# The Role of Inflammation in Post-stroke Epileptogenesis

> **NIH NIH R01** · J. DAVID GLADSTONE INSTITUTES · 2021 · $189,000

## Abstract

PROJECT SUMMARY/ABSTRACT OF PARENT GRANT
Epilepsy is a common consequence of brain insults, such as brain injuries, status epilepticus, and cerebrocortical
stroke in the elderly and children. Despite ongoing research, there are no treatments that prevent epilepsy after
brain insults. Each year, 15 million people worldwide suffer a stroke. Stroke is followed by a latent period (month
to years) during which the brain goes through changes leading to the onset of chronic epilepsy. Understanding
the maladaptive process so the development of epilepsy (“epileptogenesis”) during the latent period can be
prevented or treated is the holy grail of epilepsy research.
Our data that formed the basis of this proposal suggest that persistent inflammation involving glial cells may be
a key component of epileptogenesis after stroke in rats. We previously found that cerebrocortical stroke leads to
neural reorganization in the thalamocortical system and that the thalamus becomes hyperexcitable within the
first week after stroke. Silencing the thalamic “hot spot” with optogenetic tools is sufficient to abort the epileptic
seizures in real-time. We previously showed these hot spots to be causally involved in epileptic seizures (after
the onset of chronic post-stroke epilepsy). They are associated with neural circuit plasticity co-localized with a
permanent and focal astrogliosis and microgliosis and a massive upregulation of C1q, an immune molecule of
the complement cascade, in the region that is causally involved in epileptic seizures. C1q is known for its role in
synaptic pruning and circuit plasticity during normal development in the visual system, but our findings suggest
that C1q may have a role in circuit plasticity after brain insults such as stroke. Our data indicate that anti-
inflammatory treatments that modify the gliosis also prevent the circuit hyperexcitability and deficits in synaptic
inhibition and that selectively inducing gliosis via viral approaches phenocopies the changes in synaptic inhibition
and induces circuit hyperexcitability.
We hypothesize that the glial-induced inflammation and C1q in the thalamus have key roles in the maladaptive
cellular and circuit plasticity that leads from stroke to epilepsy. The goal of the proposed research is to
determine the role of gliosis and mainly the complement pathway in epileptogenic circuit reorganization
in the thalamocortical system. We combine cellular physiology, systems neuroscience, and bioengineering to
determine whether blocking gliosis and/or C1q actions after stroke will prevent epileptogenesis and whether
blocking gliosis and/or C1q actions during the chronic epileptic phase (i.e., after epilepsy has developed) will be
sufficient to “go back in time” to modify the disease and cure epilepsy. This project may lead to novel biomarkers
in epilepsy (thalamic gliosis and C1q) and novel treatments to prevent epilepsy after brain lesions, such as
stroke.

## Key facts

- **NIH application ID:** 10318906
- **Project number:** 3R01NS096369-05S1
- **Recipient organization:** J. DAVID GLADSTONE INSTITUTES
- **Principal Investigator:** Jeanne T Paz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $189,000
- **Award type:** 3
- **Project period:** 2021-01-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10318906

## Citation

> US National Institutes of Health, RePORTER application 10318906, The Role of Inflammation in Post-stroke Epileptogenesis (3R01NS096369-05S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10318906. Licensed CC0.

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