scholarly journals In Vivo Imaging of Cerebral Microvascular Plasticity from Birth to Death

2012 ◽  
Vol 33 (1) ◽  
pp. 146-156 ◽  
Author(s):  
Roa Harb ◽  
Christina Whiteus ◽  
Catarina Freitas ◽  
Jaime Grutzendler
Keyword(s):  
Large Scale ◽  
Time Lapse ◽  
Confocal Imaging ◽  
Adult Brain ◽  
Vessel Formation ◽  
Adult Mice ◽  
Age Related ◽  
Vascular Stability

Cerebral function and viability are critically dependent on efficient delivery of oxygen and glucose through the microvasculature. Here, we studied individual microvessels in the intact brain using high-resolution confocal imaging and long-term time-lapse two-photon microscopy across the lifetime of a mouse. In the first postnatal month, we found large-scale sprouting but to our surprise the majority of sprouts underwent pruning and only a small fraction became perfused capillaries. After the first month, microvessel formation and elimination decreased and the net number of vessels stabilized. Although vascular stability was the hallmark of the adult brain, some vessel formation and elimination continued throughout life. In young adult mice, vessel formation was markedly increased after exposure to hypoxia; however, upon return to normoxia, no vessel elimination was observed, suggesting that new vessels constitute a long-term adaptive response to metabolic challenges. This plasticity was markedly reduced in older adults and aging where hypoxia-induced angiogenesis was absent. Our study describes, for the first time in vivo patterns of cerebral microvascular remodeling throughout life. Disruption of the observed balance between baseline turnover and vascular stability may underlie a variety of developmental and age-related degenerative neurological disorders.

An Improved In Vivo Rat Tail Vertebra Model for the Study of Trabecular Bone Adaptation

1999 ◽  
Author(s):  
Mark J. Eichler ◽  
Chi Hyun Kim ◽  
X. Edward Guo
Keyword(s):  
Trabecular Bone ◽  
Large Scale ◽  
Bone Fractures ◽  
Mechanical Load ◽  
Bone Adaptation ◽  
Surgical Trauma ◽  
Micro Computed Tomography ◽  
Age Related ◽  
Rat Tail

Abstract The role of mechanical loading in trabecular bone adaptation is important for the understanding of bone integrity in different loading scenarios such as microgravity and for the etiology of age-related bone fractures. There have been numerous in vivo animal studies of bone adaptation, most of which are related to cortical bone remodeling, aimed at the investigation of Wolff’s Law [4], An interesting experimental model for trabecular bone adaptation has been developed in the rat tail vertebrae [2,3]. This model is attractive for trabecular bone adaptation studies because a controlled mechanical load can be applied to a whole vertebra with minimal surgical trauma, using a relatively inexpensive animal model. In addition, with advanced micro computed tomography (micro-CT) or micro magnetic resonance imaging (micro-MRI) coupled with large scale finite element modeling techniques, it is possible to characterize the three-dimensional (3D) stress/strain environment in the bone tissue close to a cellular level (∼25μm) [1]. Therefore, this in vivo rat tail model has a tremendous potential for quantification of the relationship between mechanical stimulation and biological response in trabecular bone adaptation.

Bistability of somatic pattern memories: stochastic outcomes in bioelectric circuits underlying regeneration

2021 ◽  
Vol 376 (1821) ◽  
pp. 20190765 ◽  
Author(s):  
Giovanni Pezzulo ◽  
Joshua LaPalme ◽  
Fallon Durant ◽  
Michael Levin
Keyword(s):  
Large Scale ◽  
Computational Models ◽  
State Of The Art ◽  
Memory Representation ◽  
Theme Issue ◽  
Evolutionary Innovation ◽  
New Interpretation ◽  
The Brain

Nervous systems’ computational abilities are an evolutionary innovation, specializing and speed-optimizing ancient biophysical dynamics. Bioelectric signalling originated in cells' communication with the outside world and with each other, enabling cooperation towards adaptive construction and repair of multicellular bodies. Here, we review the emerging field of developmental bioelectricity, which links the field of basal cognition to state-of-the-art questions in regenerative medicine, synthetic bioengineering and even artificial intelligence. One of the predictions of this view is that regeneration and regulative development can restore correct large-scale anatomies from diverse starting states because, like the brain, they exploit bioelectric encoding of distributed goal states—in this case, pattern memories. We propose a new interpretation of recent stochastic regenerative phenotypes in planaria, by appealing to computational models of memory representation and processing in the brain. Moreover, we discuss novel findings showing that bioelectric changes induced in planaria can be stored in tissue for over a week, thus revealing that somatic bioelectric circuits in vivo can implement a long-term, re-writable memory medium. A consideration of the mechanisms, evolution and functionality of basal cognition makes novel predictions and provides an integrative perspective on the evolution, physiology and biomedicine of information processing in vivo . This article is part of the theme issue ‘Basal cognition: multicellularity, neurons and the cognitive lens’.

The Successful Long-Term Treatment of Age Related Erectile Dysfunction with hSlo cDNA in Rats In Vivo

2003 ◽  
Vol 170 (1) ◽  
pp. 285-290 ◽  
Author(s):  
A. MELMAN ◽  
W. ZHAO ◽  
K.P. DAVIES ◽  
R. BAKAL ◽  
G.J. CHRIST
Keyword(s):  
Erectile Dysfunction ◽  
Term Treatment ◽  
Age Related ◽  
Long Term Treatment

scholarly journals Large-Scale Chronically Implantable Precision Motorized Microdrive Array for Freely Behaving Animals

2008 ◽  
Vol 100 (4) ◽  
pp. 2430-2440 ◽  
Author(s):  
Jun Yamamoto ◽  
Matthew A. Wilson
Keyword(s):  
Single Unit ◽  
Large Scale ◽  
Neural Circuits ◽  
Brain Regions ◽  
Unit Recording ◽  
Chronic Recording ◽  
Large Numbers ◽  
Freely Behaving

Multiple single-unit recording has become one of the most powerful in vivo electro-physiological techniques for studying neural circuits. The demand has been increasing for small and lightweight chronic recording devices that allow fine adjustments to be made over large numbers of electrodes across multiple brain regions. To achieve this, we developed precision motorized microdrive arrays that use a novel motor multiplexing headstage to dramatically reduce wiring while preserving precision of the microdrive control. Versions of the microdrive array were chronically implanted on both rats (21 microdrives) and mice (7 microdrives), and relatively long-term recordings were taken.

scholarly journals Widespread promoter methylation of synaptic plasticity genes in long-term potentiation in the adult brain in vivo

BMC Genomics ◽  
2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Jesper L. V. Maag ◽  
Dominik C. Kaczorowski ◽  
Debabrata Panja ◽  
Timothy J. Peters ◽  
Clive R. Bramham ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Promoter Methylation ◽  
Long Term Potentiation ◽  
Adult Brain ◽  
Term Potentiation

scholarly journals SIRT1 is dispensable for function of hematopoietic stem cells in adult mice

Blood ◽  
2012 ◽  
Vol 119 (8) ◽  
pp. 1856-1860 ◽  
Author(s):  
Vid Leko ◽  
Barbara Varnum-Finney ◽  
Hongzhe Li ◽  
Yansong Gu ◽  
David Flowers ◽  
...  
Keyword(s):  
Wild Type Littermate ◽  
Hematopoietic Stem ◽  
Adult Mice ◽  
Transplantation Experiments ◽  
Lineage Distribution ◽  
Serial Transplantation ◽  
Rule Out

Abstract SIRT1 is an NAD+-dependent histone deacetylase implicated in the establishment of the primitive hematopoietic system during mouse embryonic development. However, investigation of the role of SIRT1 in adult hematopoiesis has been complicated by the high perinatal mortality of SIRT1-deficient mice (SIRT1−/−). We performed a comprehensive in vivo study of the hematopoietic stem cell (HSC) compartment in adult SIRT1−/− mice and show that, apart from anemia and leukocytosis in older mice, the production of mature blood cells, lineage distribution within hematopoietic organs, and frequencies of the most primitive HSC populations are comparable to those of wild-type littermate controls. Furthermore, we show that SIRT1-deficient BM cells confer stable long-term reconstitution in competitive repopulation and serial transplantation experiments. The results of the present study rule out an essential physiologic role for cell-autonomous SIRT1 signaling in the maintenance of the adult HSC compartment in mice.

scholarly journals Long-term in vivo time-lapse imaging of synapse development and plasticity in the cerebellum

2014 ◽  
Vol 111 (1) ◽  
pp. 208-216 ◽  
Author(s):  
Naoko Nishiyama ◽  
Jeremy Colonna ◽  
Elise Shen ◽  
Jennifer Carrillo ◽  
Hiroshi Nishiyama
Keyword(s):  
In Vivo Imaging ◽  
Time Window ◽  
Time Lapse ◽  
Mammalian Brain ◽  
Cerebellar Neurons ◽  
Brain Functions ◽  
Time Lapse Imaging ◽  
Synaptic Circuitry

Synapses are continuously formed and eliminated throughout life in the mammalian brain, and emerging evidence suggests that this structural plasticity underlies experience-dependent changes of brain functions such as learning and long-term memory formation. However, it is generally difficult to understand how the rewiring of synaptic circuitry observed in vivo eventually relates to changes in animal's behavior. This is because afferent/efferent connections and local synaptic circuitries are very complicated in most brain regions, hence it is largely unclear how sensorimotor information is conveyed, integrated, and processed through a brain region that is imaged. The cerebellar cortex provides a particularly useful model to challenge this problem because of its simple and well-defined synaptic circuitry. However, owing to the technical difficulty of chronic in vivo imaging in the cerebellum, it remains unclear how cerebellar neurons dynamically change their structures over a long period of time. Here, we showed that the commonly used method for neocortical in vivo imaging was not ideal for long-term imaging of cerebellar neurons, but simple optimization of the procedure significantly improved the success rate and the maximum time window of chronic imaging. The optimized method can be used in both neonatal and adult mice and allows time-lapse imaging of cerebellar neurons for more than 5 mo in ∼80% of animals. This method allows vital observation of dynamic cellular processes such as developmental refinement of synaptic circuitry as well as long-term changes of neuronal structures in adult cerebellum under longitudinal behavioral manipulations.

scholarly journals Rapid disruption of the cortical microcirculation after mild traumatic brain injury

2019 ◽  
Author(s):  
Ellen D. Witkowski ◽  
Şefik Evren Erdener ◽  
Kıvılcım Kılıç ◽  
Sreekanth Kura ◽  
Jianbo Tang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Vascular Dysfunction ◽  
Metabolic Stress ◽  
Time Lapse ◽  
Post Injury ◽  
Injury Model ◽  
Time Lapse Imaging

AbstractTraumatic brain injury (TBI) is a major source of cognitive deficits affecting millions annually. The bulk of human injuries are mild, causing little or no macroscopic damage to neural tissue, yet can still lead to long-term neuropathology manifesting months or years later. Although the cellular stressors that ultimately lead to chronic pathology are poorly defined, one notable candidate is metabolic stress due to reduced cerebral blood flow (CBF), which is common to many forms of TBI. Here we used high-resolution in vivo intracranial imaging in a rodent injury model to characterize deficits in the cortical microcirculation during both acute and chronic phases after mild TBI. We found that CBF dropped precipitously during immediate post-injury periods, decreasing to less than half of baseline levels within minutes and remaining suppressed for 1.5-2 hours. Repeated time-lapse imaging of the cortical microvasculature revealed further striking flow deficits in the capillary network, where 18% of vessels were completely occluded for extended periods after injury, and an additional >50% showed substantial stoppages. Decreased CBF was paralleled by extensive vasoconstriction that is likely to contribute to loss of flow. Our data indicate a major role for vascular dysfunction in even mild forms of TBI, and suggest that acute post-injury periods may be key therapeutic windows for interventions that restore flow and mitigate metabolic stress.

scholarly journals Transient induction of cell cycle promoter Fam64a improves cardiac function through regulating Klf15-dependent cardiomyocyte differentiation in mice

2021 ◽  
Author(s):  
Ken Hashimoto ◽  
Aya Kodama ◽  
Momoko Ohira ◽  
Misaki Kimoto ◽  
Reiko Nakagawa ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcriptional Activation ◽  
Contractile Function ◽  
Cardiomyocyte Differentiation ◽  
Specific Expression ◽  
Calcium Dysregulation ◽  
Adult Mice ◽  
Endogenous Expression ◽  
Age Related

The introduction of fetal or neonatal signatures such as cell cycle promoting genes into damaged adult hearts has been vigorously pursued as a promising strategy for stimulating proliferation and regeneration of adult cardiomyocytes, which normally cannot divide. However, cell division of cardiomyocytes requires preceding dedifferentiation with sarcomere disassembly and calcium dysregulation, which, in principle, compromises contractile function. To overcome this intrinsic dilemma, we explored the feasibility of optimizing the induction protocol of the cell cycle promoter in mice. As a model of this approach, we used Fam64a, a fetal-specific cardiomyocyte cell cycle promoter that we have recently identified. We first analyzed transgenic mice maintaining long-term cardiomyocyte-specific expression of Fam64a after birth, when endogenous expression was abolished. Despite having an enhanced proliferation of postnatal cardiomyocytes, these mice showed age-related cardiac dysfunction characterized by sustained cardiomyocyte dedifferentiation, which was reminiscent of the dilemma. Mechanistically, Fam64a inhibited glucocorticoid receptor-mediated transcriptional activation of Klf15, a key regulator that drives cardiomyocyte differentiation, thereby directing cardiomyocytes toward immature undifferentiated states. In contrast, transient induction of Fam64a in cryoinjured wildtype adult mice hearts improved functional recovery with augmented cell cycle activation of cardiomyocytes. These data indicate that optimizing the intensity and duration of the stimulant to avoid excessive cardiomyocyte dedifferentiation could pave the way toward developing efficient strategy for successful heart regeneration.

scholarly journals Age-dependent changes in protein incorporation into collagen-rich tissues of mice by in vivo pulsed SILAC labelling

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Yoanna Ariosa-Morejon ◽  
Alberto Santos ◽  
Roman Fischer ◽  
Simon Davis ◽  
Philip Charles ◽  
...  
Keyword(s):  
Skeletal Maturity ◽  
Tissue Level ◽  
Skeletal Maturation ◽  
Healthy Life ◽  
Adult Mice ◽  
Age Related ◽  
Age Dependent ◽  
Protein Incorporation ◽  
New Protein

Collagen-rich tissues have poor reparative capacity that predisposes to common age-related disorders such as osteoporosis and osteoarthritis. We used in vivo pulsed SILAC labelling to quantify new protein incorporation into cartilage, bone, and skin of mice across the healthy life course. We report dynamic turnover of the matrisome, the proteins of the extracellular matrix, in bone and cartilage during skeletal maturation, which was markedly reduced after skeletal maturity. Comparing young adult with older adult mice, new protein incorporation was reduced in all tissues. STRING clustering revealed changes in epigenetic modulators across all tissues, a decline in chondroprotective growth factors such as FGF2 and TGFβ in cartilage, and clusters indicating mitochondrial dysregulation and reduced collagen synthesis in bone. Several pathways were implicated in age-related disease. Fewer changes were observed for skin. This methodology provides dynamic protein data at a tissue level, uncovering age-related molecular changes that may predispose to disease.

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