# CALCIFICATION AND LACUNE FORMATION IN AGED RAT BRAIN

> **NIH NIH R01** · CREIGHTON UNIVERSITY · 1993 · $184,158

## Abstract

The goal is to study a new hypothesis of the mechanism which produces
"lacunes" and "lipohyalinosis"; probable misinterpretation of autopsy
findings (obtained months or years after the clinical stroke) has led to
the concept that lacunes result from "intrinsic small vessel disease" due
to hypertension or diabetes.  This misconception continues to have a
detrimental effect on patients with this type of stroke, as diagnostic
evaluation is often not done, and preventative therapy is often limited
to treatment of hypertension and diabetes.  Multiple small embolic
cerebral infarcts will be studied in aged rats, which are most
appropriate to the study of diseases associated with aging.  The right
carotid artery of aged and young Fisher rats will be irradiated with a
laser (632 nm, 200 mW/cm2, 15 minutes) following the intravenous
injection of the photosensitizing dye, Photofrin II, 12.5 mg/kg.  A non-
occlusive thrombus is produced, which embolizes spontaneously, producing
multiple small cerebral infarcts acutely, and lacunes chronically.  A
small portion of embolic infarcts become hemorrhagic; these hemorrhagic
areas will be studied by scanning electron microscopy and energy
dispersive x-ray microanalysis, to determine whether they calcify.
Calcifications occur in chronic (2 weeks or more) infarcts in this rat
model.  Astrocytic processes will be stained with GFAP to determine
whether they enter the calcified area, or whether this physical barrier
induces the formation of a glial limitans which may form the wall of a
cavity (lacune).  The frequency of calcium in association with lacunes,
and the percent of calcified lesions which cavitate by 12 weeks, will be
determined.  Recanilizing platelet emboli will be studied, as lipid laden
macrophages accumulate in emboli by 5 days.  The "thickened" vessel wall
could actually be a recanalized platelet embolus, with a lipid component
which originated in the macrophages.  Immunoperoxidase stains for
platelets and endothelium may demonstrate a "vessel wall" composed of
platelets, and 2 layers of endothelium, one surrounding the platelets and
one forming a lumen within the mass of platelets (original and neo-
endothelium).  Thus, platelet emboli could produce all the features
associated with lacunes, including cavitation and "lipohyalinosis";
lipohyalinosis could be the result of embolization rather than the cause
of focal cerebral ischemia.  This data would have an important influence
on patient care, as diagnostic evaluation for an embolic source would be
a high priority in patients with "lacunar" strokes, and additional
potential therapeutic strategies could be considered.  The frequency and
extent of tissue retraction will be studied, as retraction of cerebral
infarcts could alter imaging characteristics, leading to the potential
misdiagnosis of Alzheimer's disease in some patients with multi-infarct
dementia.  Old and young animals will be compared, to study the effect
of aging on these processes.

## Key facts

- **NIH application ID:** 3123616
- **Project number:** 1R01AG011759-01
- **Recipient organization:** CREIGHTON UNIVERSITY
- **SAM.gov UEI:** NH64NT271S93
- **Principal Investigator:** NANCY N FUTRELL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $184,158
- **Award type:** 1
- **Project period:** 1993-02-01 → 1997-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3123616

## Citation

> US National Institutes of Health, RePORTER application 3123616, CALCIFICATION AND LACUNE FORMATION IN AGED RAT BRAIN (1R01AG011759-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3123616. Licensed CC0.

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