# Mechanism of memory decline after intra-ventricular hemorrhage

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $196,872

## Abstract

Abstract
Intellectual deficits are common following intraventricular hemorrhage (IVH) and subarachnoid
hemorrhage (SAH). Cognitive deficits often include anterograde and retrograde amnesia and deficits
in spatial memory function which points towards hippocampal injury. In our preliminary data, we have
developed a model of intraventricular blood (IVB) and intraventricular thrombin (IVT) which produces a
significantly worse performance in the Morris water maze paradigm 5 weeks after the injection
compared to sham surgery. We did not see obvious neuronal loss in the dentate gyrus or hippocampus
at this time point. However, we saw a significant impairment in dentate neurogenesis as evidenced by
vastly reduced numbers of dividing progenitor cells and failure of dentate progenitor cells to differentiate
into new neurons. Spatial memory deficits after IVT could be inhibited by the src inhibitor PP2. This
finding has led us to the hypothesis that the decrease in dentate progenitor cells is due to thrombin
activation of the src pathway through protease-activated receptor 1 (PAR1). The grant will test this
hypothesis and identify further members of the signaling cascade with RNA sequencing. We are
especially interested in linking known regulators of the dentate progenitor cell maintenance and
differentiation pathways such as WNT-3A or sonic hedgehog to our preliminary finding of src pathway
activation. The grant is aimed to identify a pipeline of candidate genes which are implicated in the
hemorrhage-induced decline of the pool of dentate progenitor cells. Identification of candidate genes
will serve as the basis for an R01 application towards the end of the K08 period. My mentor Frank
Sharp is ideal for this project due to his extensive experience with dentate neurogenesis in the setting of
hemorrhage or ischemia as well as his experience with whole-genome transcriptome studies. This grant
proposal is aimed to understand the genomic mechanism of memory dysfunction that we see after
intraventricular hemorrhage to develop therapies to treat this important clinical problem.

## Key facts

- **NIH application ID:** 9886294
- **Project number:** 5K08NS105914-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** BEN WALDAU
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $196,872
- **Award type:** 5
- **Project period:** 2018-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9886294

## Citation

> US National Institutes of Health, RePORTER application 9886294, Mechanism of memory decline after intra-ventricular hemorrhage (5K08NS105914-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9886294. Licensed CC0.

---

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