The severity of microstrokes depends on local vascular topology and baseline perfusion
Abstract
Cortical microinfarcts are linked to pathologies like cerebral amyloid angiopathy and dementia. Despite their relevance for disease progression, microinfarcts often remain undetected and the smallest scale of blood flow disturbance has not yet been identified. We employed blood flow simulations in realistic microvascular networks from the mouse cortex to quantify the impact of single capillary occlusions. Our simulations reveal that the severity of a microstroke is strongly affected by the local vascular topology and the baseline flow rate in the occluded capillary. The largest changes in perfusion are observed in capillaries with two in- and two outflows. This specific topological configuration only occurs with a frequency of 8%. The majority of capillaries has one in- and one outflow and is likely designed to efficiently supply oxygen and nutrients. Taken together, microstrokes bear potential to induce a cascade of local disturbances in the surrounding tissue, which might accumulate and impair energy supply locally.
Data availability
We provide all time-averaged simulation results as well as relevant analysis scripts.
Article and author information
Author details
Funding
University of Zurich - Forschungskredit (FK-19-045)
- Franca Schmid
European Union's Horizon 2020 Framework Program for Research and Innovation (Specific Grant Agreement No. 720270 (Human Brain Project SGA1))
- Franca Schmid
European Union's Horizon 2020 Framework Program for Research and Innovation (Specific Grant Agreement No. 785907 (Human Brain Project SGA2))
- Franca Schmid
Swiss National Science Foundation (310030_182703)
- Bruno Weber
Swiss National Science Foundation (SNF CR23I2_166707)
- Bruno Weber
Swiss National Science Foundation (SNF CR23I2_166707)
- Patrick Jenny
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Schmid et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 1,646
- views
-
- 230
- downloads
-
- 23
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Neuroscience
Active vision, the sensory-motor process through which animals dynamically adjust visual input to sample and prioritise relevant information via photoreceptors, eyes, head, and body movements, is well-documented across species. In small-brained animals like insects, where parallel processing may be limited, active vision for sequential acquisition of visual features might be even more important. We investigated how bumblebees use active vision to distinguish between two visual patterns: a multiplication sign and its 45°-rotated variant, a plus sign. By allowing bees to freely inspect patterns, we analysed their flight paths, inspection times, velocities and regions of focus through high-speed videography. We observed that bees tended to inspect only a small region of each pattern, with a preference for lower and left-side sections, before accurately accepting target or rejecting distractor patterns. The specific pattern areas scanned differed between the plus and multiplication signs, yet flight behaviour remained consistent and specific to each pattern, regardless of whether the pattern was rewarding or punishing. Transfer tests showed that bees could generalise their pattern recognition to partial cues, maintaining scanning strategies and selective attention to learned regions. These findings highlight active vision as a crucial aspect of bumblebees' visual processing, where selective scanning behaviours during flight enhance discrimination accuracy and enable efficient environmental analysis and visual encoding.
-
- Neuroscience
Mental and behavioral disorders are associated with extended period of hot weather as found in heatwaves, but the underlying neural circuit mechanism remains poorly known. The posterior paraventricular thalamus (pPVT) is a hub for emotional processing and receives inputs from the hypothalamic preoptic area (POA), the well-recognized thermoregulation center. The present study was designed to explore whether chronic heat exposure leads to aberrant activities in POA recipient pPVT neurons and subsequent changes in emotional states. By devising an air heating paradigm mimicking the condition of heatwaves and utilizing emotion-related behavioral tests, viral tract tracing, in vivo calcium recordings, optogenetic manipulations, and electrophysiological recordings, we found that chronic heat exposure for 3 weeks led to negative emotional valence and hyperarousal states in mice. The pPVT neurons receive monosynaptic excitatory and inhibitory innervations from the POA. These neurons exhibited a persistent increase in neural activity following chronic heat exposure, which was essential for chronic heat-induced emotional changes. Notably, these neurons were also prone to display stronger neuronal activities associated with anxiety responses to stressful situations. Furthermore, we observed saturated neuroplasticity in the POA-pPVT excitatory pathway after chronic heat exposure that occluded further potentiation. Taken together, long-term aberration in the POA to pPVT pathway offers a neurobiological mechanism of emotional and behavioral changes seen in extended periods of hot weather like heatwaves.