Revealing in vivo cellular mechanisms of cerebral microbleeds on neurons and microglia across cortical layers

Qianru Yang; Alberto L Vazquez; X Tracy Cui

doi:10.1016/j.isci.2024.109371

Revealing in vivo cellular mechanisms of cerebral microbleeds on neurons and microglia across cortical layers

iScience. 2024 Mar 2;27(4):109371. doi: 10.1016/j.isci.2024.109371. eCollection 2024 Apr 19.

Authors

Qianru Yang^{1

2

3}, Alberto L Vazquez^{3

4

5}, X Tracy Cui^{2

3

5}

Affiliations

¹ Department of Neurosurgery, Stanford University, Palo Alto, CA, USA.
² Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.
³ Center for Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, Pittsburgh, PA, USA.
⁴ Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA.
⁵ McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Abstract

Cerebral microbleeds (CMBs) are associated with higher risk for various neurological diseases including stroke, dementia, and Alzheimer's disease. However, the understanding of cellular pathology of CMBs, particularly in deep brain regions, remains limited. Utilizing two-photon microscopy and microprism implantation, we longitudinally imaged the impact of CMBs on neuronal and microglial activities across cortical depths in awake mice. A temporary decline in spontaneous neuronal activity occurred throughout cortical layers, followed by recovery within a week. However, significant changes of neuron-neuron activity correlations persisted for weeks. Moreover, microglial contact with neuron soma significantly increased post-microbleeds, indicating an important modulatory role of microglia. Notably, microglial contact, negatively correlated with neuronal firing rate in normal conditions, became uncorrelated after microbleeds, suggesting a decreased neuron-microglia inhibition. These findings reveal chronic alterations in cortical neuronal networks and microglial-neuronal interactions across cortical depths, shedding light on the pathology of CMBs.

Keywords: Cell biology; Cellular neuroscience; Molecular neuroscience; Neuroscience.