linear combination of variables representing nerve function is closely associated with conduction decrements resulting from CTS.

Carpal Tunnel Syndrome↗
PubMed1993

Mixture estimation and the neurophysiological quantal hypothesis.

Quantal release models provide a mechanistic description of the process by which neurotransmitter is released from the nerve cell. The usual such model assumes that the quantity of transmitter released after nerve depolarization follows a finite mixture distribution with an unknown number of components, and with constraints on component means and variances. General procedures for estimating the dimension of a finite mixture model are discussed, and applied to the analysis of a quantal release data set.

Action Potentials↗
PubMed1989

[Experimental studies on pharmacologic protection of the brain against focal ischemia. 2. Effects of KB-2796 and nicardipine on focal brain ischemia in rats].

It has been proposed that calcium overload triggers neuronal cell damage in the acute stage of cerebral ischemia. In this study, the effects of calcium antagonists, KB-2796 and nicardipine, on neurologic deficits and size of the infarction were studied in the rat middle cerebral artery (MCA) occlusion model. Neurologic deficits were evaluated from 1 to 24 hours after occlusion of the MCA, using a grading system of Bederson et al. At 24 hours post-occlusion, the brain was removed, sliced coronally, and stained with triphenyltetrazolium chloride. Size of the infarction was measured by computerized image analysis system. KB-2796 (10 mg/kg) or nicardipine (1 mg/kg) was intraperitoneally administered immediately after occlusion of the MCA. In the KB-2796-treated group, the neurologic deficits were much improved and the size of infarction was significantly smaller, but in the nicardipine-treated group improvement was modest and did not reach the level of statistical significance. The neurologic improvement was observed in the group where KB-2796 was given at 3 hours post-occlusion but the size of infarction was unchanged. The results in the present study seem to indicate that the calcium antagonists could improve focal cerebral ischemia when administered in early stage of ischemia, and that such effect is more significant with KB-2796 probably because of its higher selectivity to the cerebral vessels.

Animals↗
PubMed1999

Progression of rheumatoid arthritis of the cervical spine: radiographic and clinical evaluation.

Cross-sectional and longitudinal studies were conducted to observe progression of rheumatoid arthritis in the cervical spine. Two hundred and ninety-seven patients were enrolled in the cross-sectional study. Both upper and lower cervical spine involvement increased with disease duration. The relationship between atlanto-axial motion and the development of subaxial subluxation was inconclusive. Eighty-seven patients were enrolled in the longitudinal study and were followed for at least 5 years. In about half of these patients, rheumatoid changes started from the upper cervical spine, with rheumatoid changes beginning from the lower cervical spine in about 8% of patients. Neurological deficits were correlated with radiographic changes but neck pain did not correlate with radiographic changes. As to the upper cervical spine, the parameter most influencing neurological deficits was found to be the minimum value of the atlanto-axial angle in flexion, by multivariate analysis using a multiple logistic model. Neurological deficits were seen in more than half the patients when the atlanto-axial angle in flexion was 5 degrees or less.

Adult↗
PubMed2004

Outcomes in patients admitted for rehabilitation with spinal neurological lesions following intervertebral disc herniation.

BACKGROUND: Little information is available about the survival, neurological recovery, and length of stay in hospital for rehabilitation (LOS) of patients with spinal neurological deficit following disc herniation (DH). STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To report on outcomes and factors affecting these. SETTING: The Spinal Research Laboratory, Loewenstein Rehabilitation Hospital, Israel. SUBJECTS: A total of 158 patients with DH spinal neurological lesions (DHSNL). METHOD: Data were collected retrospectively. Survival was assessed using the Kaplan-Meier method; relative mortality risk by the Cox proportional hazard model. Neurological recovery was evaluated by calculating the change in Frankel grades, and factors that affect it were assessed by logistic regression. LOS associations were analyzed with ANOVA. RESULTS: The median age at lesion onset was 48 years, and the median survival 29 years. Age and gender had a significant effect on survival, but not so lesion severity, level, or decade of onset. Of the 69 patients who had Frankel grades A, B, or C on admission, 72% achieved useful recovery to grades D or E. The severity and level of the spinal neurological lesion (SNL) had a significant effect on recovery. The mean LOS was 87 days; it was significantly affected by lesion severity and level and by the decade of admission to rehabilitation, and decreased with time. CONCLUSIONS: Patients with DHSNL who were admitted for rehabilitation have favorable survival and recovery rates compared with previously studied patients with other types of SNL. Their LOS is probably a function of medical requirements, but is decreasing with time.

Age Factors↗
PubMed1995

Models of delayed recovery.

After a biologic insult has impaired function of the developing central nervous system, recovery may not become apparent for years. Probability models adopted from the carcinogenesis, developmental neurobiology, learning decay, and stochastic process literatures are presented so that assumptions about apparent delays in the recovery process can be tested with data from longitudinal studies after a temporally circumscribed adverse event/exposure. This process of evaluating multiple models is exemplified with one data set. Nonlinear models of recovery are important because some children with early deficits first show improvement months to years later.

Brain↗
PubMedDate not supplied

The basis of anisotropic water diffusion in the nervous system - a technical review.

Anisotropic water diffusion in neural fibres such as nerve, white matter in spinal cord, or white matter in brain forms the basis for the utilization of diffusion tensor imaging (DTI) to track fibre pathways. The fact that water diffusion is sensitive to the underlying tissue microstructure provides a unique method of assessing the orientation and integrity of these neural fibres, which may be useful in assessing a number of neurological disorders. The purpose of this review is to characterize the relationship of nuclear magnetic resonance measurements of water diffusion and its anisotropy (i.e. directional dependence) with the underlying microstructure of neural fibres. The emphasis of the review will be on model neurological systems both in vitro and in vivo. A systematic discussion of the possible sources of anisotropy and their evaluation will be presented followed by an overview of various studies of restricted diffusion and compartmentation as they relate to anisotropy. Pertinent pathological models, developmental studies and theoretical analyses provide further insight into the basis of anisotropic diffusion and its potential utility in the nervous system.

Anisotropy↗
PubMed2005

Outcomes in patients admitted for rehabilitation with spinal cord or cauda equina lesions following degenerative spinal stenosis.

PURPOSE: To evaluate outcome measures and the factors affecting them in patients treated between 1,962 and 2,000 at Loewenstein Rehabilitation Hospital, Israel. METHOD: This retrospective cohort study included 262 patients with spinal neurological lesions (spinal cord or cauda equina lesions) following degenerative spinal stenosis. Data were collected retrospectively. Survival was assessed using the Kaplan-Meier method and the relative mortality risk by the Cox model. Neurological recovery was evaluated by the change in Frankel grades, and factors that affect it were assessed by logistic regression. Associations of length of stay in rehabilitation were analyzed with ANOVA. RESULTS: Median age at lesion onset was 61 years and median survival 17.6 years. Age at spinal neurological lesion onset was found to be the only factor with a significant effect on survival. Of the 148 patients who had Frankel grades A, B, or C on admission, 58% achieved recovery to grades D and E. Frankel grade at admission, age, and spinal neurological level had a significant effect on recovery. The mean length of stay was 99.7 days, and only Frankel grade had a significant effect on length of stay. CONCLUSIONS: Patients with spinal stenosis and disabling spinal neurological lesions can achieve significant neurological recovery and survive for many years. They require adequate care in a specialist rehabilitation system.

Cauda Equina↗
PubMed2005

Outcomes in patients admitted for rehabilitation with spinal cord or cauda equina lesions following degenerative spinal stenosis.

PURPOSE: To evaluate outcome measures and the factors affecting them in patients treated between 1962 and 2000 at Loewenstein Rehabilitation Hospital, Israel. METHOD: This retrospective cohort study included 262 patients with spinal neurological lesions (spinal cord or cauda equina lesions) following degenerative spinal stenosis. Data were collected retrospectively. Survival was assessed using the Kaplan-Meier method and the relative mortality risk by the Cox model. Neurological recovery was evaluated by the change in Frankel grades, and factors that affect it were assessed by logistic regression. Associations of length of stay in rehabilitation were analyzed with ANOVA. RESULTS: Median age at lesion onset was 61 years and median survival 17.6 years. Age at spinal neurological lesion onset was found to be the only factor with a significant effect on survival. Of the 148 patients who had Frankel grades A, B, or C on admission, 58% achieved recovery to grades D and E. Frankel grade at admission, age, and spinal neurological level had a significant effect on recovery. The mean length of stay was 99.7 days, and only Frankel grade had a significant effect on length of stay. CONCLUSIONS: Patients with spinal stenosis and disabling spinal neurological lesions can achieve significant neurological recovery and survive for many years. They require adequate care in a specialist rehabilitation system.

Cauda Equina↗
PubMed2005

Perisylvian language networks of the human brain.

Early anatomically based models of language consisted of an arcuate tract connecting Broca's speech and Wernicke's comprehension centers; a lesion of the tract resulted in conduction aphasia. However, the heterogeneous clinical presentations of conduction aphasia suggest a greater complexity of perisylvian anatomical connections than allowed for in the classical anatomical model. This article re-explores perisylvian language connectivity using in vivo diffusion tensor magnetic resonance imaging tractography. Diffusion tensor magnetic resonance imaging data from 11 right-handed healthy male subjects were averaged, and the arcuate fasciculus of the left hemisphere reconstructed from this data using an interactive dissection technique. Beyond the classical arcuate pathway connecting Broca's and Wernicke's areas directly, we show a previously undescribed, indirect pathway passing through inferior parietal cortex. The indirect pathway runs parallel and lateral to the classical arcuate fasciculus and is composed of an anterior segment connecting Broca's territory with the inferior parietal lobe and a posterior segment connecting the inferior parietal lobe to Wernicke's territory. This model of two parallel pathways helps explain the diverse clinical presentations of conduction aphasia. The anatomical findings are also relevant to the evolution of language, provide a framework for Lichtheim's symptom-based neurological model of aphasia, and constrain, anatomically, contemporary connectionist accounts of language.

Adult↗
PubMedDate not supplied

Somatic (craniocervical) tinnitus and the dorsal cochlear nucleus hypothesis.

PURPOSE: Of all nonauditory sensory systems, only the somatosensory system seems to be related to tinnitus (eg, temporomandibular joint syndrome and whiplash). The purpose of this study is to describe the distinguishing characteristics of tinnitus associated with somatic events and to use these characteristics to develop a neurological model of somatic tinnitus. MATERIALS AND METHODS: Case series. RESULTS: Some patients with tinnitus, but no other hearing complaints, share several clinical features including (1) an associated somatic disorder of the head or upper neck, (2) localization of the tinnitus to the ear ipsilateral to the somatic disorder, (3) no vestibular complaints, and (4) no abnormalities on neurological examination. Pure tone and speech audiometry of the 2 ears is always symmetric and usually within normal limits. Based on these clinical features, it is proposed that somatic (craniocervical) tinnitus, like otic tinnitus, is caused by disinhibition of the ipsilateral dorsal cochlear nucleus. Nerve fibers whose cell bodies lie in the ipsilateral medullary somatosensory nuclei mediate this effect. These neurons receive inputs from nearby spinal trigeminal tract, fasciculus cuneatus, and facial, vagal, and glossopharyngeal nerve fibers innervating the middle and external ear. CONCLUSIONS: Somatic (craniocervical) modulation of the dorsal cochlear nucleus may account for many previously poorly understood aspects of tinnitus and suggests novel tinnitus treatments.

Adult↗
PubMed2004

Comprehensive strategies to study neuronal function in transgenic animal models.

In the last 20 years of transgenic research, transgenic technology has been developed and refined to provide a seemingly comprehensive range of experimental approaches to questions of neuronal gene function; however, parallel developments in other technologies, such as whole genome sequencing and microarray analysis of gene expression, has meant that the questions have gotten harder. The complexity of neuronal systems and the difficulty of modeling neurologic diseases in rodents also present considerable challenges to molecular neuroscientists. Future functional genomic studies of brain and behavior will involve the full range of available transgenic methods and the incorporation of new technologies, including RNA interference.

Animals↗
PubMed2004

Recent advances in the pharmacology of neurological gene therapy.

The choice of vectors, transgenes, regulatory elements, delivery approaches and the capacity to transduce the appropriate target cell type all influence the effectiveness of gene therapy for neurological diseases. Furthermore, even if many strategies are sound and effective in experimental animals, issues relating to side effects of gene therapy, longevity of therapeutic transgene expression and diffusion throughout the brain can limit the clinical potential of gene therapy. During the past 12-18 months, there have been significant advances in the following areas: the capacity to target vectors to predetermined cells types; the development of gene therapy approaches for the treatment of dominant inherited and neurodegenerative diseases; the capacity to achieve systemic delivery of viral vectors to the brain; and the development of viral vectors to model neurological diseases.

Animals↗
PubMed2004

The nematode Caenorhabditis elegans as a model of organophosphate-induced mammalian neurotoxicity.

Fifteen organic phosphate pesticides were tested by computer tracking for their acute behavioral toxicity with the nematode Caenorhabditis elegans. Thirteen of these 15 chemicals are used as insecticides and are anticholesterase agents. The other two chemicals are used as herbicides. EC50 values for each chemical were compared to the corresponding LD50 acute lethality value in rats and mice. Order of toxicity was found to be significantly correlated in comparisons of C. elegans to both rats and mice. Mechanistic investigations were conducted by assaying 8 of the 15 chemicals for anticholinesterase activity in C. elegans. Significant cholinesterase inhibition was confirmed for five chemicals that had displayed high behavioral toxicity, while three chemicals of low behavioral toxicity showed no significant decrease in cholinesterase activity. Toxicity for two chemicals that do not inhibit cholinesterase in mammals was linked to pH effects. Detailed comparison of individual chemicals and metabolic issues are discussed. These results have positive implications for the use of C. elegans as a mammalian neurological model and support the use of C. elegans in early rounds of chemical toxicity screening.

Animals↗