Abstract:Structural changes in the brain of outbred mice were studied after infection with influenza A/H5N1 strain isolated in the Novosibirsk region. High mortality was observed after intranasal infection. Examination of brain specimens revealed vasculopathies with thrombosis of the microcirculatory vessels, pericellular and perivascular edema with multifocal ischemic necrosis, hyperplasia of glial cells, caspase-dependent apoptosis of neurons caused by the cytopathic effect of the virus, and hypercytokinemia.
“…Mice are also important models for human brains and frequently employed in morphometric assessments of brain pathology (among many others, Badea et al 2007;Chuang et al 2011;Johnson et al 2007;Ronald et al 2009;Sharief et al 2008;Potapova et al 2009). …”
Section: Animals and Dissectionmentioning
confidence: 99%
“…The introduction of fast virtual reconstruction techniques of mammalian brain morphology has lead to considerable advances in many fields of neuroscience, including medical research on humans (Dawe et al 2009;de Crespigny et al 2008;Grinberg et al 2008;Sun et al 2005;Yong-Hing et al 2005), model organisms (Ronald et al 2009;Saikali et al 2010;Potapova et al 2009), anthropological study (de Sousa et al 2010), and evolutionary investigations of mammalian brain size and -shape (e.g. Hakeem et al 2005;Montie et al 2007;Nieuwenhuys 2009).…”
Although morphometric studies of fixed mammalian brains are an integral part of neuroscience, the nature of fixation-related morphometric artifacts is not well understood beyond assessments of size changes over fixation time. This study is the first to quantitatively co-evaluate the effects of the most common brain tissue fixative--formalin--on brain shape, size, and weight, using two-dimensional landmark analysis of mouse brains fixed in unbuffered, non-saline formalin from fresh specimens up to 213 days of preservation. The brains show a typical swelling reaction with subsequent decline in size and weight. Weight initially under- and later over-estimates size, so that the practice of using weight to estimate volume can be problematic. Time to recovery of original size resembled that of much larger brained mammals, suggesting that the slow reaction of formalin with tissue components mainly determines recovery times. Non-size related (anisotropic) distortion of different brain areas accounted for around a quarter of overall change suggesting that the use of "all-brain" fixation correction factors can introduce considerable error. Distortion occurs mostly after the first day of fixation, and extended fixation times impact mostly on size, not shape. Fixation effects relatively wider and stouter brain dimensions, except the cerebellum whose shape changes less. Evidence from the literature suggests that this pattern may be common to mammals due to structural commonalities.
“…Mice are also important models for human brains and frequently employed in morphometric assessments of brain pathology (among many others, Badea et al 2007;Chuang et al 2011;Johnson et al 2007;Ronald et al 2009;Sharief et al 2008;Potapova et al 2009). …”
Section: Animals and Dissectionmentioning
confidence: 99%
“…The introduction of fast virtual reconstruction techniques of mammalian brain morphology has lead to considerable advances in many fields of neuroscience, including medical research on humans (Dawe et al 2009;de Crespigny et al 2008;Grinberg et al 2008;Sun et al 2005;Yong-Hing et al 2005), model organisms (Ronald et al 2009;Saikali et al 2010;Potapova et al 2009), anthropological study (de Sousa et al 2010), and evolutionary investigations of mammalian brain size and -shape (e.g. Hakeem et al 2005;Montie et al 2007;Nieuwenhuys 2009).…”
Although morphometric studies of fixed mammalian brains are an integral part of neuroscience, the nature of fixation-related morphometric artifacts is not well understood beyond assessments of size changes over fixation time. This study is the first to quantitatively co-evaluate the effects of the most common brain tissue fixative--formalin--on brain shape, size, and weight, using two-dimensional landmark analysis of mouse brains fixed in unbuffered, non-saline formalin from fresh specimens up to 213 days of preservation. The brains show a typical swelling reaction with subsequent decline in size and weight. Weight initially under- and later over-estimates size, so that the practice of using weight to estimate volume can be problematic. Time to recovery of original size resembled that of much larger brained mammals, suggesting that the slow reaction of formalin with tissue components mainly determines recovery times. Non-size related (anisotropic) distortion of different brain areas accounted for around a quarter of overall change suggesting that the use of "all-brain" fixation correction factors can introduce considerable error. Distortion occurs mostly after the first day of fixation, and extended fixation times impact mostly on size, not shape. Fixation effects relatively wider and stouter brain dimensions, except the cerebellum whose shape changes less. Evidence from the literature suggests that this pattern may be common to mammals due to structural commonalities.
“…By 10th d.p.i large areas of leukocyte infiltration in the cortex and local hemorrhage were also observed. In addition the neuronal nuclei had dark structures common to the cell nuclei disrupted by the virus [11]. As soon as we found some certain differences between the brain tissues of the infected and control groups we suggested that these disruptions can be related to the observed behavior signs.…”
Section: Resultsmentioning
confidence: 68%
“…We were able to observe neuropathological behavioral signs such as tremor and circular movements in mice infected with A/great crested grebe/Tyva/22/2010, a phenomenon not previously described for HPAI H5N1 viruses isolated in 2009. Affected mice were sacrificed and tissue samples were taken for morphological investigation as described by [11]. Numerous hemorrhages were detected in the internal organs.…”
Section: Resultsmentioning
confidence: 99%
“…Affected mice were sacrificed and tissue samples were taken for morphological investigation as described by Potapova et al [11].…”
An outbreak of the Highly Pathogenic Avian Influenza H5N1 (HPAI H5N1) was reported in wild birds in 2010. Three strains (A/black-headed gull/Tyva/8/2010, A/spoonbill/Tyva/1/2010, and A/great crested grebe/Tyva/22/2010) were isolated and studied by the virological and molecularbiological methods. Viruses shown to be highly pathogenic in chicken and mice. We found some disruptions in brain tissues that can be related to the observed neuropathological behavior signs in mice. Close antigenic relationship between the investigated strains and those isolated at the Uvs Nuur Lake in 2009 and in the Russian Far East in 2008 (both clade 2.3.2) were also shown. Phylogenetic analysis of the hemagglutinin gene revealed a close relation to the strains isolated during outbreaks at the same location in 2009, as well as at the Qinghai Lake in 2009, and in Mongolia in 2010; as all of them falling into clade 2.3.2. Early AIV detection in this area can play an important role in terms of outbreak prediction, early warning and isolating new AIV strains when they start spreading from Asia to Russia and Europe. Further investigation of the global distribution of clade 2.3.2 and 2.2 HPAI H5N1 viruses will prove to be invaluable for better understanding of the evolutionary ecology of avian influenza viruses.
Oxidized dextran is suggested for prevention of infection induced by influenza A/H5N1 viruses, methods of its use and doses are determined. Two intravenous injections of dextran 3 and 1 days before experimental infection of outbred mice by influenza A/H5N1 A/goose/Krasnoozerskoye/627/05 virus resulted in a high preventive dose-dependent effect: the mean lifespan was 25% prolonged, the mortality decreased 3-fold.
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