# Inhibition of Fibrinogen Reduces Brain Injury and Hydrocephalus in Premature Neonates with Intraventricular Hemorrhage

> **NIH NS R21** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2026 · $462,000

## Abstract

ABSTRACT
The occurrence of intraventricular hemorrhage (IVH) leads to posthemorrhagic white matter injury (WMI) and
hydrocephalus. No optimal therapeutic strategy exists to minimize these complications of IVH. The occurrence
of IVH results in the formation of fibrin clots in the ventricle and extravasation of blood in the periventricular brain
parenchyma. Fibrin accumulation in the brain triggers inflammation, promotes scarring, and inhibits the
maturation of oligodendrocyte precursor cells, leading to WMI. Furthermore, fibrin clots block the intraventricular
CSF pathways, meningeal lymphatics, villi, and perineural routes, contributing to both obstructive and
communicating hydrocephalus. Therefore, the degradation or inhibition of fibrinogen is expected to alleviate both
hydrocephalus and WMI in IVH. We will employ two strategies to minimize post-hemorrhagic hydrocephalus and
WMI. First, we will administer a tissue-plasminogen activator (t-PA) to lyse the clot in the ventricles and in the
routes of CSF exit to reduce hydrocephalus. Moreover, t-PA is a neuroprotectant and has been shown to protect
against WMI in models of traumatic brain injury and hypoxia-ischemia. To enhance efficacy and minimize
adverse effects, we will employ thrombus-targeted delivery of t-PA, encapsulating it in lipid nanovesicles for
selective and gradual release at the site of the clot. Second, we will inhibit the binding of fibrinogen γ chain (γ377-
395) to CD11B-CD18 integrin receptor using either fibrin-derived γ377-395 peptide or 5B8 monoclonal antibody
to prevent microglial activation, reduce inflammation, and thereby minimize WMI and hydrocephalus. Indeed,
fibrin-targeted immunotherapy reduces inflammation, oxidative stress, and neurological dysfunction in animal
models of several neurological diseases. Despite the powerful premises, the role of fibrinogen in IVH-induced
brain injury remains obscure. We hypothesize that a) extravasation of fibrinogen in the brain parenchyma and
formati

## Key facts

- **NIH application ID:** 11304629
- **Project number:** 1R21NS140784-01A1
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** PRAVEEN  BALLABH
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NS
- **Fiscal year:** 2026
- **Award amount:** $462,000
- **Award type:** 1
- **Project period:** 2026-04-01T00:00:00 → 2028-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11304629

## Citation

> US National Institutes of Health, RePORTER application 11304629, Inhibition of Fibrinogen Reduces Brain Injury and Hydrocephalus in Premature Neonates with Intraventricular Hemorrhage (1R21NS140784-01A1). Retrieved via AI Analytics 2026-05-20 from https://api.ai-analytics.org/grant/nih/11304629. Licensed CC0.

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