# B Cells Directly Alter Adaptive Plasticity to Support Functional Recovery After Stroke

> **NIH NIH RF1** · UNIVERSITY OF KENTUCKY · 2021 · $1,176,279

## Abstract

The central hypothesis of this R01 renewal focuses on a subset of B cells that provide neurotrophic support to counter cognitive impairment and improve motor function after ischemic stroke, a key risk factor for the development of vascular contributions to cognitive impairment and dementia (VCID). These neurotrophic B cells secrete brain-derived neurotrophic factor (BDNF) and may be critical to countering the development of VCID. Unfortunately, the patient population most at risk for stroke and VCID aged individuals have impaired B cell development and secretion of growth factors that could limit protection from post-stroke depression and dementia. Sex is also a factor, as elderly women with post-stroke dementia have the lowest levels of circulating BDNF, though no prior studies have directly linked a loss of neurotrophic immune cell populations and the development of VCID. Based on our pilot data, we will test: if a subset of post-stroke B cells (i.e. B cellsBDNF+) upregulate BDNF after encountering glutamate; if B cellsBDNF+ limit the development of VCID and support motor recovery; and if B cell-derived BDNF is impaired in aged females. We will use 4 mos. (“young”) and 16 mos. (“aged”) female and male mice to test if B cellsBDNF+ support neuronal function, plasticity, motor, and multi-domain cognitive recovery post-stroke. Aim 1 will test if after stroke, (1A) glutamate binds to B cells to increase BDNF production and drive recovery-linked intracellular Ca2+ signaling that is sex- and age-dependent. We will (1B) use B cellsNtrk2tm1Ddg/J in vitro to test if the BDNF receptor TrkB is required for BDNF production and in vitro neuroprotection. Aim 2 will test if B cellsBDNF+ support remote plasticity, as well as cognitive and motor recovery in a primary motor cortex (M1) photothrombosis stroke model. Inducible depletion of (2A) all B cells or (2B) specific B cell-derived BDNF in young and aged female hCD20TamCre/ BDNFfl/fl mice and littermate controls will occur either acute (day 0) or delayed (beginning day 7 post-stroke). Primary outcomes will include 1) preservation of Pavlovian stimulus-reinforcer learning on an automated touchscreen task, 2) improved forelimb precision reaching, and 3) peri-infarct and contralesional M1 plasticity. Aim 3 will test if B cell-derived BDNF augments long-term cognitive and motor recovery. Aged C57BL/6J female mice will receive tMCAo or sham surgery and adoptive transfer of B cells that (3A) overexpress BDNF or (3B) lack BDNF, the latter derived from hCD20TamCre/BDNFfl/fl donor mice, beginning day 7 post-stroke. Primary outcomes will include 1) ameliorated hippocampal-specific cognitive deficits tested via touchscreen pattern separation, 2) improved precision skilled reaching, and 3) regional ipsi- and contralesional diapedesis of B cells, as determined via whole brain serial two-photon tomography, that correlates to within-animal magnitude of brain circuit-specific cognitive function and motor recovery. These stud...

## Key facts

- **NIH application ID:** 10304343
- **Project number:** 2RF1NS088555-07A1
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Ann Marie Stowe
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,176,279
- **Award type:** 2
- **Project period:** 2015-02-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10304343

## Citation

> US National Institutes of Health, RePORTER application 10304343, B Cells Directly Alter Adaptive Plasticity to Support Functional Recovery After Stroke (2RF1NS088555-07A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10304343. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*