Maria J. Sosa

Seattle Children's Hospital

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Andy Y. Shih

University of Washington

Stephanie Bonney

Seattle Children's Hospital

Cara D. Nielson

University of Washington

Franca Schmid

University of Bern

Nicolas Weitermann

Seattle Children's Hospital

Yongsoo Kim

Pennsylvania State University

Stefan Stamenković

Seattle Children's Hospital

Yuandong Li

Qingdao Institute of Bioenergy and Bioprocess Technology

Jack Waters

Allen Institute for Brain Science

Kevin Takasaki

Allen Institute

Cooperative Institutions

The University of Texas at Dallas

Texas Biomedical Research Institute

Universidad Anáhuac

Seattle Children's Hospital

University of Washington

Pennsylvania State University

Universidad Nacional Autónoma de México

Mexican Social Security Institute

Instituto de Investigaciones en Ciencias de la Salud

Allen Institute

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Capillary regression leads to sustained local hypoperfusion by inducing constriction of upstream transitional vessels

Proceedings of the National Academy of Sciences (2024)

Stephanie Bonney Cara D. Nielson Maria J. Sosa Orla Bonnar Andy Y. Shih

In the brain, a microvascular sensory web coordinates oxygen delivery to regions of neuronal activity. This involves a dense network of capillaries that send conductive signals upstream to feeding arterioles to promote vasodilation and blood flow. Although this process is critical to the metabolic supply of healthy brain tissue, it may also be a point of vulnerability in disease. Deterioration of capillary networks is a feature of many neurological disorders and injuries and how this web is engaged during vascular damage remains unknown. We performed in vivo two-photon microscopy on young adult mural cell reporter mice and induced focal capillary injuries using precise two-photon laser irradiation of single capillaries. We found that ~59% of the injuries resulted in regression of the capillary segment 7 to 14 d following injury, and the remaining repaired to reestablish blood flow within 7 d. Injuries that resulted in capillary regression induced sustained vasoconstriction in the upstream arteriole-capillary transition (ACT) zone at least 21 days postinjury in both awake and anesthetized mice. The degree of vasomotor dynamics was chronically attenuated in the ACT zone consequently reducing blood flow in the ACT zone and in secondary, uninjured downstream capillaries. These findings demonstrate how focal capillary injury and regression can impair the microvascular sensory web and contribute to cerebral hypoperfusion.

Constriction

Arteriole

10.1073/pnas.2321021121

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Vagus Nerve Stimulation Paired With Rehabilitative Training Enhances Motor Recovery After Bilateral Spinal Cord Injury to Cervical Forelimb Motor Pools

Neurorehabilitation and neural repair (2020)

Michael J. Darrow Miranda Torres Maria J. Sosa Tanya T. Danaphongse Zainab Haider

Closed-loop vagus nerve stimulation (VNS) paired with rehabilitative training has emerged as a strategy to enhance recovery after neurological injury. Previous studies demonstrate that brief bursts of closed-loop VNS paired with rehabilitative training substantially improve recovery of forelimb motor function in models of unilateral and bilateral contusive spinal cord injury (SCI) at spinal level C5/6. While these findings provide initial evidence of the utility of VNS for SCI, the injury model used in these studies spares the majority of alpha motor neurons originating in C7-T1 that innervate distal forelimb muscles. Because the clinical manifestation of SCI in many patients involves damage at these levels, it is important to define whether damage to the distal forelimb motor neuron pools limits VNS-dependent recovery. In this study, we assessed recovery of forelimb function in rats that received a bilateral incomplete contusive SCI at C7/8 and underwent extensive rehabilitative training with or without paired VNS. The study design, including planned sample size, assessments, and statistical comparisons, was preregistered prior to beginning data collection ( https://osf.io/ysvgf/ ). VNS paired with rehabilitative training significantly improved recovery of volitional forelimb strength compared to equivalent rehabilitative training without VNS. Additionally, VNS-dependent enhancement of recovery generalized to 2 similar, but untrained, forelimb tasks. These findings indicate that damage to alpha motor neurons does not prevent VNS-dependent enhancement of recovery and provides additional evidence to support the evaluation of closed-loop VNS paired with rehabilitation in patients with incomplete cervical SCI.

Forelimb

Vagus Nerve Stimulation

10.1177/1545968319895480

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Impaired drainage through capillary-venous networks contributes to age-related white matter loss

Research Square (Research Square) (2024)

Andy Y. Shih Stefan Stamenković Franca Schmid Nicolas Weitermann Kevin Takasaki

Abstract The gradual loss of cerebral white matter contributes to cognitive decline during aging. However, microvascular networks that support the metabolic demands of white matter remain poorly defined. We used in vivo deep multi-photon imaging to characterize microvascular networks that perfuse cortical layer 6 and corpus callosum, a highly studied region of white matter in the mouse brain. We show that these deep tissues are exclusively drained by sparse and wide-reaching venules, termed principal cortical venules, which mirror vascular architecture at the human cortical-U fiber interface. During aging, capillary networks draining into deep branches of principal cortical venules are selectively constricted, reduced in density, and diminished in pericyte numbers. This causes hypo-perfusion in deep tissues, and correlates with gliosis and demyelination, whereas superficial tissues become relatively hyper-perfused. Thus, age-related impairment of capillary-venular drainage is a key vascular deficit that contributes to the unique vulnerability of cerebral white matter during brain aging.

White (mutation)

10.21203/rs.3.rs-3949186/v1

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Citations (1)

Capillary regression leads to sustained local hypoperfusion by inducing constriction of upstream transitional vessels

bioRxiv (Cold Spring Harbor Laboratory) (2023)

Stephanie Bonney Cara D. Nielson Maria J. Sosa Andy Y. Shih

Constriction

10.1101/2023.10.28.564529

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Citations (1)

Prophylactic neuroprotection with A91 improves the outcome of spinal cord injured rats

Neuroscience Letters (2013)

Antonio Ibarra Maria J. Sosa Elisa García Adrian Flores Yolanda Cruz

10.1016/j.neulet.2013.08.048

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Citations (17)

Impaired drainage through capillary-venous networks contributes to age-related white matter loss

bioRxiv (Cold Spring Harbor Laboratory) (2024)

Stefan Stamenković Franca Schmid Nicolas Weitermann Kevin Takasaki Stephanie Bonney

The gradual loss of cerebral white matter contributes to cognitive decline during aging. However, microvascular networks that support the metabolic demands of white matter remain poorly defined. We used

Cognitive Decline

White (mutation)

White paper

10.1101/2024.02.11.579849

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Citations (2)