Induction of Cerebral Microhemorrhages in a Rat Model Using Lipopolysaccharide

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Begin by intraperitoneally injecting lipopolysaccharide (LPS), a bacterial component, into an adult rat. 

LPS enters the bloodstream and binds to specific receptors on immune cells, triggering the release of inflammatory cytokines.

These cytokines reach the brain and activate the endothelial cells lining the cerebral blood vessels, increasing the expression of adhesion molecules and disrupting tight junction proteins, which increases the permeability of the blood-brain barrier (BBB).

Neutrophils adhere to the adhesion molecules and migrate across the BBB into the brain tissue.

Subsequently, the neutrophils release proteolytic enzymes and reactive oxygen species, which induce neuronal death and cause damage to brain tissue.

The cerebral blood vessels rupture, allowing blood cells to leak into the brain tissue.

Microglia then engulf these blood cells and convert hemoglobin to hemosiderin, a brown iron-containing pigment.

Hemosiderin deposits in the perivascular region mark the formation of cerebral microhemorrhages.

Administer LPS at a dose of 1 milligram per kilogram of body weight to 10-week-old male Sprague-Dawley rats by intraperitoneal injection. Then, return each rat to the home cage. Repeat the LPS injection after six hours and 16 hours.

Please note that injecting SD rats with LPS at a dose of 1 milligram per kilogram may result in a 5% mortality. The mortality could further increase in younger or older rats or pregnant female rats.

Return the rats to their cages after LPS injection, and provide ad libitum access to food and drink.

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Last updated: 27 June 2026