A5088801325- Neuroinflammation and Neurodegeneration Mechanisms
- Spinal Cord Injury Research
- Nerve injury and regeneration
- Neurogenesis and neuroplasticity mechanisms
- Immune Response and Inflammation
- Olfactory and Sensory Function Studies
- Immune cells in cancer
- Spinal Dysraphism and Malformations
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- Complement system in diseases
- Advanced Neuroimaging Techniques and Applications
- Chemokine receptors and signaling
- Axon Guidance and Neuronal Signaling
- Neonatal and fetal brain pathology
- Advanced MRI Techniques and Applications
- Single-cell and spatial transcriptomics
- Nerve Injury and Rehabilitation
- Pain Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Neurogenetic and Muscular Disorders Research
- Gene expression and cancer classification
- Multiple Sclerosis Research Studies
- Immunotherapy and Immune Responses
- Traumatic Brain Injury and Neurovascular Disturbances
The University of Queensland
2015-2025
Queensland Health
2015-2023
Allen Institute for Brain Science
2012-2013
The University of Western Australia
2003-2010
Monash University
2010
Lions Eye Institute
2010
Harry Perkins Institute of Medical Research
2003-2008
Netherlands Institute for Neuroscience
1999-2004
ABSTRACT Spatial Transcriptomics is an emerging technology that adds spatial dimensionality and tissue morphology to the genome-wide transcriptional profile of cells in undissociated tissue. Integrating these three types data creates a vast potential for deciphering novel biology cell their native morphological context. Here we developed innovative integrative analysis approaches utilise all first find types, then reconstruct type evolution within tissue, search regions with high...
Exercise has been shown to positively augment adult hippocampal neurogenesis; however, the cellular and molecular pathways mediating this effect remain largely unknown. Previous studies have suggested that microglia may ability differentially instruct neurogenesis in brain. Here, we used transgenic Csf1r-GFP mice investigate whether directly influence activation of neural precursor cells. Our results revealed an exercise-induced increase cell activity was mediated via endogenous abolished...
Spatial transcriptomics (ST) technologies generate multiple data types from biological samples, namely gene expression, physical distance between points, and/or tissue morphology. Here we developed three computational-statistical algorithms that integrate all to advance understanding of cellular processes. First, present a spatial graph-based method, pseudo-time-space (PSTS), model and uncover relationships transcriptional states cells across tissues undergoing dynamic change (e.g....
C3a is a key complement activation fragment, yet its neutrophil-expressed receptor (C3aR) still has no clearly defined role. In this study, we used neutrophil-dependent mouse model of intestinal ischemia-reperfusion (IR) injury to explore the role C3aR in acute tissue injuries. deficiency worsened injury, which corresponded with increased numbers tissue-infiltrating neutrophils. Circulating neutrophils were significantly −/− mice after ischemia, and also mobilized more circulating...
It is now widely accepted that hippocampal neurogenesis underpins critical cognitive functions, such as learning and memory. To assess the behavioral importance of adult-born neurons, we developed a novel knock-in mouse model allowed us to specifically reversibly ablate neurons at an immature stage. In these mice, diphtheria toxin receptor (DTR) expressed under control doublecortin (DCX) promoter, which allows for specific ablation DCX-expressing after administration while leaving neural...
The mouse dura mater, pia and choroid plexus contain resident macrophages dendritic cells (DCs). These participate in immune surveillance, phagocytosis of cellular debris, uptake antigens from the surrounding cerebrospinal fluid regulation many pathologic processes. We used Cx3cr1gfp knock-in, CD11c-eYFP transgenic bone marrow chimeric mice to characterize phenotype, density replenishment rate monocyte-derived meninges assess role chemokine receptor CX3CR1 on their number tissue...
In the CNS, no pathway dedicated to immune surveillance has been characterized for preventing anti-CNS responses that develop in autoimmune neuroinflammatory disease. Here, we identified a cells traffic from brain is associated with rostral migratory stream (RMS), which forebrain source of newly generated neurons. Evaluation fluorescently labeled leukocyte migration mice revealed DCs travel via RMS CNS cervical LNs (CxLNs), where they present antigen T cells. Pharmacologic interruption cell...
This study investigated the role of complement activation fragment C5a in secondary pathology following contusive spinal cord injury (SCI). C5ar(-/-) mice, which lack signaling receptor for C5a, displayed signs improved locomotor recovery and reduced inflammation during first week SCI compared with wild-type mice. Intriguingly, early mice deteriorated from day 14 onward, absence C5aR ultimately leading to poorer functional outcomes, larger lesion volumes, myelin content, more widespread at...
After experimental nerve injuries that extensively disrupt axons, such as chronic constriction injury, immune cells invade the nerve, related dorsal root ganglia (DRGs), and spinal cord, leading to hyperexcitability, raised sensitivity, pain. Entrapment neuropathies, carpal tunnel syndrome, involve minimal axon damage, but patients often report widespread symptoms. To understand underlying pathology, a tube was placed around sciatic in 8-week-old rats, progressive mild compression animals...
The present study uniquely combines olfactory ensheathing glia (OEG) implantation with <i>ex vivo</i> adenoviral (AdV) vector-based neurotrophin gene therapy in an attempt to enhance regeneration after cervical spinal cord injury. Primary OEG were transduced AdV vectors encoding rat brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or bacterial marker protein β-galactosidase (<i>LacZ</i>) and subsequently implanted into adult Fischer rats directly unilateral transection of the...
Adenoviral (AdV) vectors encoding neurotrophin-3 (AdV-NT-3) or the bacterial marker enzyme β-galactosidase (LacZ gene) were used to transduce olfactory ensheathing glia (OEG) cultures. AdV vector-transduced OEG expressed high levels of recombinant neurotrophin as shown by in situ hybridization and enzyme-linked immunosorbent assay techniques. The biological activity vector-derived NT-3 was determined a dorsal root ganglia neurite outgrowth assay. Engineered cell suspensions then injected...
Amyotrophic lateral sclerosis (ALS) is a fatal and rapidly progressing motor neuron disease without effective treatment. The complement system up-regulated in ALS, with recent studies indicating that the activation product C5a accelerates progression via C5a1 receptor (C5aR1). We therefore examined therapeutic effect of antagonism hSOD1G93A mice, most widely used preclinical model ALS.The selective orally active antagonist, PMX205, was administered to mice drinking water, both pre-...