A5023740607- Neuroinflammation and Neurodegeneration Mechanisms
- Neonatal Respiratory Health Research
- Cell Adhesion Molecules Research
- Blood properties and coagulation
- Pregnancy and Medication Impact
- Infant Development and Preterm Care
- Barrier Structure and Function Studies
- Multiple Sclerosis Research Studies
- Neurogenesis and neuroplasticity mechanisms
- Neonatal and fetal brain pathology
- Neuroscience and Neuropharmacology Research
- Adolescent and Pediatric Healthcare
- Acute Ischemic Stroke Management
- Maternal Mental Health During Pregnancy and Postpartum
- Intracranial Aneurysms: Treatment and Complications
- Fetal and Pediatric Neurological Disorders
- Intracerebral and Subarachnoid Hemorrhage Research
- Axon Guidance and Neuronal Signaling
- Emergency and Acute Care Studies
- Extracellular vesicles in disease
- Inflammation biomarkers and pathways
- Ferroptosis and cancer prognosis
- Kruppel-like factors research
- Atherosclerosis and Cardiovascular Diseases
- Tryptophan and brain disorders
University of California, San Francisco
2012-2024
Gladstone Institutes
2012-2024
University of Iowa
2004
Blood-brain barrier disruption, microglial activation and neurodegeneration are hallmarks of multiple sclerosis. However, the initial triggers that activate innate immune responses their role in axonal damage remain unknown. Here we show blood protein fibrinogen induces rapid toward vasculature is required for neuroinflammation. Using vivo two-photon microscopy, demonstrate microglia form perivascular clusters before myelin loss or paralysis onset that, plasma proteins, specifically...
Abstract Autoimmunity and macrophage recruitment into the central nervous system (CNS) are critical determinants of neuroinflammatory diseases. However, mechanisms that drive immunological responses targeted to CNS remain largely unknown. Here we show fibrinogen, a blood coagulation protein deposited in after blood–brain barrier disruption, induces encephalitogenic adaptive immune peripheral leading demyelination. Fibrinogen stimulates unique transcriptional signature CD11b +...
Abstract Life-threatening thrombotic events and neurological symptoms are prevalent in COVID-19 persistent patients with long COVID experiencing post-acute sequelae of SARS-CoV-2 infection 1–4 . Despite the clinical evidence 1,5–7 , underlying mechanisms coagulopathy its consequences inflammation neuropathology remain poorly understood treatment options insufficient. Fibrinogen, central structural component blood clots, is abundantly deposited lungs brains COVID-19, correlates disease...
Abstract We used two‐channel three‐dimensional time‐lapse fluorescence confocal imaging in live rat hippocampal slice cultures (1–7 days vitro) to determine the motility behaviors of activated microglia as they engage dead and dying cells following traumatic brain tissue injury. Live were labeled with a fluorescently conjugated lectin (IB 4 ), neurons membrane‐impermeant fluorescent DNA‐binding dye (Sytox Orange or To‐Pro‐3). Tissue injury during slicing procedure induced neuronal death...
Although multiple sclerosis (MS) has been associated with the coagulation system, temporal and spatial regulation of activity in neuroinflammatory lesions is unknown. Using a novel molecular probe, we characterized pattern thrombin, central protease cascade, experimental autoimmune encephalomyelitis. Thrombin preceded onset neurological signs, increased at disease peak, correlated fibrin deposition, microglial activation, demyelination, axonal damage, clinical severity. Mice genetic deficit...
Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system. Although it has been extensively studied, proximate trigger immune response remains uncertain. Experimental autoimmune encephalomyelitis in common marmoset recapitulates many radiological and pathological features focal multiple lesions cerebral white matter, unlike traditional experimental rodents. This provides opportunity to investigate how form as well relative timing factors involved lesion...
Extrinsic inhibitors at sites of blood-brain barrier disruption and neurovascular damage contribute to remyelination failure in neurological diseases. However, therapies overcome the extrinsic inhibition are not widely available dynamics glial progenitor niche remodelling dysfunction largely unknown. By integrating vivo two-photon imaging co-registered with electron microscopy transcriptomics chronic neuroinflammatory lesions, we found that oligodendrocyte precursor cells clustered...
Cerebellar injury in preterm infants with central nervous system (CNS) hemorrhage results lasting neurological deficits and an increased risk of autism. The impact blood-induced pathways on cerebellar development remains largely unknown, so no specific treatments have been developed to counteract the harmful effects blood after neurovascular damage infants. Here, we show that fibrinogen, a blood-clotting protein, plays role impairing neonatal development. Longitudinal MRI revealed bleeds...
Abstract Objective To characterize the biochemical and demographic profiles of pregnant people with maternal immune activation (MIA) identify prenatal characteristics associated neurologic morbidity in offspring. Study design: This was a population-based retrospective cohort study mother-infant dyads births between 2009–2010 California. Multivariable logistic regression used to build MIA vulnerability profile including mid-pregnancy markers characteristics, its relationship infant examined....
Abstract Objective To characterize the biochemical and demographic profiles of pregnant people with maternal immune activation (MIA) identify prenatal characteristics associated neurologic morbidity in offspring. Study design This was a retrospective cohort study 602 mother-infant dyads births between 2009 2010 California. Multivariable logistic regression used to build MIA vulnerability profile including mid-pregnancy markers characteristics, its relationship infant examined. Results Of...