Stroke affects millions each year. Poststroke brain edema predicts the severity of eventual stroke damage, yet our concept of how edema develops is incomplete and treatment options remain limited. In ...early stages, fluid accumulation occurs owing to a net gain of ions, widely thought to enter from the vascular compartment. Here, we used magnetic resonance imaging, radiolabeled tracers, and multiphoton imaging in rodents to show instead that cerebrospinal fluid surrounding the brain enters the tissue within minutes of an ischemic insult along perivascular flow channels. This process was initiated by ischemic spreading depolarizations along with subsequent vasoconstriction, which in turn enlarged the perivascular spaces and doubled glymphatic inflow speeds. Thus, our understanding of poststroke edema needs to be revised, and these findings could provide a conceptual basis for development of alternative treatment strategies.
Electrical and chemical synapses shape the dynamics of neural networks and their functional roles in information processing has been a longstanding question in neurobiology. In this paper, we ...investigate the role of synapses on the optimization of the phenomenon of self-induced stochastic resonance in a delayed multiplex neural network by using analytical and numerical methods. We consider a two-layer multiplex network, in which at the intra-layer level neurons are coupled either by electrical synapses or by inhibitory chemical synapses. For each isolated layer, computations indicate that weaker electrical and chemical synaptic couplings are better optimizers of self-induced stochastic resonance. In addition, regardless of the synaptic strengths, shorter electrical synaptic delays are found to be better optimizers of the phenomenon than shorter chemical synaptic delays, while longer chemical synaptic delays are better optimizers than longer electrical synaptic delays --- in both cases, the poorer optimizers are in fact worst. It is found that electrical, inhibitory, or excitatory chemical multiplexing of the two layers having only electrical synapses at the intra-layer levels can each optimize the phenomenon. And only excitatory chemical multiplexing of the two layers having only inhibitory chemical synapses at the intra-layer levels can optimize the phenomenon. These results may guide experiments aimed at establishing or confirming the mechanism of self-induced stochastic resonance in networks of artificial neural circuits, as well as in real biological neural networks.
We review theoretical and numerical models of the glymphatic system, which circulates cerebrospinal fluid and interstitial fluid around the brain, facilitating solute transport. Models enable ...hypothesis development and predictions of transport, with clinical applications including drug delivery, stroke, cardiac arrest, and neurodegenerative disorders like Alzheimer’s disease. We sort existing models into broad categories by anatomical function: Perivascular flow, transport in brain parenchyma, interfaces to perivascular spaces, efflux routes, and links to neuronal activity. Needs and opportunities for future work are highlighted wherever possible; new models, expanded models, and novel experiments to inform models could all have tremendous value for advancing the field.
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Neuroscience; Neuroanatomy; Systems biology
This paper presents a brief review of how industrial mathematics, inspired by the Oxford Study Group activity, organized itself in Europe, gave rise to the European Consortium for Mathematics in ...Industry, the series of European Study Groups with Industry, and to new modes of productive contacts between industry and applied mathematicians in academia.
Modeling of brain efflux: Constraints of brain surfaces Bork, Peter A R; Hauglund, Natalie L; Mori, Yuki ...
Proceedings of the National Academy of Sciences - PNAS,
2024-Apr-16, 2024-04-16, 20240416, Letnik:
121, Številka:
16
Journal Article
Recenzirano
Fluid efflux from the brain plays an important role in solute waste clearance. Current experimental approaches provide little spatial information, and data collection is limited due to short duration ...or low frequency of sampling. One approach shows tracer efflux to be independent of molecular size, indicating bulk flow, yet also decelerating like simple membrane diffusion. In an apparent contradiction to this report, other studies point to tracer efflux acceleration. We here develop a one-dimensional advection-diffusion model to gain insight into brain efflux principles. The model is characterized by nine physiological constants and three efflux parameters for which we quantify prior uncertainty. Using Bayes' rule and the two efflux studies, we validate the model and calculate data-informed parameter distributions. The apparent contradictions in the efflux studies are resolved by brain surface boundaries being bottlenecks for efflux. To critically test the model, a custom MRI efflux assay measuring solute dispersion in tissue and release to cerebrospinal fluid was employed. The model passed the test with tissue bulk flow velocities in the range 60 to 190 Formula: see textm/h. Dimensional analysis identified three principal determinants of efflux, highlighting brain surfaces as a restricting factor for metabolite solute clearance.
Supported by chl a satellite data in the North Atlantic (and phytoplankton division rates computed from that data), the disturbance−recovery hypothesis for the initiation of phytoplankton blooms ...posits that the change in chl a concentration is proportional to the relative change in the phytoplankton division rate. We used this hypothesis, introduced by Behrenfeld, as a principal model assumption and constructed a non-autonomous ordinary differential equation model for seasonally varying chl a concentrations. Our quantitative comparison between model simulations and in situ measurements of chl a and primary production collected from a Swedish fjord was 2-fold: first, using approximate Bayesian computations, we found distributions of values for the 3 model parameters that best described the chl a data. Then, we validated our model by comparing the simulated (not fitted) division rate to the division rate determined from the data. Our minimalistic model was able to capture (1) the yearly trend in the chl a concentration, (2) the pattern of growth and decline in the phytoplankton division rate, and (3) the decreasing trend in the relative change of the division rate exhibited in the data for several individual years. Moreover, the modeling efficiency was positive (between 0.3 and 0.9 with an average of 0.63) for all 11 yr included in this study. We conclude that the change in chl a concentration being proportional to the relative change in the division rate is a possible explanation for the bloom dynamics in the Gullmar fjord. In addition, our work provides a simple and empirically based differential equation for representing yearly dynamics of primary production, e.g. for generating ecological hypotheses using models of other trophic levels.
Cerebral oedema develops after anoxic brain injury. In two models of asphyxial and asystolic cardiac arrest without resuscitation, we found that oedema develops shortly after anoxia secondary to ...terminal depolarizations and the abnormal entry of CSF. Oedema severity correlated with the availability of CSF with the age-dependent increase in CSF volume worsening the severity of oedema. Oedema was identified primarily in brain regions bordering CSF compartments in mice and humans. The degree of ex vivo tissue swelling was predicted by an osmotic model suggesting that anoxic brain tissue possesses a high intrinsic osmotic potential. This osmotic process was temperature-dependent, proposing an additional mechanism for the beneficial effect of therapeutic hypothermia. These observations show that CSF is a primary source of oedema fluid in anoxic brain. This novel insight offers a mechanistic basis for the future development of alternative strategies to prevent cerebral oedema formation after cardiac arrest.
Integrated Inflammatory Stress (ITIS) Model Bangsgaard, Elisabeth O.; Hjorth, Poul G.; Olufsen, Mette S. ...
Bulletin of mathematical biology,
07/2017, Letnik:
79, Številka:
7
Journal Article
Recenzirano
Odprti dostop
During the last decade, there has been an increasing interest in the coupling between the acute inflammatory response and the Hypothalamic–Pituitary–Adrenal (HPA) axis. The inflammatory response is ...activated acutely by pathogen- or damage-related molecular patterns, whereas the HPA axis maintains a long-term level of the stress hormone cortisol which is also anti-inflammatory. A new integrated model of the interaction between these two subsystems of the inflammatory system is proposed and coined the integrated inflammatory stress (ITIS) model. The coupling mechanisms describing the interactions between the subsystems in the ITIS model are formulated based on biological reasoning and its ability to describe clinical data. The ITIS model is calibrated and validated by simulating various scenarios related to endotoxin (LPS) exposure. The model is capable of reproducing human data of tumor necrosis factor alpha, adrenocorticotropic hormone (ACTH) and cortisol and suggests that repeated LPS injections lead to a deficient response. The ITIS model predicts that the most extensive response to an LPS injection in ACTH and cortisol concentrations is observed in the early hours of the day. A constant activation results in elevated levels of the variables in the model while a prolonged change of the oscillations in ACTH and cortisol concentrations is the most pronounced result of different LPS doses predicted by the model.
Using an equation-free analysis approach we identify a Hopf bifurcation point and perform a two-parameter continuation of the Hopf point for the macroscopic dynamical behavior of an interacting ...particle model. Due to the nature of systems with a moderate number of particles and noise, the quality of the available numerical information requires the use of very robust numerical algorithms for each of the building blocks of the equation-free methodology. As an example, we consider a particle model of a crowd of pedestrians where particles interact through pairwise "social forces." The pedestrians move along a corridor where they are constrained by the walls of the corridor, and two crowds are aiming, from opposite directions, to pass through a narrowing doorway perpendicular to the corridor. We focus our investigation on the collective behavior of the model. As the width of the doorway is increased, we observe an onset of oscillations of the net pedestrian flux through the doorway, described by a Hopf bifurcation. An equation-free continuation of the Hopf point in the two parameters, door width and ratio of the pedestrian velocities of the two crowds, is performed. PUBLICATION ABSTRACT
This paper presents a brief review of how industrial mathematics, inspired by the Oxford Study Group activity, organized itself in Europe, gave rise to the European Consortium for Mathematics in ...Industry, the series of European Study Groups with Industry, and to new modes of productive contacts between industry and applied mathematicians in academia.
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