A5026199302- Neuroinflammation and Neurodegeneration Mechanisms
- Nerve injury and regeneration
- Neurogenesis and neuroplasticity mechanisms
- Blood Coagulation and Thrombosis Mechanisms
- S100 Proteins and Annexins
- Neuroscience of respiration and sleep
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Spinal Cord Injury Research
- Pain Mechanisms and Treatments
- Axon Guidance and Neuronal Signaling
- Musculoskeletal pain and rehabilitation
- Infant Health and Development
- Neurological Disease Mechanisms and Treatments
- Spine and Intervertebral Disc Pathology
- Gastrointestinal motility and disorders
- Control Systems and Identification
- Supramolecular Self-Assembly in Materials
- Extracellular vesicles in disease
- Cardiac Ischemia and Reperfusion
- Child Nutrition and Feeding Issues
- Advanced Scientific Research Methods
- Traumatic Brain Injury and Neurovascular Disturbances
- Gene Regulatory Network Analysis
- RNA Research and Splicing
- Ion Channels and Receptors
Cedars-Sinai Medical Center
2023-2024
Regenerative Medicine Institute
2023-2024
University of California, Los Angeles
2014-2023
Slovak Academy of Sciences
2021
Institute of Neurobiology
2021
Michigan State University
2007-2010
Significance Molecular mechanisms underlying distinct disabilities during neurological diseases may differ based on the pathway involved. Multiple sclerosis (MS) is multifocal, characterized by affecting walking, vision, cognition, and fatigue. Neuroprotective treatments tailored for each disability be more effective than nonspecific aiming to reduce a composite of in clinical trials. Here, we use MS model apply cell-specific region-specific gene expression approach discover targets...
Abstract Ependyma have been proposed as adult neural stem cells that provide the majority of newly proliferated scar-forming astrocytes protect tissue and function after spinal cord injury (SCI). This proposal was based on small, midline stab SCI. Here, we tested generality this by using a genetic knock-in cell fate mapping strategy in different murine SCI models. After large crush injuries across entire cord, ependyma-derived progeny remained local, did not migrate contributed few any kind...
Low back pain (LBP) is often associated with the degeneration of human intervertebral discs (IVDs). However, pain-inducing mechanism in degenerating remains to be elucidated. Here, we identified a subtype locally residing nucleus pulposus cells (NPCs), generated by certain conditions discs, that was onset discogenic pain. Single-cell transcriptomic analysis tissues showed strong correlation between specific cell and condition degenerated disc, suggesting they are pain-triggering. The...
Kallikrein 6 (KLK6) is a secreted serine protease preferentially expressed by oligodendroglia in CNS white matter. Elevated levels of KLK6 occur actively demyelinating multiple sclerosis (MS) lesions and cases spinal cord injury (SCI), stroke, glioblastoma. Taken with recent evidence establishing as CNS‐endogenous activator protease‐activated receptors (PARs), we hypothesized that activates subset PARs to regulate oligodendrocyte physiology potentially pathophysiology. Here, primary cultures...
Spared regions of the damaged central nervous system undergo dynamic remodeling and exhibit a remarkable potential for therapeutic exploitation. Here, lesion-remote astrocytes (LRAs), which interact with viable neurons, glia neural circuitry, reactive transformations whose molecular functional properties are poorly understood. Using multiple transcriptional profiling methods, we interrogated LRAs from spared mouse spinal cord following traumatic injury (SCI). We show that acquire spectrum...
Kallikrein-related peptidase 6 (KLK6) is a trypsin-like serine protease upregulated at sites of central nervous system (CNS) injury, including de novo expression by reactive astrocytes, yet its physiological actions are largely undefined. Taken with recent evidence that KLK6 activates G-protein-coupled protease-activated receptors (PARs), we hypothesized injury-induced elevations in contribute to the development astrogliosis and this occurs PAR-dependent fashion. Using primary murine...
Biomaterial vehicles have the potential to facilitate cell transplantation in central nervous system (CNS). We previously shown that highly tunable ionic diblock copolypeptide hydrogels (DCH) can provide sustained release of hydrophilic and hydrophobic molecules CNS. Here, we show recently developed nonionic thermoresponsive DCH, called DCHT, exhibit excellent cytocompatibility. Neural stem (NSC) suspensions DCHT were easily injected as liquids at room temperature. with a viscosity tuned...
Kallikreins (KLKs) are a family of 15 secreted serine proteases with emerging roles in neurologic diseases. To illuminate their contributions to the pathophysiology spinal cord injury (SCI), we evaluated acute through chronic changes immunohistochemical appearance 6 KLKs (KLK1, KLK5, KLK6, KLK7, KLK8, and KLK9) postmortem human traumatic SCI cases, quantified RNA expression levels experimental murine SCI, assessed impact recombinant forms each enzyme toward cortical neurons vitro. Temporally...
Inflammatory bowel diseases (IBD) can involve widespread gastrointestinal dysfunction, even in cases which inflammation is localized to a single site. The underlying pathophysiology of dysfunction noninflamed regions unclear. We examined whether colitis associated with altered electrogenic ion transport the ileal mucosa and/or changes properties submucosal neurons. Colitis was induced by administration trinitrobenzene sulfonic acid (TNBS), and uninflamed ileum from animals 3, 7, 28 days...
Inhibitory neurotransmission to the longitudinal muscle is more prominent in neonatal than adult guinea pig ileum.Inhibitory neuromuscular transmission was investigated using vitro ileal myenteric plexus (LMMP) preparations made from (< or =48 h postnatal) and ( approximately 4 weeks pigs.Amperometric measurements of nicotine-induced nitric oxide (NO) release (measured as an oxidation current) ganglia revealed larger currents (379 +/- 24 pA) vs (119 39 pA, P < 0.05) tissues. Nicotine-induced...
Abstract Neuromuscular transmission is crucial for normal gut motility but little known about its postnatal maturation. This study investigated excitatory/inhibitory neuromuscular in vitro using ileal nerve‐muscle preparations made from neonatal (≤48 h postnatal) and adult (∼4 months guinea pigs. In tissues neonates adults, nicotine (0.3–30 μmol L −1 ) contracted longitudinal muscle a tetrodotoxin (TTX) (0.3 )‐sensitive manner. The muscarinic receptor antagonist, scopolamine (1 ), reduced...
Abstract Low back pain (LBP) is often associated with the degeneration of human intervertebral discs (IVDs). However, pain-inducing mechanism in degenerating remains to be elucidated. Here, we identified a subtype locally residing nucleus pulposus cells (NPCs), generated by environmental stress discs, that triggered onset discogenic LBP. Single-cell transcriptomic analysis tissues showed strong correlation between this specific pain-triggering and conditions degenerated discs. Next,...