Architecture of Neuropsychiatric Disease: Highlights of the 15th Annual Meeting of the American Neuropsychiatric Association, February 21-24, 2004, Bal Harbour, FL

Reviews in Neurological Diseases. 2004  |  Pubmed ID: 16400281

Preclinical Evaluation of a Novel Intracerebral Microinjection Instrument Permitting Electrophysiologically Guided Delivery of Therapeutics

Neurosurgery. Jun, 2004  |  Pubmed ID: 15157308

This series of studies was designed to evaluate the function of a new neurosurgical instrument for precision injection of therapeutics within the central nervous system.

A Versatile, Low-cost Adaptor for Stereotaxic and Electrophysiologic Spinal Preparations in Juvenile and Adult Rodents

Brain Research Bulletin. Dec, 2005  |  Pubmed ID: 16325015

Rats and mice provide excellent models for normal spinal cord physiology, traumatic spinal cord injury, and various disease states. Alternative and improved methodologies for experimental spinal preparations are desirable, particularly in the wake of expanding neuroscience technology, such as the diverse array of transgenic mice now available, and exciting new therapeutic approaches, including transplantation and gene therapy. This report describes a simple, low-cost instrument for spinal preparations in rodents of different sizes, including rat pups. The device adapts to standard small animal stereotaxic instruments, precluding the need for additional stereotaxic apparatus. Surgical methods utilizing the device are presented demonstrating the instrument's capacity for precise alignment and stabilization of the spinal column that is reproducible from animal to animal. Proof of concept is demonstrated with results from spinal cord injections and electrophysiologic recordings.

Coalescence of Psychiatry, Neurology, and Neuropsychology: from Theory to Practice

Harvard Review of Psychiatry. May-Jun, 2006  |  Pubmed ID: 16787885

In a climate of renewed interest in the synergy between neurology and psychiatry, practitioners are increasingly recognizing the importance of exchange and collaboration between these two disciplines. However, there are few working models of interdisciplinary teams that freely share expertise in real time, while providing clinical and academic training to future physicians who specialize in the central nervous system. Over the past 11 years, the McLean Hospital Neuropsychiatry and Behavioral Neurology service has provided proof-of-principle for such collaboration, demonstrating that a team comprising psychiatrists, neurologists, and neuropsychologists can function effectively as a unit while maintaining the autonomy of these three disciplines and also synthesizing their combined knowledge. In addition to delivering enhanced patient care and promoting medical research, this clinical service has provided enriched cross-specialty training for fellows, residents, and medical students. The practical functioning of the team is described, and case vignettes are presented to illustrate the team's collaborative synergism in practice.

Mechanisms of Mind: Highlights of the 17th Annual Meeting of the American Neuropsychiatric Association, February 18-21, 2006, San Diego, CA

Reviews in Neurological Diseases. 2006  |  Pubmed ID: 17047578

Points of interest from the 17th Annual American Neuropsychiatric Association are reviewed, including several cognitive neuroscience frameworks that have been proposed to account for the neural basis of moral cognition. Also discussed are the brain mechanisms behind creative innovation, and an overview is presented of several of this year's outstanding contributions to clinical and basic neuroscience.

Zincergic Innervation of Medial Prefrontal Cortex by Basolateral Projection Neurons

Neuroreport. Apr, 2007  |  Pubmed ID: 17413652

The basolateral amygdaloid complex is a site of origin for zinc-containing pathways in the brain; it is also known for its massive innervation of the medial prefrontal cortex. The presence, and potential neuromodulatory role, of zinc within this fundamental corticolimbic circuit has not been described. For this study, basolateral neurons innervating the medial prefrontal cortex were retrogradely labeled with FluoroGold, and zinc-containing neurons were identified using autometallography to visualize zinc selenium precipitates. Upon quantification of single-labeled and double-labeled cells, 35% of basolateral neurons projecting to medial prefrontal cortex were found to also contain zinc. We conclude that zinc may act as a neuromodulator for a substantial proportion of basolateral-medial prefrontal cortical innervation, therefore implicating zinc in corticolimbic function as well as pathology.

Antidepressant Effect of Stem Cell-derived Monoaminergic Grafts

Neuroreport. Oct, 2007  |  Pubmed ID: 17921864

In this study, we demonstrate that embryonic stem cells can be engineered to differentiate into high percentages of serotonergic and dopaminergic neurons. In vitro, these cells release serotonin and dopamine in response to membrane depolarization. Upon engraftment into the medial prefrontal cortex in rats, the homolog of the human anterior cingulate cortex, the cells assumed neuronal morphologies, expressed monoaminergic-specific proteins, and seemed to functionally integrate, as assessed by the upregulation of the immediate-early gene, cfos. Furthermore, the transplanted animals performed in a manner similar to that of animals that received the antidepressant, citalopram, when administered the forced swim test, a validated model of human depression. These results suggest that transplantation of customized stem cells might perhaps be useful in the study treatment of psychiatric disorders.

Increasing Interaction of Amygdalar Afferents with GABAergic Interneurons Between Birth and Adulthood

Cerebral Cortex (New York, N.Y. : 1991). Jul, 2008  |  Pubmed ID: 17971342

Previous work in animal models has shown that projections from the basolateral amygdala (BLA) progressively infiltrate the medial prefrontal cortex (mPFC) from birth to adulthood, with the most dramatic sprouting occurring during the postweanling period. GABAergic (gamma-aminobutyric acidergic) interneurons in the human homolog of the rat mPFC have been implicated in the pathophysiology of schizophrenia, an illness with an onset that is delayed until late adolescence. Here we investigated the interaction of BLA fibers with mPFC GABAergic interneurons from postnatal day 6 (P6) to P120 using anterograde tracing and immunocytochemistry. We found a 3-fold increase in axosomatic and an 8-fold increase in axo-dendritic contacts in both layers II and V of the mPFC. Ultrastructural analysis using a colloidal gold immunolocalization demonstrated that the greatest proportion of BLA appositions were with GABA-negative spines (30.8%) and GABA-positive dendritic shafts (35.5%). Although GABA-negative interactions demonstrated well-defined axo-spinous synapses, membrane specializations could not be identified with confidence in GABA-positive elements. Our findings suggest that GABAergic interneurons are major targets for BLA fibers projecting to the mPFC. The establishment of this circuitry, largely during adolescence, may contribute to the integration of emotional responses with attentional and other cognitive processes mediated within this region during corticolimbic development.

Amygdala-dependent Regulation of Electrical Properties of Hippocampal Interneurons in a Model of Schizophrenia

Biological Psychiatry. Mar, 2009  |  Pubmed ID: 19027103

Schizophrenia (SZ) involves dysfunction of gamma-aminobutyric acid (GABA)ergic transmission in the hippocampus (HIPP), particularly in sector CA2/3. Previous work using a rodent model of postmortem abnormalities in SZ demonstrated that activation of the basolateral amygdala (BLA) results in decreases of GABA currents in pyramidal neurons of CA2/3 but not CA1. In addition, a decrease of GABA cells has been reported in postmortem studies of the HIPP in SZ. In the present work we tested the hypothesis that BLA activation in this rodent model of SZ leads to changes in the electrical properties of interneurons located in sector CA2/3.

An Atypical Presentation of Anton Syndrome in a Patient with Preserved Cognition Despite Multiple Cerebral Infarcts: a Case Report

CNS Spectrums. Jan, 2009  |  Pubmed ID: 19169184

Zinc: the Brain's Dark Horse

Synapse (New York, N.Y.). Nov, 2009  |  Pubmed ID: 19623531

Zinc is a life-sustaining trace element, serving structural, catalytic, and regulatory roles in cellular biology. It is required for normal mammalian brain development and physiology, such that deficiency or excess of zinc has been shown to contribute to alterations in behavior, abnormal central nervous system development, and neurological disease. In this light, it is not surprising that zinc ions have now been shown to play a role in the neuromodulation of synaptic transmission as well as in cortical plasticity. Zinc is stored in specific synaptic vesicles by a class of glutamatergic or "gluzinergic" neurons and is released in an activity-dependent manner. Because gluzinergic neurons are found almost exclusively in the cerebral cortex and limbic structures, zinc may be critical for normal cognitive and emotional functioning. Conversely, direct evidence shows that zinc might be a relatively potent neurotoxin. Neuronal injury secondary to in vivo zinc mobilization and release occurs in several neurological disorders such as Alzheimer's disease and amyotrophic lateral sclerosis, in addition to epilepsy and ischemia. Thus, zinc homeostasis is integral to normal central nervous system functioning, and in fact its role may be underappreciated. This article provides an overview of zinc neurobiology and reviews the experimental evidence that implicates zinc signals in the pathophysiology of neuropsychiatric diseases. A greater understanding of zinc's role in the central nervous system may therefore allow for the development of therapeutic approaches where aberrant metal homeostasis is implicated in disease pathogenesis.

New-onset Dissociative Disorder After Electroconvulsive Therapy

The Journal of ECT. Sep, 2010  |  Pubmed ID: 19935087

Electroconvulsive therapy (ECT) is an exceptionally effective treatment for a number of psychiatric conditions; however, a common adverse effect is temporary cognitive impairment, especially memory loss. The dissociative disorders also involve disturbances of memory, as well as consciousness and personal identity, but are rarely iatrogenic. We report a case in which dissociative symptoms developed after ECT. A 51-year-old woman with hypothyroidism, migraine headaches, bipolar disorder, and anorexia by history was admitted for worsening depression with suicidal ideation. After a course of 7 right-sided ECT treatments, she experienced remarkable personality change, claiming that it was 1976 and behaving as though she was 30 years younger. Neuropsychological tests were normal, and her memory and former personality spontaneously returned 2 weeks later. This case illustrates that such events may be seen in patients with certain psychiatric profiles, and further studies are needed to determine the risk factors for the occurrence of dissociative episodes after ECT.

Safety and Function of a New Clinical Intracerebral Microinjection Instrument for Stem Cells and Therapeutics Examined in the Göttingen Minipig

Stereotactic and Functional Neurosurgery. 2010  |  Pubmed ID: 20051711

A new intracerebral microinjection instrument (IMI) allowing multiple electrophysiologically guided microvolume injections from a single proximal injection path in rats has been adapted to clinical use by coupling the IMI to an FHC microTargeting Manual Drive, designed to be used with standard stereotactic frame-based systems and FHC frameless microTargeting Platforms.

Convection Enhanced Drug Delivery of BDNF Through a Microcannula in a Rodent Model to Strengthen Connectivity of a Peripheral Motor Nerve Bridge Model to Bypass Spinal Cord Injury

Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. Jan, 2012  |  Pubmed ID: 22266141

Models employing peripheral nerve to bypass spinal cord injury (SCI), although highly promising, may benefit from improved nerve regeneration and motor bridge connectivity. Recent studies have demonstrated that neuronal growth factor-induced enhancement of endogenous neurorestoration may improve neuronal connectivity after severe neurologic injury, particularly if delivered intraparenchymally with zero-order kinetics. We sought to investigate the effect of convection-enhanced delivery of brain-derived neurotrophic factor (BDNF), a neuronal growth factor, on the connectivity of a peripheral motor-nerve bridge in a rodent model using electrophysiology and immunohistochemistry (IHC). Spinal cords of 29 female rats were hemisected at the L1 level. Ipsilateral T13 peripheral nerves were dissected from their muscular targets distally, while maintaining their connections with the spinal cord, and inserted caudal to the injury site to establish the nerve bridge. A microcannula attached to a six-week mini-osmotic pump was used to deliver either BDNF (n=12), saline (n=14), or fluorescein dye (n=3) directly into the spinal cord parenchyma between the site of nerve insertion and hemisection to a depth of 2mm into the area of the lateral motor pool. After four weeks, gastrocnemius muscle activation was assessed electromyographically in five animals from each group. Spinal cords were harvested and analyzed with IHC for cannula-associated injury, and nerve regeneration. Strength of motor bridge connection was illustrated by electrophysiology data. Intraspinal BDNF levels were measured using enzyme-linked immunosorbent assay. IHC revealed increased intraparenchymal BDNF concentration at the nerve bridge insertion site with evidence of minimal trauma from cannulation. BDNF infusion resulted in stronger connections between bridge nerves and spinal motor axons. Bridge nerve electrical stimulation in BDNF-treated rats evoked hind leg electromyogram responses of shorter latency and larger amplitudes than saline-infused controls. Thus, direct convection-assisted delivery provides reliable administration of potent growth factors directly into the spinal cord parenchyma. Delivery of BDNF at the peripheral nerve bridge site results in enhanced connectivity of the peripheral motor bridge in a rodent model of SCI.