A5072837541- Intracranial Aneurysms: Treatment and Complications
- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
- Traumatic Brain Injury and Neurovascular Disturbances
- Vascular Malformations Diagnosis and Treatment
- Cerebrospinal fluid and hydrocephalus
- Cerebrovascular and Carotid Artery Diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Spinal Dysraphism and Malformations
- Neuroscience and Neuropharmacology Research
- Amyotrophic Lateral Sclerosis Research
- Intracerebral and Subarachnoid Hemorrhage Research
- Neurosurgical Procedures and Complications
- Cell death mechanisms and regulation
- Acute Ischemic Stroke Management
- Advanced Neuroimaging Techniques and Applications
- Meningioma and schwannoma management
- Spinal Cord Injury Research
- Circadian rhythm and melatonin
- Neurogenesis and neuroplasticity mechanisms
- Nerve injury and regeneration
- Neuroscience and Neural Engineering
- Fetal and Pediatric Neurological Disorders
- Neurological disorders and treatments
- Cholinesterase and Neurodegenerative Diseases
University of Pittsburgh
2016-2025
University of Pittsburgh Medical Center
2016-2025
Neurological Surgery
2016-2025
UPMC Health System
2023
Presbyterian Hospital
2011-2021
UPMC Presbyterian
2011-2021
Allegheny General Hospital
2021
University of Virginia
2020
University of Louisville
2020
University of Iowa
2020
Huntingtin is a 350-kilodalton protein of unknown function that mutated in Huntington's disease (HD), neurodegenerative disorder. The mutant presumed to acquire toxic gain detrimental striatal neurons the brain. However, loss beneficial activity wild-type huntingtin may also cause death neurons. Here we demonstrate up-regulates transcription brain-derived neurotrophic factor (BDNF), pro-survival produced by cortical necessary for survival We show this lost when becomes mutated, resulting...
The interleukin 1β converting enzyme (ICE) family plays a pivotal role in programmed cell death and has been implicated stroke neurodegenerative diseases. During reperfusion after filamentous middle cerebral artery occlusion, ICE-like cleavage products tissue immunoreactive (IL-1β) levels increased ischemic mouse brain. Ischemic injury decreased intracerebroventricular injections of protease inhibitors, N -benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD.FMK),...
Mutations in the copper/zinc superoxide dismutase (SOD1) gene produce an animal model of familial amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. To test new therapeutic strategy for ALS, we examined effect caspase inhibition transgenic mice expressing mutant human SOD1 with substitution glycine to alanine position 93 (mSOD1 G93A ). Intracerebroventricular administration zVAD-fmk, broad inhibitor, delays disease onset and mortality. Moreover, zVAD-fmk inhibits...
Minocycline is broadly protective in neurologic disease models featuring cell death and being evaluated clinical trials. We previously demonstrated that minocycline-mediated protection against caspase-dependent related to its ability prevent mitochondrial cytochrome c release. These results do not explain whether or how minocycline protects caspase-independent death. Furthermore, there no information on Smac/Diablo apoptosis-inducing factor might play a role chronic neurodegeneration. In...
G protein-coupled receptors (GPCRs) are classically characterized as cell-surface transmitting extracellular signals into cells. Here we show that central components of a GPCR signaling system comprised the melatonin type 1 receptor (MT
High-definition fiber tracking (HDFT) is a novel combination of processing, reconstruction, and tractography methods that can track white matter fibers from cortex, through complex crossings, to cortical subcortical targets with subvoxel resolution.To perform neuroanatomical validation HDFT investigate its neurosurgical applications.Six neurologically healthy adults 36 patients brain lesions were studied. Diffusion spectrum imaging data reconstructed Generalized Q-Ball Imaging approach....
Chronic inflammation is a pathologic feature of neurodegeneration and aging; however, the mechanism regulating this process not understood. Melatonin, an endogenous free radical scavenger synthesized by neuronal mitochondria, decreases with aging neurodegeneration. We proposed that insufficient melatonin levels impair mitochondrial homeostasis, resulting in DNA (mtDNA) release activation cytosolic DNA-mediated inflammatory response neurons. found increased oxidative stress decreased membrane...
To explore the role of interleukin (IL)-1β converting enzyme (ICE) in neuronal apoptosis, we designed a mutant ICE gene (C285G) that acts as dominant negative inhibitor. Microinjection into embryonal chicken dorsal root ganglial neurons inhibits trophic factor withdrawal–induced apoptosis. Transgenic mice expressing fused ICE-lacZ under control neuron specific enolase promoter appeared neurologically normal. These are deficient processing pro–IL-1β, indicating ICEC285G blocks function....
We investigated whether permeability transition-mediated release of mitochondrial cytochrome c is a potential therapeutic target for treating acute spinal cord injury (SCI). Based on previous reports, minocycline, second-generation tetracycline, exerts neuroprotection partially by inhibiting and reactive microgliosis. first evaluated at the epicenter after T10 contusive SCI in rats. Cytochrome peaked approximately 4-8 h postinjury. A dose-response study generated safe pharmacological regimen...
Caspase-1 plays an important functional role mediating neuronal cell death and dysfunction after experimental traumatic brain injury (TBI) in mice. Minocycline, a derivative of the antibiotic tetracycline, inhibits caspase-1 expression. This study investigates whether minocycline can ameliorate TBI-mediated Brains from mice subjected to underwent immunohistochemical analyses for caspase-1, caspase-3, specific marker (NeuN). Minocycline- saline-treated were compared with respect neurological...
We used transgenic mice expressing a dominant negative mutation of interleukin-1β converting enzyme (ICE) (C285G) in model transient focal ischemia order to investigate the role ICE ischemic brain damage. Transgenic mutant (n = 11) and wild-type littermates 9) were subjected 3 h middle cerebral artery occlusion followed by 24 reperfusion. Cerebral infarcts swelling reduced 44% 46%, respectively. Neurological deficits also significantly reduced. Regional CBF, blood pressure, core temperature,...
Many patients infected with human immunodeficiency virus-1 (HIV-1) develop a syndrome of neurologic deterioration known as HIV-associated dementia (HAD). Neurons are not productively by HIV-1; thus, the mechanism HIV-induced neuronal injury remains incompletely understood. Several investigators have observed evidence injury, including dendritic degeneration, and apoptosis in CNS tissue from HAD. Caspase enzymes, proteases associated process apoptosis, synthesized inactive proenzymes...
We report here that the activation of interleukin 1 beta (IL-1 beta)-converting enzyme (ICE) family is likely to be one crucial events tumor necrosis factor (TNF) cytotoxicity. The cowpox virus CrmA protein, a member serpin superfamily, inhibits enzymatic activity ICE and ICE-mediated apoptosis. HeLa cells overexpressing crmA are resistant apoptosis induced by Ice but not Ich-1, another Ice/ced-3 genes. found CrmA-expressing TNF-alpha/cycloheximide (CHX)-induced Induction in TNF-alpha/CHX...
Caspase-1 plays a key role in inflammatory pathways by processing pro-IL-1β into the active cytokine mature IL-1β. Given its sequence similarity with Caenorhabditis elegans cell death gene ced-3 ,it has long been speculated that caspase-1 may also play death. However, an unequivocal for questioned, and not definitively demonstrated. Furthermore, if does death, position apoptotic hierarchy clearly defined. Previous studies have shown knockout (KO) mice transgenic expressing dominant-negative...
Prointerleukin-1 beta (pro-IL-1 beta) is the only known physiologic substrate of interleukin-1 (IL-1 beta)-converting enzyme (ICE), founding member ICE/ced-3 cell death gene family. Since secreted mature IL-1 has been detected after apoptosis, we investigated whether this cytokine, when produced endogenously, plays a role in death. We found that hypoxia-induced apoptosis can be inhibited by either receptor antagonist (IL-1Ra) or neutralizing antibodies to its type 1 receptor. IL-1Ra also...