Bryan E. Figueroa
Harvard University
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Publication
Featured researches published by Bryan E. Figueroa.
The Journal of Neuroscience | 2004
Shan Zhu; Mingwei Li; Bryan E. Figueroa; Aijian Liu; Irina G. Stavrovskaya; Piera Pasinelli; M. Flint Beal; Robert H. Brown; Bruce S. Kristal; Robert J. Ferrante; Robert M. Friedlander
Creatine mediates remarkable neuroprotection in experimental models of amyotrophic lateral sclerosis, Huntingtons disease, Parkinsons disease, and traumatic brain injury. Because caspase-mediated pathways are shared functional mechanistic components in these diseases, as well as in ischemia, we evaluated the effect of creatine supplementation on an experimental stroke model. Oral creatine administration resulted in a remarkable reduction in ischemic brain infarction and neuroprotection after cerebral ischemia in mice. Postischemic caspase-3 activation and cytochrome c release were significantly reduced in creatine-treated mice. Creatine administration buffered ischemia-mediated cerebral ATP depletion. These data provide the first direct correlation between the preservation of bioenergetic cellular status and the inhibition of activation of caspase cell-death pathways in vivo. An alternative explanation to our findings is that creatine is neuroprotective through other mechanisms that are independent of mitochondrial cell-death pathways, and therefore postischemic ATP preservation is the result of tissue spearing. Given its safety record, creatine might be considered as a novel therapeutic agent for inhibition of ischemic brain injury in humans. Prophylactic creatine supplementation, similar to what is recommended for an agent such as aspirin, may be considered for patients in high stroke-risk categories.
The Journal of Neuroscience | 2009
Rona K. Graham; Mahmoud A. Pouladi; Prasad R. Joshi; Ge Lu; Yu Deng; Nanping Wu; Bryan E. Figueroa; Martina Metzler; Véronique M. André; Elizabeth J. Slow; Lynn A. Raymond; Robert M. Friedlander; Michael S. Levine; Blair R. Leavitt; Michael R. Hayden
Huntington disease (HD) is a neurodegenerative disorder caused by an expanded CAG tract in the HD gene. Polyglutamine expansion of huntingtin (htt) results in early, progressive loss of medium spiny striatal neurons, as well as cortical neurons that project to the striatum. Excitotoxicity has been postulated to play a key role in the selective vulnerability of striatal neurons in HD. Early excitotoxic neuropathological changes observed in human HD brain include increased quinolinate (QUIN) concurrent with proliferative changes such as increased spine density and dendritic length. In later stages of the disease, degenerative-type changes are apparent, such as loss of dendritic arborization, a reduction in spine density and reduced levels of 3-hydroxykynurenine and QUIN. It is currently unknown whether sensitivity to excitotoxic stress varies between initiation and progression of disease. Here, we have assessed the excitotoxic phenotype in the YAC128 mouse model of HD by examining the response to excitotoxic stress at different stages of disease. Our results demonstrate that YAC128 mice display enhanced sensitivity to NMDA ex vivo and QUIN in vivo before obvious phenotypic changes. In contrast, 10-month-old symptomatic YAC128 mice are resistant to QUIN-induced neurotoxicity. These findings are paralleled by a significant increase in NMDAR-mediated membrane currents in presymptomatic YAC128 dissociated medium spiny neurons progressing to reduced NMDAR-mediated membrane currents with disease progression. These data highlight the dynamic nature of the mutant htt-mediated excitotoxic phenotype and suggests that therapeutic approaches to HD may need to be altered, depending on the stage and development of the disease.
Stroke | 2009
Xin Wang; Bryan E. Figueroa; Irina G. Stavrovskaya; Yi Zhang; Ana C. Sirianni; Shan Zhu; Arthur L. Day; Bruce S. Kristal; Robert M. Friedlander
BACKGROUND AND PURPOSE The identification of a neuroprotective drug for stroke remains elusive. Given that mitochondria play a key role both in maintaining cellular energetic homeostasis and in triggering the activation of cell death pathways, we evaluated the efficacy of newly identified inhibitors of cytochrome c release in hypoxia/ischemia induced cell death. We demonstrate that methazolamide and melatonin are protective in cellular and in vivo models of neuronal hypoxia. METHODS The effects of methazolamide and melatonin were tested in oxygen/glucose deprivation-induced death of primary cerebrocortical neurons. Mitochondrial membrane potential, release of apoptogenic mitochondrial factors, pro-IL-1beta processing, and activation of caspase -1 and -3 were evaluated. Methazolamide and melatonin were also studied in a middle cerebral artery occlusion mouse model. Infarct volume, neurological function, and biochemical events were examined in the absence or presence of the 2 drugs. RESULTS Methazolamide and melatonin inhibit oxygen/glucose deprivation-induced cell death, loss of mitochondrial membrane potential, release of mitochondrial factors, pro-IL-1beta processing, and activation of caspase-1 and -3 in primary cerebrocortical neurons. Furthermore, they decrease infarct size and improve neurological scores after middle cerebral artery occlusion in mice. CONCLUSIONS We demonstrate that methazolamide and melatonin are neuroprotective against cerebral ischemia and provide evidence of the effectiveness of a mitochondrial-based drug screen in identifying neuroprotective drugs. Given the proven human safety of melatonin and methazolamide, and their ability to cross the blood-brain-barrier, these drugs are attractive as potential novel therapies for ischemic injury.
The Journal of Neuroscience | 2005
Xin Wang; Hongyan Wang; Bryan E. Figueroa; Wenhua Zhang; Chunfeng Huo; Yingjun Guan; Yu Zhang; Jean-Marie Bruey; John C. Reed; Robert M. Friedlander
Caspase-1 plays a role in the pathogenesis of a variety of neurological diseases. Caspase-1 activation is an early event in models of Huntingtons disease (HD). However, mechanisms regulating the activation of this apical caspase in cell death are not known. Receptor interacting protein-2 (Rip2) and caspase recruitment domain (CARD) only protein (Cop) are two CARD proteins with significant homology to the caspase-1 CARD and modulate caspase-1 activation in inflammation. Rip2 is a caspase-1 activator, and Cop is a caspase-1 inhibitor. We demonstrate in models of HD that caspase-1 activation results from dysregulation of caspase-1 activation pathways. Associated with disease progression, we detect elevation of the caspase-1 activator Rip2 and reduction of the caspase-1 inhibitor Cop. Knocking down endogenous Rip2/Cop respectively results in reduced/increased sensitivity to neurotoxic stimuli. Our data provide evidence that caspase-1-mediated cell death is regulated, at least in part, by the balance of Rip2 and Cop, and alterations of this balance may contribute to aberrant caspase-1-mediated pathogenesis in Huntingtons disease.
Neurosurgery | 2005
Bryan E. Figueroa; Robert M. Friedlander
Neurosurgery | 2005
Bryan E. Figueroa; Robert M. Friedlander
Neurosurgery | 2004
Bryan E. Figueroa; Robert M. Friedlander
Neurosurgery | 2004
Bryan E. Figueroa; Robert M. Friedlander
Neurosurgery | 2004
Bryan E. Figueroa; Robert M. Friedlander
Neurosurgery | 2004
Bryan E. Figueroa; Robert M. Friedlander