Time filter

Source Type

Portland, United States

Boison D.,Legacy Research
Epilepsia | Year: 2010

Deficiency of the brain's endogenous anticonvulsant adenosine is a pathologic hallmark of epilepsy. Consequently, focal adenosine augmentation therapies (AATs) constitute a rational approach for seizure suppression. Focal adenosine augmentation and resulting seizure suppression can be realized by implanting adenosine-releasing stem cells or polymers into epileptogenic brain regions. For an expanded treatment of this topic see Jasper's basic mechanisms of the epilepsies. 4th ed. (Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, eds) published by Oxford University Press (available on the National Library of Medicine Bookshelf [NCBI] at). © 2010 International League Against Epilepsy. Source

Pritchard E.M.,Tufts University | Valentin T.,Tufts University | Boison D.,Legacy Research | Kaplan D.L.,Tufts University
Biomaterials | Year: 2011

Controlling the rate of silk degradation is critical to its potential use in biomedical applications, including drug delivery and tissue engineering. The effect of protease concentration on accelerating degradation, and the use of ethylenediamine tetraacetic acid (EDTA) on reducing rates of degradation and on drug release from silk-based drug carriers was studied. Increased rates of proteolysis resulted in increased dye release from silk carriers, while EDTA release from the silk carriers inhibited proteolysis. The sustained release of EDTA from silk carriers in combination with the release of the small molecule anti-convulsant adenosine was investigated in vitro. This combination of factors resulted in delayed release of adenosine by inhibiting proteolytic activity. These results introduce a promising strategy to control drug delivery through the regulation of silk degradation rate, achieved via manipulation of local proteolytic activity. This ability to modulate enzyme function could be applicable to a range of silk biomaterial formats as well as other biodegradable polymers where enzymatic functions control biomaterial degradation and drug release rates. © 2010 Elsevier Ltd. Source

Boison D.,Legacy Research
Epilepsia | Year: 2010

Since its discovery a decade ago, RNA interference (RNAi) has been developed not only into powerful experimental tools but also into promising novel therapeutics. In contrast to conventional antiepileptic drugs (AEDs) that target specific proteins such as ion channels or receptors, RNAi-based therapeutics exploit an endogenous regulatory mechanism of gene expression and thereby are poised to prevent or reverse pathogenetic mechanisms involved in seizure development. Therapeutic RNAi has been widely explored for dominant targets involved in neurodegenerative diseases; however, their use for epilepsy therapy has received less attention. This review discusses potential RNAi-based targets that are of interest for epilepsy therapy, including adenosine kinase (ADK), the key negative regulator of the brain's endogenous anticonvulsant adenosine. Overexpression of ADK, and the resulting adenosine deficiency, are pathologic hallmarks of the sclerotic epileptic brain, and have been implicated in seizure generation. Therefore, RNAi-strategies aimed at reducing ADK (and increasing adenosine) are based on a direct neurochemical rationale that has recently been explored experimentally using ex vivo and in vivo gene therapy approaches. Technical issues and challenges remain before those promising tools can be developed into future therapeutics for epilepsy. © 2010 International League Against Epilepsy. Source

Saugstad J.A.,Legacy Research
Journal of Cerebral Blood Flow and Metabolism | Year: 2010

MicroRNAs are small RNAs that function as regulators of posttranscriptional gene expression. MicroRNAs are encoded by genes, and processed to form ribonucleoprotein complexes that bind to messenger RNA (mRNA) targets to repress translation or degrade mRNA transcripts. The microRNAs are particularly abundant in the brain where they serve as effectors of neuronal development and maintenance of the neuronal phenotype. They are also expressed in dendrites where they regulate spine structure and function as effectors in synaptic plasticity. MicroRNAs have been evaluated for their roles in brain ischemia, traumatic brain injury, and spinal cord injury, and in functional recovery after ischemia. They also serve as mediators in the brain's response to ischemic preconditioning that leads to endogenous neuroprotection. In addition, microRNAs are implicated in neurodegenerative disorders, including Alzheimer's, Huntington, Parkinson, and Prion disease. The discovery of microRNAs has expanded the potential for human diseases to arise from genetic mutations in microRNA genes or sequences within their target mRNAs. This review discusses microRNA discovery, biogenesis, mechanisms of gene regulation, their expression and function in the brain, and their roles in brain ischemia and injury, neuroprotection, and neurodegeneration. © 2010 ISCBFM All rights reserved. Source

Boison D.,Legacy Research | Chen J.-F.,Boston University | Fredholm B.B.,Karolinska Institutet
Cell Death and Differentiation | Year: 2010

Despite major advances in a variety of neuroscientific research fields, the majority of neurodegenerative and neurological diseases are poorly controlled by currently available drugs, which are largely based on a neurocentric drug design. Research from the past 5 years has established a central role of glia to determine how neurons function and, consequently, glial dysfunction is implicated in almost every neurodegenerative and neurological disease. Glial cells are key regulators of the brain's endogenous neuroprotectant and anticonvulsant adenosine. This review will summarize how glial cells contribute to adenosine homeostasis and how glial adenosine receptors affect glial function. We will then move on to discuss how glial cells interact with neurons and the vasculature, and outline new methods to study glial function. We will discuss how glial control of adenosine function affects neuronal cell death, and its implications for epilepsy, traumatic brain injury, ischemia, and Parkinson's disease. Eventually, glial adenosine-modulating drug targets might be an attractive alternative for the treatment of neurodegenerative diseases. There are, however, several major open questions that remain to be tackled. © 2010 Macmillan Publishers Limited All rights reserved. Source

Discover hidden collaborations