Posts Tagged Pathophysiology

[Abstract + References] Neuron–glia interactions in the pathophysiology of epilepsy

Abstract

Epilepsy is a neurological disorder afflicting ~65 million people worldwide. It is caused by aberrant synchronized firing of populations of neurons primarily due to imbalance between excitatory and inhibitory neurotransmission. Hence, the historical focus of epilepsy research has been neurocentric. However, the past two decades have enjoyed an explosion of research into the role of glia in supporting and modulating neuronal activity, providing compelling evidence of glial involvement in the pathophysiology of epilepsy. The mechanisms by which glia, particularly astrocytes and microglia, may contribute to epilepsy and consequently could be harnessed therapeutically are discussed in this Review.

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via Neuron–glia interactions in the pathophysiology of epilepsy | Nature Reviews Neuroscience

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[ARTICLE] Stroke recovery and rehabilitation in 2016: a year in review of basic science and clinical science – Full Text

Introduction

Advances in acute stroke treatment and the widespread establishment of dedicated stroke units have resulted in an increase in poststroke survival and life expectancy. However, stroke remains a leading cause of long-term disability worldwide, making the improvement of poststroke outcomes a chief healthcare goal for many countries. The current strategies strive to reduce the initial injury by acutely implementing thrombolytic and/or endovascular interventions, to better understand the major determinants that influence the stroke recovery and to search for innovative, effective and accessible recovery and rehabilitation modalities that can mitigate various poststroke deficits and enhance the quality of life. These approaches require a collaboration and integration of fundamental and clinical science research to more efficiently translate benchwork results into therapeutic bedside interventions. Due to a variety of stroke research advances in both the basic and clinical sciences over the last few years, especially in 2016, the field of stroke recovery and rehabilitation has celebrated many hopes and progresses. Our goal was to explore these studies and better identify, understand and integrate key findings for the purpose of identifying new targets that could be translated into clinically rewarding therapeutic interventions in future.

We manually searched professional journals with an average 5-year impact factor >3 (from 2012 to 2016) that were known to publish manuscript with topics in stroke recovery and rehabilitation. We aimed to selectively highlight relevant basic and clinical science stroke recovery research published between December 2015 and December 2016 in these journals. Certain selection biases cannot be completely ruled out and omissions are possible. The list of journals are Science, Nature, Nature Neuroscience, Neuron, Proceedings of the National Academy of Sciences of the United States of America, Neurobiology of Disease, Scientific Report, PLOS ONE, Acta Neuropathologica, Journal of Neuroscience, Annals of Neurology, Neurology, JAMA Neurology, Stroke, The Lancet, Lancet of Neurology, JAMA, Brain, Brain Stimulation, Stem Cells, Cell Death and Differentiation, Neurorehabilitation and Neural Repair, Journal of Cerebral Blood Flow and Metabolism and New England Journal of Medicine.

Continue —> Stroke recovery and rehabilitation in 2016: a year in review of basic science and clinical science | Stroke and Vascular Neurology

 

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[WEB SITE] ADD Program receives $19.5 million NIH contract to test drugs for treating epilepsy

The University of Utah College of Pharmacy’s Anticonvulsant Drug Development (ADD) Program has been awarded a five-year $19.5 million contract renewal with the National Institutes of Health (NIH) to test drugs to treat epilepsy, and the major focus of the project is to address needs that affect millions of people worldwide -identify novel investigational compounds to prevent the development of epilepsy or to treat refractory, or drug-resistant, epilepsy.

The ADD program began in 1975 and since then has tested the vast majority of drugs used to control seizures in patients with epilepsy, helping millions of people worldwide. Unfortunately, almost one-third of the estimated 50 million people with the disorder has refractory, or unresponsive, epilepsy that isn’t adequately controlled by medications currently available. The contract renewal, awarded through the National Institute of Neurological Disorders and Stroke (NINDS) to the U Department of Pharmacology and Toxicology, represents a shift in the mission to identify new therapies, according to ADD Director Karen S. Wilcox, Ph.D., professor and chair of pharmacology and toxicology and principal investigator of the contract.

“We’re proud that over the past 41 years, the ADD program has played a key role in identifying and characterizing many of the drugs now available to treat patients with epilepsy and to control their seizures,” Wilcox says. “Now, we’re looking for drugs that can modify or prevent the disease, particularly in those patients either with refractory epilepsy or at risk for developing epilepsy following a brain injury.”

Epilepsy is a group of neurological disorders characterized by a tendency for repeated seizures over time. It occurs when permanent changes in the brain result in abnormal or excessive neuronal activity in the brain. An estimated 2.9 million people in the United States and 50 million people worldwide have active epilepsy, according the Centers for Disease Control and World Health Organization. There is no cure for epilepsy and the mainstay of treatment is anti-seizure medications.

ADD is a long-standing program dedicated to testing drugs to treat epilepsy. It has received continuous funding from NINDS’ Epilepsy Therapy Screening Program (ETSP) (formerly known as the Anticonvulsant Screening Program) since its founding in 1974. In collaboration, the ETSP and the ADD Program have evaluated more than 32,000 compounds. ADD received the contract in a competitive bidding process. The renewal of the contractual relationship between the NINDS and the University of Utah reflects the ongoing commitment of the NIH and the ETSP to finding and developing novel therapies for epilepsy and represents a unique partnership between government, industry, and academia.

“The NIH-NINDS ETSP is pleased to continue the productive relationship with the University of Utah,” says Dr. John Kehne, a Program Director at NINDS and head of the ETSP. “These and other efforts supported by the NINDS will help to discover new pharmacotherapies to address the unmet medical needs of people living with epilepsy.”

In addition to its focus on evaluating potential candidate drugs for the treatment of therapy-resistant epilepsy, the mission of the ADD Program includes efforts to identify novel therapies for different types of epilepsy. The program also serves as a base for innovative basic research that sheds new light on the pathophysiology of epilepsy and provides a unique training environment for students, research fellows, and visiting scientists. Currently, the ADD program employ18 researchers, technicians, and staff. Cameron S. Metcalf, Ph.D is associate director and a co-Investigator of the contract and Peter J. West, Ph.D., and Misty D. Smith, Ph.D, research assistant professors of pharmacology and toxicology, are also co-investigators on the contract renewal.

Although there currently is no cure for epilepsy, Wilcox, who previously served as a co-Investigator of ADD before taking over as PI in 2016, believes that can be changed.

“The brain has remarkable plasticity throughout a person’s life,” she says. “If we learn enough about neuroscience and the details of how the brain works, it’s very possible to find a cure.”

Source: University of Utah Health Sciences

Source: ADD Program receives $19.5 million NIH contract to test drugs for treating epilepsy

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[ARTICLE] Gait post-stroke: Pathophysiology and rehabilitation strategies

Summary

 

We reviewed neural control and biomechanical description of gait in both non-disabled and post-stroke subjects. In addition, we reviewed most of the gait rehabilitation strategies currently in use or in development and observed their principles in relation to recent pathophysiology of post-stroke gait.

In both non-disabled and post-stroke subjects, motor control is organized on a task-oriented basis using a common set of a few muscle modules to simultaneously achieve body support, balance control, and forward progression during gait.

Hemiparesis following stroke is due to disruption of descending neural pathways, usually with no direct lesion of the brainstem and cerebellar structures involved in motor automatic processes. Post-stroke, improvements of motor activities including standing and locomotion are variable but are typically characterized by a common postural behaviour which involves the unaffected side more for body support and balance control, likely in response to initial muscle weakness of the affected side.

Various rehabilitation strategies are regularly used or in development, targeting muscle activity, postural and gait tasks, using more or less high-technology equipment. Reduced walking speed often improves with time and with various rehabilitation strategies, but asymmetric postural behaviour during standing and walking is often reinforced, maintained, or only transitorily decreased. This asymmetric compensatory postural behaviour appears to be robust, driven by support and balance tasks maintaining the predominant use of the unaffected side over the initially impaired affected side.

Based on these elements, stroke rehabilitation including affected muscle strengthening and often stretching would first need to correct the postural asymmetric pattern by exploiting postural automatic processes in various particular motor tasks secondarily beneficial to gait.

Source: Gait post-stroke: Pathophysiology and rehabilitation strategies

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