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Dennis M.,Program in Neurosciences and Mental Health | Dennis M.,University of Toronto

According to the 'Kennard Principle', there is a negative linear relation between age at brain injury and functional outcome. Other things being equal, the younger the lesioned organism, the better the outcome. But the 'Kennard Principle' is neither Kennard's nor a principle. In her work, Kennard sought to explain the factors that predicted functional outcome (age, to be sure, but also staging, laterality, location, and number of brain lesions, and outcome domain) and the neural mechanisms that altered the lesioned brain's functionality. This paper discusses Kennard's life and years at Yale (1931-1943); considers the genesis and scope of her work on early-onset brain lesions, which represents an empirical and theoretical foundation for current developmental neuropsychology; offers an historical explanation of why the 'Kennard Principle' emerged in the context of early 1970s work on brain plasticity; shows why uncritical belief in the 'Kennard Principle' continues to shape current research and practice; and reviews the continuing importance of her work. © 2009 Elsevier Srl. Source

Beggs S.,Program in Neurosciences and Mental Health | Beggs S.,University College London | Salter M.W.,Program in Neurosciences and Mental Health

The development and maintenance of the central nervous system is dependent upon regulated, homeostatic actions of microglia, which sculpt and refine neuronal circuitry. By contrast, dysregulation of microglia contributes to the pathology of neurodevelopmental disorders such as autism spectrum disorders; neurodegenerative disorders such as Alzheimer's disease; and schizophrenia and chronic neuropathic pain. © 2016 Elsevier Inc. Source

Lei S.,Program in Neurosciences and Mental Health | Lam W.-C.,University of Toronto
Canadian Journal of Ophthalmology

Objective To evaluate the efficacy and safety of dexamethasone (DEX) intravitreal implant (Ozurdex) in pediatric patients with cystoid macular edema (CME) refractory to conventional treatment. Design This study is a retrospective chart review. Participants Four pediatric patients (5 eyes) with CME caused by uveitis, type I idiopathic macular telangiectasia (IMT), or Coats disease treated with DEX intravitreal implant. Methods Medical records of the 4 pediatric patients (5 eyes) with CME included in this study were reviewed. Data collected included details of the underlying diseases, treatments, and pretreatment and post-treatment central retinal thickness (CRT) measured by time-domain optical coherence tomography, visual acuity (VA), intraocular pressure (IOP), and lens status. The median follow-up time was 65 weeks (range, 59-93 weeks). Results Fifteen DEX intravitreal implants were injected into 5 eyes over the follow-up period. Reduction of CME was achieved in all eyes within 12 weeks after the initial injection. VA improved in 4 eyes and was unchanged in 1 eye at 12 weeks; VA improved in 2 eyes, decreased in 2 eyes, and was unchanged in 1 eye at 52 weeks. Three of 5 eyes experienced IOP elevation ≥10 mm Hg during the follow-up period. IOP was ultimately controlled medically in all eyes. Significant lens opacification was documented in 2 eyes. Conclusions DEX intravitreal implant can be considered as an effective adjunctive off-label treatment to pediatric macular edema caused by uveitis or IMT/Coats disease; the safety profile of repeated treatment is acceptable. © 2015 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved. Source

Treble-Barna A.,University of Houston | Kulesz P.A.,University of Houston | Dennis M.,Program in Neurosciences and Mental Health | Fletcher J.M.,University of Houston
Journal of the International Neuropsychological Society

Covert orienting is related to the integrity of the midbrain, but the specificity of the relation is unclear. We compared covert orienting in three etiologies of congenital hydrocephalus (aqueductal stenosis [AS], Dandy-Walker malformation [DWM], and spina bifida myelomeningocele [SBM] - with and without tectal beaking) to explore the effects of midbrain and posterior fossa malformations. We hypothesized a stepwise order of group performance reflecting the degree of midbrain tectum dysmorphology. Performance on an exogenously cued covert orienting task was compared using repeated measures analysis of covariance, controlling for age. Individuals with SBM and tectal beaking demonstrated the greatest disengagement cost in the vertical plane, whereas individuals with AS performed as well as a typically developing (TD) group. Individuals with SBM but no tectal beaking and individuals with DWM showed greater disengagement costs in the vertical plane relative to the TD group, but better performance relative to the group with SBM and tectal beaking. Individuals with AS, DWM, and SBM and tectal beaking demonstrated poorer inhibition of return than TD individuals. Impairments in attentional disengagement in SBM are not attributable to the general effects of hydrocephalus, but are instead associated with specific midbrain anomalies that are part of the Chiari II malformation. Copyright © 2014 INS. Published by Cambridge University Press. Source

Salter M.W.,Program in Neurosciences and Mental Health | Salter M.W.,University of Toronto | Pitcher G.M.,Program in Neurosciences and Mental Health | Pitcher G.M.,University of Toronto
FEBS Journal

Upregulation of N-methyl-d-aspartate (NMDA) receptor function by the nonreceptor protein tyrosine kinase Src has been implicated in physiological plasticity at glutamatergic synapses. Here, we highlight recent findings suggesting that aberrant Src upregulation of NMDA receptors may also be key in pathophysiological conditions. Within the nociceptive processing network in the dorsal horn of the spinal cord, pathologically increased Src upregulation of NMDA receptors is critical for pain hypersensitivity in models of chronic inflammatory and neuropathic pain. On the other hand, in the hippocampus and prefrontal cortex, the physiological upregulation of NMDA receptors by Src is blocked by neuregulin 1-ErbB4 signaling, a pathway that is genetically implicated in the positive symptoms of schizophrenia. Thus, either over-upregulation or under-upregulation of NMDA receptors by Src may lead to pathological conditions in the central nervous system. Therefore, normalizing Src upregulation of NMDA receptors may be a novel therapeutic approach for central nervous system disorders, without the deleterious consequences of directly blocking NMDA receptors. © 2011 FEBS. Source

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