- Intracranial Aneurysms: Treatment and Complications
- Neuroinflammation and Neurodegeneration Mechanisms
- Adipose Tissue and Metabolism
- Vascular Malformations Diagnosis and Treatment
- Traumatic Brain Injury and Neurovascular Disturbances
- Intracerebral and Subarachnoid Hemorrhage Research
- Developmental Biology and Gene Regulation
- Mitochondrial Function and Pathology
- Cerebrospinal fluid and hydrocephalus
- RNA Research and Splicing
- Congenital heart defects research
- Neuroscience and Neuropharmacology Research
- Lipid metabolism and biosynthesis
- Axon Guidance and Neuronal Signaling
- Neurogenesis and neuroplasticity mechanisms
- Receptor Mechanisms and Signaling
- Vagus Nerve Stimulation Research
- ATP Synthase and ATPases Research
- Moyamoya disease diagnosis and treatment
- Connexins and lens biology
- Cerebrovascular and Carotid Artery Diseases
- Cell Image Analysis Techniques
- Acute Ischemic Stroke Management
- S100 Proteins and Annexins
- Advanced Fluorescence Microscopy Techniques
Neurological Surgery
2018-2024
University of Virginia
2019-2024
University of Virginia Health System
2018-2024
University of Utah
2008-2018
Howard Hughes Medical Institute
2004-2013
Stockholm University
1994-2005
Czech Academy of Sciences
1992
Czech Academy of Sciences, Institute of Physiology
1991-1992
Whereas the physiological significance of microsomal fatty acid elongation is generally appreciated, its molecular nature poorly understood. Here, we describe tissue-specific regulation a novel mouse gene family encoding components implicated in synthesis very long chain acids. The Ssc1 appears to be ubiquitously expressed, whereas Ssc2 and Cig30 show restricted expression pattern. Their translation products are all integral membrane proteins with five putative transmembrane domains. By...
Very little is known about the in vivo regulation of mammalian fatty acid chain elongation enzymes as well role specific length cellular responses and developmental processes. Here, we report that Elovl3 gene product, which belongs to a highly conserved family microsomal involved formation very long acids, revealed distinct expression skin was restricted sebaceous glands epithelial cells hair follicles. By disruption by homologous recombination mouse, show ELOVL3 participates neutral lipids...
ELOVL2 is a member of the mammalian microsomal ELOVL fatty acid enzyme family, involved in elongation very long-chain acids including PUFAs required for various cellular functions mammals. Here, we used ELOVL2-ablated (Elovl2(-/-)) mice to show that with 24-30 carbon atoms ω-6 family testis are indispensable normal sperm formation and fertility male mice. The lack Elovl2 was associated complete arrest spermatogenesis, seminiferous tubules displaying only spermatogonia primary spermatocytes...
During the recruitment process of brown adipose tissue, mRNA level fatty acyl chain elongase Elovl3 is elevated more than 200-fold in cold-stressed mice. We have obtained Elovl3-ablated mice and report here that, although cold-acclimated experienced an increased heat loss due to impaired skin barrier, they were unable hyperrecruit their tissue. Instead, used muscle shivering order maintain body temperature. Lack resulted a transient decrease capacity elongate saturated acyl-CoAs into very...
Microglia, the resident immune cells of brain parenchyma, are highly responsive to tissue injury. Following cell damage, microglial processes redirect their motility from randomly scouting extracellular space specifically reaching toward compromised tissue. While morphology aspects this defense mechanism have been characterized, intracellular events underlying these responses remain largely unknown. Specifically, role Ca(2+) dynamics has not systematically investigated in acutely activated...
Background Transplantation of autologous mitochondria into ischemic tissue may mitigate injury caused by ischemia and reperfusion. Methods Using murine stroke models middle cerebral artery occlusion, we sought to evaluate feasibility delivery viable brain parenchyma. We evaluated the effects concurrent focused ultrasound activation microbubbles, which serves open blood–brain barrier, on efficacy mitochondria. Results Following intraarterial delivery, distribute through stroked hemisphere...
We have identified a previously uncharacterized gene that is implicated in the thermogenic function of brown adipose tissue mice. This gene, termed Cig30, first mammalian member novel family comprising several nematode and yeast genes, such as SUR4 FEN1, mutation which associated with highly pleiotropic phenotypes. It codes for 30-kDa plasma membrane glycoprotein five putative transmembrane domains. The Cig30 mRNA was readily detected only fat liver. When animals were exposed to 3-day cold...
The physiological and neurological correlates of plummeting brain osmolality during edema, traumatic CNS injury, severe ischemia are compounded by neuroinflammation. Using multiple approaches, we investigated how retinal microglia respond to challenges mediated increases in strain, osmotic gradients, agonists the stretch-activated cation channel TRPV4. Dissociated intact were TRPV4-immunoreactive responded selective agonist GSK1016790A substrate stretch with altered motility elevations...
Ischemic injury triggers multiple pathological responses in the brain tissue, including spreading depolarizations across cerebral cortex (cortical [CSD]). Microglia have been recently shown to play a significant role propagation of CSD. However, intracellular myeloid cells during ischemic stroke not investigated.We studied calcium activity cortical microglia model middle artery occlusion, using murine Polr2a-based and Cre-dependent GCaMP5 tdTomato reporter (PC::G5-tdT). High-speed 2-photon...
A low content of mitochondrial ATPase in brown adipose tissue (BAT) has previously been found to contrast with high levels the transcripts β-subunit F1 part and encoded subunits (Houstek, J., Tvrdík, P., Pavelka, S., Baudysová, M.(1991) FEBS Lett. 294, 191-194). To delineate which subunit limits synthesis complex, we have studied expression nuclear genes encoding α, β, γ catalytic b, c, d, OSCP F0 ATPase.In comparison other tissues mice, α-F1, β-F1, γ-F1, b-F0, d-F0, were BAT. The only...
Formation of neuronal circuits in the head requires coordinated development neurons within central nervous system (CNS) and neural crest-derived peripheral target tissues. Hoxb1, which is expressed throughout rhombomere 4 (r4), has been shown to be required for specification facial branchiomotor neuron progenitors that are programmed innervate muscles expression. In this study, we have uncovered additional roles Hoxb1-expressing cells formation maintenance VIIth cranial nerve circuitry. By...
Complex interactions between networks of astrocytes and neurons are beginning to be appreciated, but remain poorly understood. Transgenic mice expressing fluorescent protein reporters cellular activity, such as the GCaMP family genetically encoded calcium indicators (GECIs), have been used explore network behavior. However, in some cases, it may desirable use long-established rat models that closely mimic particular aspects human conditions Parkinson's disease development epilepsy following...
Arteriovenous malformation (AVM) presenting with epilepsy significantly impacts patient quality of life, and it should be considered very much a seizure disorder. Although hemorrhage prevention is the primary treatment aim AVM surgery, control also at forefront therapeutic management. Several hemodynamic morphological characteristics have been identified to associated presentation. This includes increased flow, presence long pial draining vein, venous outflow obstruction, frontotemporal...
Aneurysmal subarachnoid hemorrhage (SAH) is associated with the development of delayed cognitive deficits. Neutrophil infiltration into central nervous system linked to these deficits after SAH. It however unclear how neutrophil activity influences function in The present project aims elucidate which factors mediate injury and SAH.Using a murine model SAH mice deficient effector functions, we determined critical In vivo vitro techniques were used investigate possible pathways neutrophils...