A5080439427- Traumatic Brain Injury and Neurovascular Disturbances
- Cardiac Arrest and Resuscitation
- Thermal Regulation in Medicine
- Cardiac Ischemia and Reperfusion
- Neuroinflammation and Neurodegeneration Mechanisms
- S100 Proteins and Annexins
- Anesthesia and Neurotoxicity Research
- Adenosine and Purinergic Signaling
- Neonatal and fetal brain pathology
- Mitochondrial Function and Pathology
- Traumatic Brain Injury Research
- Neuroscience of respiration and sleep
- Neonatal Respiratory Health Research
- Heme Oxygenase-1 and Carbon Monoxide
- Intensive Care Unit Cognitive Disorders
- Congenital Diaphragmatic Hernia Studies
- Fibroblast Growth Factor Research
- Nitric Oxide and Endothelin Effects
- Gut microbiota and health
- GDF15 and Related Biomarkers
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- RNA modifications and cancer
- Hemoglobin structure and function
- Phosphodiesterase function and regulation
- Clostridium difficile and Clostridium perfringens research
University of Pittsburgh
2014-2024
Children's Hospital of Pittsburgh
2005-2023
University Hospital of Bern
2023
University of Pittsburgh Medical Center
2007-2016
Center for Clinical Research (United States)
2005
Abstract Objective Enhanced lipid peroxidation is well established in traumatic brain injury. However, its molecular targets, identity of peroxidized phospholipid species, and their signaling role have not been deciphered. Methods Using controlled cortical impact as a model injury, we employed newly developed oxidative lipidomics approach to qualitatively quantitatively characterize the response. Results Electrospray ionization matrix‐assisted laser desorption/ionization mass spectrometry...
Traumatic brain injury (TBI) heterogeneity remains a critical barrier to translating therapies. Identifying final common pathways/molecular signatures that integrate this informs biomarker and therapeutic-target development. We present the first large-scale murine single-cell atlas of transcriptomic response TBI (334,376 cells) across clinically relevant models, sex, region, time as foundational step in molecularly deconstructing heterogeneity. Results were unique cell populations, regions,...
Manganese superoxide dismutase (MnSOD) provides the first line of defense against generated in mitochondria. SOD competes with nitric oxide for reaction and prevents generation peroxynitrite, a potent oxidant that can modify proteins to form 3-nitrotyrosine. Thus, sufficient amounts catalytically competent MnSOD are required prevent mitochondrial damage. Increased nitrotyrosine immunoreactivity has been reported after traumatic brain injury (TBI); however, specific protein targets containing...
Oxidative stress contributes to secondary damage after traumatic brain injury (TBI). Hypothermia decreases endogenous antioxidant consumption and lipid peroxidation experimental cerebral injury. Our objective was determine the effect of therapeutic hypothermia on oxidative severe TBI in infants children randomized moderate vs. normothermia.Prospective controlled study.Pediatric intensive care unit Pittsburgh Children's Hospital.The study included 28 patients.We compared effects (32 degrees...
Traumatic brain injury (TBI) alters microbial populations present in the gut, which may impact healing and tissue recovery. However, duration of these changes on outcome from TBI are unknown. Short-chain fatty acids (SCFAs), produced by bacterial fermentation dietary fiber, important signaling molecules microbiota gut-brain axis. We hypothesized that would lead to a sustained reduction SCFA producing bacteria, fecal SCFAs concentration, administration soluble improve functional after TBI....
We reported that adenosine A1 receptor (A1AR) knockout (KO) mice develop lethal status epilepticus after experimental traumatic brain injury (TBI), which is not seen in wild-type (WT) mice. Studies epilepsy, multiple sclerosis, and neuro-oncology suggest enhanced neuro-inflammation and/or neuronal death A1AR KO. hypothesized deficiency exacerbates the microglial response damage TBI. KO WT littermates were subjected to mild controlled cortical impact (3 m/sec; 0.5 mm depth) left parietal...
Hypotension after traumatic brain injury (TBI) worsens outcome. We published the first report of TBI plus hemorrhagic shock (HS) in mice using a volume-controlled approach and noted increased neuronal death. To rigorously control blood pressure during HS, pressure-controlled HS model is required. Our hypothesis was that brief, severe period will exacerbate functional deficits neuropathology versus or alone. C57BL6 male were randomized into four groups (n=10/group): sham, controlled cortical...
Cerebral edema is a key poor prognosticator in traumatic brain injury. There are no biomarkers identifying patients at-risk, or guiding mechanistically-precise therapies. Sulfonylurea receptor-1-transient receptor potential cation channel M4 upregulated only after injury, causing animal studies. We hypothesized that sulfonylurea receptor-1 measurable human cerebrospinal fluid severe injury and an informative biomarker of outcome.A total 119 samples were collected from 28 patients. Samples...
Cardiac arrest etiology may be an important source of between-patient heterogeneity, but the impact on organ injury is unknown. We tested hypothesis that asphyxial cardiac results in greater neurologic than (ventricular fibrillation arrest), whereas ventricular cardiovascular dysfunction after return spontaneous circulation.Prospective observational human and randomized animal study.University laboratory ICUs.Five-hundred forty-three patients admitted to ICU.Seventy-five male Sprague-Dawley...
Traumatic brain injury (TBI) from blast is often complicated by hemorrhagic shock (HS) in victims of terrorist attacks. Most studies HS after experimental TBI have focused on intracranial pressure; few explored the effect neuronal death TBI, and none been done mice. We hypothesized that CA1 hippocampus would be exacerbated TBI. C57BL6J male mice were anesthetized with isoflurane, mean arterial blood pressure (MAP) was monitored, controlled cortical impact (CCI) delivered to left parietal...
Objective: Resuscitation of hemorrhagic hypotension after traumatic brain injury is challenging. A hemoglobin-based oxygen carrier may offer advantages. The novel therapeutic carrier, polynitroxylated pegylated hemoglobin (PNPH), represent a neuroprotective for resuscitation. Hypotheses: 1) PNPH unique non-neurotoxic in neuronal culture and vitro models. 2) with would require less volume to restore mean arterial blood pressure than lactated Ringer's or Hextend confer neuroprotection mouse...
α-Synuclein is one of the most abundant proteins in presynaptic terminals. Normal expression α-synuclein essential for neuronal survival and it prevents initiation apoptosis neurons through covalent cross-linking cytochrome c released from mitochondria. Exocytosis occurs with mitochondrial dysfunction, making its detection cerebrospinal fluid (CSF) children after severe traumatic brain injury (TBI) a potentially important marker injury. Experimental therapeutic hypothermia (TH) improves...
Secondary insults, such as hemorrhagic shock (HS), worsen outcome from traumatic brain injury (TBI). Both TBI and HS modulate levels of inflammatory mediators. We evaluated the addition on response to TBI. Adult male C57BL6J mice were randomized into five groups (n=4 [naïve] or 8/group): naïve; sham; (through mild-to-moderate controlled cortical impact [CCI] at 5 m/sec, 1-mm depth), HS; CCI+HS. All non-naïve underwent identical monitoring anesthesia. CCI+HS a 35-min period...
Extracellular adenosine 3',5'-cyclic monophosphate (3',5'-cAMP) is an endogenous source of localized production in many organs. Recent studies suggest that extracellular 2',3'-cAMP (positional isomer 3',5'-cAMP) also a adenosine, particularly the brain vivo post-injury. Moreover, vitro show both microglia and astrocytes can convert to adenosine. Here, we examined ability primary mouse oligodendrocytes neurons metabolize their respective monophosphates (2'-AMP 3'-AMP). Cells were isolated...
Cerebral edema is critical to morbidity/mortality in traumatic brain injury (TBI) and worsened by hypotension. Glibenclamide may reduce cerebral inhibiting sulfonylurea receptor-1 (Sur1); its effect on diffuse exacerbated hypotension/resuscitation unknown. We aimed determine if glibenclamide improves pericontusional and/or controlled cortical impact (CCI) (5m/sec, 1 mm depth) plus hemorrhagic shock (HS) (35 min), compare effects CCI alone. C57BL/6 mice were divided into five groups (n =...
Objectives: Extracorporeal cardiopulmonary resuscitation with bypass potentially provides cerebral reperfusion, cardiovascular support, and temperature control for from cardiac arrest. We hypothesized that extracorporeal is feasible after ventricular fibrillation arrest in rats improves outcome versus conventional resuscitation. Design: Prospective randomized study. Setting: University laboratory. Subjects: Adult male Sprague-Dawley rats. Interventions: Rats (intubated, instrumented arterial...
Macrophages contribute to secondary damage and repair after central nervous system (CNS) injury. Micron-sized paramagnetic iron oxide (MPIO) particles can label macrophages in situ, facilitating three-dimensional (3D) mapping of macrophage accumulation following traumatic brain injury (TBI), via ex vivo magnetic resonance microscopy (MRM) monitoring with imaging (MRI). MPIO were injected intravenously (iv; 4.5 mg Fe/Kg) male C57BL/6J mice (n = 21). A controlled cortical impact (CCI) was...
Splicing factors (SFs) coordinate nuclear intron/exon splicing of RNA. factor disturbances can cause cell death. RNA binding motif 5 (RBM5) and 10 (RBM10) promote apoptosis in cancer cells by activating detrimental alternative key death/survival genes. The role(s) RBM5/10 neurons has not been established. Here, we report that RBM5 knockdown human neuronal decreases caspase activation staurosporine. In contrast, RBM10 augments activation. To determine whether brain injury alters RBM...
Introduction: Neuroinflammation plays a critical role in tissue injury and repair after neonatal hypoxic-ischemic (HI) brain varies by sex. Growth differentiation factor-15 (GDF-15) is cytokine released macrophages during inflammation upregulated ischemia. We examined the impact of GDF-15 knockout (KO) on volume loss combined microglia/macrophage response Rice Vannucci model HI injury. Methods: Male female wild-type (WT) Gdf15+/+, heterozygous Gdf15nuGFP-CE/+ (Het), homozygous...