# Lymphatic support of neurogenesis and regeneration

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $21,503

## Abstract

PROJECT SUMMARY
The lymphatic vasculature plays a critical role in fluid homeostasis, removing cellular waste and immune
responses. Recent research has highlighted its integral contribution during the regenerative response after
cardiac injury. The central nervous system was until recently, believed to be immune privileged and lacking a
lymphatic system. Recent studies have revealed the lymphatic system extends into the mammalian and
zebrafish brain, however the role it plays in neurogenesis and the response to injury is unknown. The need to
better understand how to alleviate the detrimental responses to Traumatic brain injury (TBI) and stroke and
promote regeneration is imperative in order to improve outcomes. This proposal aims to uncover the role of the
meningeal lymphatic system in adult neurogenesis and regeneration and the mechanisms through which it
contributes to generating new neurons during homeostasis and injury response.
 Previously, we have characterized the development of the zebrafish cardiac lymphatic system and
identified the signaling pathways that regulate its specification and formation. We then demonstrated that the
cardiac lymphatic vasculature expands post injury in the adult zebrafish heart. This work demonstrated that
lymphatic vessels respond to injury and aid the regenerative response by trafficking immune cells. By blocking
lymphangiogenesis we demonstrated that the lymphatic vasculature was required to promote regeneration and
prevent scarring of heart tissue. The discovery of the meningeal lymphatics led us to hypothesize that
meningeal lymphatics support adult neurogenesis and regenerative repair after injury by providing
neurotropic factors, controlling cerebral spinal fluid (CSF) composition and the immune response.
 To test this hypothesis, we will pursue two aims in the zebrafish as a model of adult neurogenesis and
brain regeneration. Aim 1 will characterize the lymphatic response to injury using time lapse imaging and
determine how disruption of the lymphatic system impacts adult neurogenesis. Using mass spectrometry, we
will analyze the composition of the CSF to identify lymphangiocrine factors that support neurogenesis. In Aim 2
we will manipulate the development of the meningeal lymphatic vasculature and use transcriptomic analyses to
determine the impact on immune cell populations and response.
 Pursuit of these hypotheses will open new avenues for investigation of lymphatic support of neurogenesis
in mammalian systems in health and after injury. In order to further our comprehension of adult neurogenesis,
the regenerative response of the nervous system and potential therapies forward it is critical to understand the
how the lymphatic system modulates the immune and environmental aspects of neurogenesis and regeneration.

## Key facts

- **NIH application ID:** 10991768
- **Project number:** 3R01NS126209-02S1
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Michael Harrison
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $21,503
- **Award type:** 3
- **Project period:** 2022-12-01 → 2027-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10991768

## Citation

> US National Institutes of Health, RePORTER application 10991768, Lymphatic support of neurogenesis and regeneration (3R01NS126209-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10991768. Licensed CC0.

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