Biomedical subjects

Josef Priller

Publications and source records attributed to Josef Priller.

At least 19 recordsLinked to original sources

PubMed2026

Subjective cognition trajectories, Alzheimer biomarkers, and incident mild cognitive impairment.

BACKGROUND: Subjective cognitive decline is common in older adults and may represent an early clinical signal along the Alzheimer's disease continuum. The clinical relevance of longitudinal changes in subjective cognitive decline remains unclear. OBJECTIVES: To determine whether trajectories of self- or study partner-reported cognitive decline predict progression to mild cognitive impairment and reflect Alzheimer's disease-specific biological patterns. DESIGN, SETTING, PARTICIPANTS: Data were pooled from two observational cohorts. Cognitively unimpaired participants with baseline amyloid status, repeated assessments of subjective cognitive decline, and clinical follow-up were included. The study included 770 participants with a median follow-up of 5.0 years (interquartile range 4.0-7.0). MEASUREMENTS: Subjective cognitive decline was assessed using the Everyday Cognition questionnaire completed by participants and study partners. Linear mixed-effects models examined associations with amyloid status and progression to mild cognitive impairment. Cox proportional hazards models tested whether one-year changes predicted progression. RESULTS: Amyloid-positive participants and those who progressed to mild cognitive impairment showed steeper increases in self- and study partner-reported cognitive difficulties over time. Among amyloid-positive participants, only increases in study partner-report differentiated progressors from non-progressors. One-year increases in study partner-report predicted a higher risk of mild cognitive impairment compared with unchanged scores (hazard ratio 3.24; 95% confidence interval 1.73-6.07]), with effects confined to amyloid-positive participants. CONCLUSIONS: Short-term increases in study partner-reported cognitive difficulties identify amyloid-positive cognitively unimpaired older adults at increased risk of near-term progression to mild cognitive impairment. Longitudinal monitoring using study partner reports may provide a low-burden and clinically relevant approach for early risk stratification and surveillance in aging populations.

Humans↗

PubMed2025

A computational ontology framework for the synthesis of multi-level pathology reports from brain MRI scans.

BackgroundConvolutional neural network (CNN) based volumetry of MRI data can help differentiate Alzheimer's disease (AD) and the behavioral variant of frontotemporal dementia (bvFTD) as causes of cognitive decline and dementia. However, existing CNN-based MRI volumetry tools lack a structured hierarchical representation of brain anatomy, which would allow for aggregating regional pathological information and automated computational inference.ObjectiveDevelop a computational ontology pipeline for quantifying hierarchical pathological abnormalities and visualize summary charts for brain atrophy findings, aiding differential diagnosis.MethodsUsing FastSurfer, we segmented brain regions and measured volume and cortical thickness from MRI scans pooled across multiple cohorts (N = 3433; ADNI, AIBL, DELCODE, DESCRIBE, EDSD, and NIFD), including healthy controls, prodromal and clinical AD cases, and bvFTD cases. Employing the Web Ontology Language (OWL), we built a semantic model encoding hierarchical anatomical information. Additionally, we created summary visualizations based on sunburst plots for visual inspection of the information stored in the ontology.ResultsOur computational framework dynamically estimated and aggregated regional pathological deviations across different levels of neuroanatomy abstraction. The disease similarity index derived from the volumetric and cortical thickness deviations achieved an AUC of 0.88 for separating AD and bvFTD, which was also reflected by distinct atrophy profile visualizations.ConclusionsThe proposed automated pipeline facilitates visual comparison of atrophy profiles across various disease types and stages. It provides a generalizable computational framework for summarizing pathologic findings, potentially enhancing the physicians' ability to evaluate brain pathologies robustly and interpretably.

Humans↗

PubMed2006

Early and rapid engraftment of bone marrow-derived microglia in scrapie.

Prion neuroinvasion is accompanied by maximal activation of microglia, the significance of which for pathogenesis is unknown. Here, we used bone marrow (BM) cells expressing GFP (green fluorescent protein) to study the turnover of microglia in mouse scrapie. We found that >or=50% of all brain microglia were replaced by BM-derived cells before clinical disease onset. In terminally sick mice, microglia density increased threefold to fourfold. Hence BM-derived microglia rapidly and efficaciously colonize the brain in scrapie. Whereas reconstitution of wild-type mice with prion protein-deficient (Prnp(o/o)) BM did not alter scrapie pathogenesis, Prnp(o/o) mice transplanted with wild-type BM cells were resistant to peripherally administered prions despite high levels of infectivity in the spleen. Cerebellar homogenates from prion-inoculated Prnp(o/o) mice reconstituted with >10% of wild-type microglia failed to infect transgenic mice overexpressing the cellular prion protein. Hence, in contrast to previous reports, microglia are not competent for efficient prion transport and replication in vivo.

Animals↗

PubMed2006

Physical activity improves long-term stroke outcome via endothelial nitric oxide synthase-dependent augmentation of neovascularization and cerebral blood flow.

Physical activity upregulates endothelial nitric oxide synthase (eNOS), improves endothelium function, and protects from vascular disease. Here, we tested whether voluntary running would enhance neovascularization and long-term recovery following mild brain ischemia. Wild-type mice were exposed to 30 minutes of middle-cerebral artery occlusion (MCAo) and reperfusion. Continuous voluntary running on wheels conferred long-term upregulation of eNOS in the vasculature and of endothelial progenitor cells (EPCs) in the spleen and bone marrow (BM). This was associated with higher numbers of circulating EPCs in the blood and enhanced neovascularization. Moreover, engraftment of TIE2/LacZ-positive BM-derived cells was increased in the ischemic brain. Four weeks after the insult, trained animals showed higher numbers of newly generated cells in vascular sites, increased density of perfused microvessels and sustained augmentation of cerebral blood flow within the ischemic striatum. Moreover, running conferred tissue sparing and improved functional outcome at 4 weeks. The protective effects of running on angiogenesis and outcome were completely abolished when animals were treated with a NOS inhibitor or the antiangiogenic compound endostatin after brain ischemia, and in animals lacking eNOS expression. Voluntary physical activity improves long-term stroke outcome by eNOS-dependent mechanisms related to improved angiogenesis and cerebral blood flow.

Animals↗

PubMed2006

Roller culture of free-floating retinal slices: a new system of organotypic cultures of adult rat retina.

No experimental system exists to date for the in vitro study of retinal ganglion cell populations in a three-dimensional organotypic tissue environment. Here, we describe such a novel method for roller cultivation of adult retinas. Retinas of adult (1-3 months old) rats were cut into rectangular slices of approximately 1 mm(2). Free-floating slices were cultured on a horizontal rotating roller drum (50-60 rpm) in a dry incubator at 36.5 degrees C. During the first days of cultivation, primary flat retinal slices changed their configuration and transformed into ball-shaped tissue spheres (retinal bodies). Histological and immunocytochemical studies showed that the outer wall of the retinal bodies was formed by cell and fibre layers typical of mature retina with photoreceptors located on the outside. Initially, retinal bodies contained an inner cavity which later was completely obliterated and filled with glial cells, sprouting nerve fibres, and vascular structures. This culture system was further developed into a robust model of glutamate-induced neurotoxicity. Using a novel culture method of adult rat retina, preservation of the three-dimensional organotypic retinal cytoarchitecture was achieved, including survival of neurons in the ganglion cell layer and sprouting of nerve fibres of the axotomized retinal ganglion cells. This novel culture model promises to facilitate studies of retinal physiology and pathology.

Animals↗

PubMed2006

Circulating monocytes engraft in the brain, differentiate into microglia and contribute to the pathology following meningitis in mice.

Previous studies have demonstrated a potential role of brain endogenous microglia and meningeal macrophages in inflammation and brain injury during bacterial meningitis. However, the contribution of previously engrafted monocytes and microglia to this process is still unknown. We therefore used genetically labelled bone marrow-derived cells from transgenic mice expressing the green fluorescent protein (GFP) under the chicken beta-actin promoter to deliver fluorescently labelled monocytes to the diseased brain. Approximately 24 hours after Streptococcus pneumoniae infection, GFP-expressing parenchymal microglia changed their morphology to an activated phenotype and upregulated major histocompatibility complex class II molecules. Bacterial meningitis increased the engraftment of GFP+ monocytes and their differentiation to microglia during the post-inflammatory period, but not during acute meningitis. Importantly, these newly recruited monocytes became an integral part of the pool of parenchymal microglia and contributed to the clearance of damaged tissue by increased lysosomal activity and close location to apoptotic cells. Thus, circulating cells entering the brain such as monocytes/macrophages might provide a potential cellular target for the treatment of the tissue damage following meningitis via peripheral cell therapy.

Animals↗

PubMed2006

Improved reperfusion and neuroprotection by creatine in a mouse model of stroke.

Stroke leads to energy failure and subsequent neuronal cell loss. Creatine and phosphocreatine constitute a cellular energy buffering and transport system, and dietary creatine supplementation was shown to protect neurons in several models of neurodegeneration. Although creatine has recently been found to reduce infarct size after cerebral ischemia in mice, the mechanisms of neuroprotection remained unclear. We provide evidence for augmented cerebral blood flow (CBF) after stroke in creatine-treated mice using a magnetic resonance imaging (MRI)-based technique of CBF measurement (flow-sensitive alternating inversion recovery-MRI). Moreover, improved vasodilatory responses were detected in isolated middle cerebral arteries obtained from creatine-treated animals. After 3 weeks of dietary creatine supplementation, minor changes in brain creatine, phosphocreatine, adenosine triphosphate, adenosine diphosphate and adenosine monophosphate levels were detected, which did not reach statistical significance. However, we found a 40% reduction in infarct volume after transient focal cerebral ischemia. Our data suggest that creatine-mediated neuroprotection can occur independent of changes in the bioenergetic status of brain tissue, but may involve improved cerebrovascular function.

Adenosine Triphosphate↗

PubMed2005

Nitric oxide modulates calcium entry through P/Q-type calcium channels and N-methyl-d-aspartate receptors in rat cortical neurons.

Voltage-gated calcium channels (VGCC) and N-methyl-d-aspartate receptors (NMDAR) account for most of the depolarization-induced neuronal calcium entry. The susceptibility of individual routes of calcium entry for nitric oxide (NO) is largely unknown. We loaded cultured rat cortical neurons with fluo-4 acetoxymethylester to study the effect of the NO synthase inhibitor Nomega-nitro-l-arginine and the NO donor S-nitroso-N-acetylpenicillamine on the intracellular calcium concentration ([Ca2+]i). The potassium-induced [Ca2+]i increase was amplified by Nomega-nitro-l-arginine and attenuated by S-nitroso-N-acetylpenicillamine. This modulation was abolished by either the P/Q-type VGCC antagonist omega-agatoxin IVA or by the NMDAR antagonist MK-801, but not by N-type (omega-conotoxin GVIA) or L-type (nimodipine) VGCC blockers. These results suggest that NO can modulate neuronal calcium entry during depolarization by interacting with P/Q-type VGCC and NMDAR.

Action Potentials↗

PubMed2005

Circulating monocytic cells infiltrate layers of anterograde axonal degeneration where they transform into microglia.

In this study, we demonstrate the infiltration of blood-derived monocytic cells and their morphologic transformation into microglia in zones of acute, anterograde (Wallerian) axonal degeneration induced by entorhinal cortex lesion (ECL). ECL was performed in mice which had received green fluorescent protein (GFP)-transduced bone marrow grafts allowing identification of blood-derived elements within the brain. While in the unlesioned hemisphere GFP+ cells were restricted to perivascular and leptomeningeal sites, many round fluorescent cells appeared in hippocampal zones of axonal degeneration at 24 h post lesion (hpl). Within 72 hpl, these GFP+ cells acquired ramified, microglia-like morphologies, which persisted for at least 7 days post ECL. Differentiation of GFP+ cells into glial fibrillary acidic protein (GFAP)+ astrocytes was never observed. To exclude that this recruitment is an artifact of irradiation or bone marrow transplantation, the fluorescent cell tracker 6-carboxylfluorescein diacetate (CFDA) was injected into spleens of normal mice 1 day before ECL. Again, fluorescent cells appeared at the lesion site and along the layers of axonal degeneration at 48 hpl and CFDA+/MAC-1+, cells exhibited amoeboid and ramified morphologies. Thus, blood-derived cells infiltrate not only the site of mechanical lesion, but also the layers of anterograde axonal degeneration, where they readily transform into microglia-like elements. A role for infiltrating leukocytes in facilitating or modulating postlesional plasticity, e.g., by phagocytosis of growth-inhibiting myelin should now be considered. Moreover, monocytic cells may serve as vehicles to transport therapeutic substances such as neurotrophic factors or caspase inhibitors to zones of axonal degeneration.

Animals↗

PubMed2005

Experimental autoimmune encephalomyelitis repressed by microglial paralysis.

Although microglial activation occurs in inflammatory, degenerative and neoplastic central nervous system (CNS) disorders, its role in pathogenesis is unclear. We studied this question by generating CD11b-HSVTK transgenic mice, which express herpes simplex thymidine kinase in macrophages and microglia. Ganciclovir treatment of organotypic brain slice cultures derived from CD11b-HSVTK mice abolished microglial release of nitrite, proinflammatory cytokines and chemokines. Systemic ganciclovir administration to CD11b-HSVTK mice elicited hematopoietic toxicity, which was prevented by transfer of wild-type bone marrow. In bone marrow chimeras, ganciclovir blocked microglial activation in the facial nucleus upon axotomy and repressed the development of experimental autoimmune encephalomyelitis. We conclude that microglial paralysis inhibits the development and maintenance of inflammatory CNS lesions. The microglial compartment thus provides a potential therapeutic target in inflammatory CNS disorders. These results validate CD11b-HSVTK mice as a tool to study the impact of microglial activation on CNS diseases in vivo.

Animals↗

PubMed2003

Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation.

Infections are a leading cause of death in stroke patients. In a mouse model of focal cerebral ischemia, we tested the hypothesis that a stroke-induced immunodeficiency increases the susceptibility to bacterial infections. 3 d after ischemia, all animals developed spontaneous septicemia and pneumonia. Stroke induced an extensive apoptotic loss of lymphocytes and a shift from T helper cell (Th)1 to Th2 cytokine production. Adoptive transfer of T and natural killer cells from wild-type mice, but not from interferon (IFN)-gamma-deficient mice, or administration of IFN-gamma at day 1 after stroke greatly decreased the bacterial burden. Importantly, the defective IFN-gamma response and the occurrence of bacterial infections were prevented by blocking the sympathetic nervous system but not the hypothalamo-pituitary-adrenal axis. Furthermore, administration of the beta-adrenoreceptor blocker propranolol drastically reduced mortality after stroke. These data suggest that a catecholamine-mediated defect in early lymphocyte activation is the key factor in the impaired antibacterial immune response after stroke.

Animals↗

PubMed2003

Stress-induced dura vascular permeability does not develop in mast cell-deficient and neurokinin-1 receptor knockout mice.

Migraine headaches are often precipitated by stress and seem to involve neurogenic inflammation (NI) of the dura mater associated with the sensation of throbbing pain. Trigeminal nerve stimulation had been reported to activate rat dura mast cells and increase vascular permeability, effects inhibited by neonatal pretreatment with capsaicin implicating sensory neuropeptides, such as substance P (SP). The aim of the present study was to investigate NI, assessed by extravasation of 99-Technetium-gluceptate (99Tc-G), as well as the role of mast cells, SP and its receptor (NK-1R) in dura mater of mice in response to acute stress. Restraint stress for thirty min significantly increased 99Tc-G extravasation in the dura mater of C57BL mice. This effect was absent in W/W(v) mast cell-deficient mice and NK-1 receptor knockout mice (NK-1R-/-), but was unaltered in SP knockout mice (SP-/-). Acute restraint stress also resulted in increased dura mast cell activation in C57BL mice, but not in NK-1R-/- mice. These data demonstrate for the first time that acute stress triggers NI and mast cell activation in mouse dura mater through the activation of NK-1 receptors. The fact that SP-/- mice had intact vascular permeability response to stress indicates that some other NK-1 receptor agonist may substitute for SP. These results may help explain initial events in pathogenesis of stress-induced migraines.

Animals↗

PubMed2003

Robert Feulgen Prize Lecture. Grenzgänger: adult bone marrow cells populate the brain.

While the brain has traditionally been considered a rather secluded site, recent studies suggest that adult bone marrow (BM)-derived stem cells can generate glia and neurons in rodents and humans. Macrophages and microglia are the first to appear in the murine brain after transplantation of genetically marked BM cells. Within weeks after transplantation, some authors have found astrocytes and cells expressing neuronal antigens. We detected cerebellar Purkinje neurons and interneurons, such as basket cells, expressing the green fluorescent protein (GFP) 10-15 months after transplantation of GFP-labeled BM cells. The results push the boundaries of our classic view of lineage restriction.

Adult↗

PubMed2003

Estrogen increases bone marrow-derived endothelial progenitor cell production and diminishes neointima formation.

BACKGROUND: Estrogens improve endothelial function and accelerate reendothelialization after vascular injury via largely unknown mechanisms. Bone marrow-derived endothelial progenitor cells (EPCs) are thought to positively influence endothelialization, vascular repair, and angiogenesis. METHODS AND RESULTS: In mice subjected to sham operation, ovariectomy, or ovariectomy and estrogen replacement treatment, estrogen deficiency significantly decreased EPCs circulating in the peripheral blood and residing in the bone marrow, as well as EPCs that were in vitro expanded from spleen-derived mononuclear cells. These effects were completely prevented by estrogen replacement. Human women with increased estrogen plasma concentrations also displayed profoundly increased levels of circulating EPCs. Estrogens increase EPC numbers through a decreased apoptosis rate, which is mediated via a caspase-8-dependent pathway. Estrogen deficiency increased neointima formation after carotid artery injury in mice, but this effect was diminished by estrogen replacement therapy. In mice transplanted with green fluorescent protein-positive bone marrow, reendothelialization of injured vessel segments by bone marrow-derived cells was decreased during estrogen deficiency and increased in response to estrogen treatment. CONCLUSIONS: Estrogens increase numbers of EPCs by antiapoptotic effects leading to accelerated vascular repair and decreased neointima formation.

Animals↗

PubMed2003

Bone marrow-derived cells expressing green fluorescent protein under the control of the glial fibrillary acidic protein promoter do not differentiate into astrocytes in vitro and in vivo.

Differentiation of bone marrow (BM) cells into astroglia expressing the glial fibrillary acidic protein (GFAP) has been reported in vitro and after intracerebral or systemic BM transplantation. In contrast, recent data suggest that astrocytic differentiation does not occur from BM-derived cells in vivo. Using transgenic mice that express the enhanced green fluorescent protein (GFP) under the control of the human glial fibrillary acidic protein (GFAP) promoter, we investigated the potential of adult murine BM-derived cells to differentiate into macroglia. In the brains of GFAP-GFP transgenic mice, astrocytes were brightly fluorescent from the expression of GFP. When BM from these animals was transplanted into lethally irradiated wild-type animals, the transgene was detected in the reconstituted hematopoietic system, but no GFP expression was found in the nervous system. In contrast, GFAP-GFP neuroectodermal anlage grafted into adult wild-type striatum gave rise to GFP-expressing astrocytes. Because cerebral ischemia has been suggested to promote the differentiation of BM-derived cells into astrocytes, BM chimeric mice were subjected to focal cerebral ischemia. No GFP-positive cells were found in the ischemic or contralateral hemispheres of these brains. Even after direct injection of GFAP-GFP transgenic BM cells into wild-type striatum, no GFP-expressing astroglia were detected. To test the hypothesis that the in vitro environment might be more permissible for astroglial differentiation, we cultured BM from mice that constitutively express GFP, BM cells expressing GFP from a retroviral vector, and BM from GFAP-GFP transgenic mice on astrocytes and on organotypic hippocampal slices. In all experimental paradigms, BM-derived cells were found to differentiate into ramified microglia but not into GFAP-expressing astrocytes.

Animals↗

PubMed2002

Erythropoietin is a paracrine mediator of ischemic tolerance in the brain: evidence from an in vitro model.

In an in vitro model of cerebral ischemia (oxygen glucose deprivation, OGD) we investigated whether erythropoietin (EPO) plays a critical role in ischemic preconditioning. We found that EPO time and dose-dependently induced protection against OGD in rat primary cortical neurons. Protection was significant at 5 min and reached a maximum at 48 hr after EPO application. Protection was blocked by the coapplication of a soluble Epo receptor (sEpoR) or an antibody against EpoR (anti-EpoR). Medium transfer from OGD-treated astrocytes to untreated neurons induced protection against OGD in neurons, which was attenuated strongly by the application of sEpoR and anti-EpoR. In contrast, medium transfer from OGD-treated neurons to untreated neurons induced protection against OGD that did not involve EPO. In astrocytes the OGD enhanced the nuclear translocation of hypoxia-inducible factor 1 (HIF-1), the major transcription factor regulating EPO expression. Consequently, transcription of EPO-mRNA was increased in astrocytes after OGD. Cultured neurons express EpoR, and the Janus kinase-2 (JAK-2) inhibitor AG490 abolished EPO-induced tolerance against OGD. Furthermore, EPO-induced neuroprotection as well as phosphorylation of the proapoptotic Bcl family member Bad was reduced by the phosphoinositide-3 kinase (PI3K) inhibitor LY294002. The results suggest that astrocytes challenged with OGD provide paracrine protective signals to neurons. We provide evidence for the following signaling cascade: HIF-1 is activated rapidly by hypoxia in astrocytes. After HIF-1 activation the astrocytes express and release EPO. EPO activates the neuronal EPO receptor and, subsequently, JAK-2 and thereby PI3K. PI3K deactivates BAD via Akt-mediated phosphorylation and thus may inhibit hypoxia-induced apoptosis in neurons. Our results establish EPO as an important paracrine neuroprotective mediator of ischemic preconditioning.

Animals↗

PubMed2002

Bone marrow-derived progenitor cells modulate vascular reendothelialization and neointimal formation: effect of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition.

OBJECTIVE: Atherosclerosis and restenosis after vascular injury are both characterized by endothelial dysfunction, apoptosis, inappropriate endothelialization, and neointimal formation. Bone marrow-derived endothelial progenitor cells have been implicated in neovascularization, resulting in adult blood vessel formation. Despite the anticipated stem cell plasticity, the role of bone marrow-derived endothelial progenitor cells has not been clarified in vascular lesion development. METHODS AND RESULTS: We investigated vascular lesion formation in mice after transplantation of bone marrow transfected by means of retrovirus with enhanced green fluorescent protein. Carotid artery injury was induced, resulting in neointimal formation. Fluorescence microscopy and immunohistological analysis revealed that bone marrow-derived progenitor cells are involved in reendothelialization of the vascular lesions. Treatment with rosuvastatin (20 mg/kg body wt per day), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, enhanced the circulating pool of endothelial progenitor cells, propagated the advent of bone marrow-derived endothelial cells in the injured vessel wall, and, thereby, accelerated reendothelialization and significantly decreased neointimal formation. CONCLUSIONS: Vascular lesion development initiated by endothelial cell damage is moderated by bone marrow-derived progenitor cells. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibition promotes bone marrow-dependent reendothelialization and diminishes vascular lesion development. These findings may help to establish novel pathophysiological concepts and therapeutic strategies in the treatment of various cardiovascular diseases.

Animals↗

PubMed2002

Serial analysis of gene expression identifies metallothionein-II as major neuroprotective gene in mouse focal cerebral ischemia.

We applied serial analysis of gene expression (SAGE) to study differentially expressed genes in mouse brain 14 hr after the induction of focal cerebral ischemia. Analysis of >60,000 transcripts revealed 83 upregulated and 94 downregulated transcripts (more than or equal to eightfold). Reproducibility was demonstrated by performing SAGE in duplicate on the same starting material. Metallothionein-II (MT-II) was the most significantly upregulated transcript in the ischemic hemisphere. MT-I and MT-II are assumed to be induced by metals, glucocorticoids, and inflammatory signals in a coordinated manner, yet their function remains elusive. Upregulation of both MT-I and MT-II was confirmed by Northern blotting. MT-I and MT-II mRNA expression increased as early as 2 hr after 2 hr of transient ischemia, with a maximum after 16 hr. Western blotting and immunohistochemistry revealed MT-I/-II upregulation in the ischemic hemisphere, whereas double labeling demonstrated the colocalization of MT with markers for astrocytes as well as for monocytes/macrophages. MT-I- and MT-II-deficient mice developed approximately threefold larger infarcts than wild-type mice and a significantly worse neurological outcome. For the first time we make available a comprehensive data set on brain ischemic gene expression and underscore the important protective role of metallothioneins in ischemic damage of the brain. Our results demonstrate the usefulness of SAGE to screen functionally relevant genes and the power of knock-out models in linking function to expression data generated by high throughput techniques.

Animals↗