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Updated: Jan 22, 2026

Assay for Blood-brain Barrier Integrity in Drosophila melanogaster
Published on: September 18, 2019
N-acetylcysteine Amide Ameliorates Blast-Induced Changes in Blood-Brain Barrier Integrity in Rats
Usmah Kawoos1,2, Rania Abutarboush1,2, Sydney Zarriello3
1The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, United States.
Blast overpressure (BOP) exposure damages the blood-brain barrier (BBB). Post-blast treatment with N-acetylcysteine amide (NACA) significantly protected against this blast-induced BBB breakdown in rats.
Area of Science:
- Neuroscience
- Trauma Research
- Pharmacology
Background:
- Traumatic brain injury from blast overpressure (BOP) is linked to neuropathology, including blood-brain barrier (BBB) dysfunction.
- Understanding BBB integrity following BOP exposure is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the effects of repeated BOP exposure on BBB integrity.
- To evaluate the protective potential of N-acetylcysteine amide (NACA) against blast-induced BBB damage.
Main Methods:
- Rats were exposed to three BOPs (110 kPa) with 0.5-hour intervals.
- BBB integrity was assessed in vivo using intravital microscopy and TRITC-Dextran leakage into the brain parenchyma.
- NACA treatment was administered 2 hours after the initial BOP exposure.
Main Results:
- BOP exposure significantly increased TRITC-Dextran leakage, indicating BBB compromise.
- NACA treatment markedly reduced TRITC-Dextran leakage in BOP-exposed rats.
- Sham-treated animals receiving NACA showed minimal leakage, suggesting a protective effect.
Conclusions:
- Repeated BOP exposure compromises BBB integrity.
- N-acetylcysteine amide (NACA) demonstrates significant protective effects against blast-induced BBB breakdown.
- NACA is a potential therapeutic agent for mitigating blast-related brain injury.
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The Blood-brain Barrier
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The DCC-promoted synthesis of amides begins with the protonation of DCC by carboxylic acid. The protonation makes it a better acceptor. Next, the addition of carboxylate to the protonated carbodiimide gives a reactive acylating agent.
Subsequently, the amine acts as a nucleophile that attacks the acylating agent to form a tetrahedral intermediate. In the...
Amides to Carboxylic Acids: Hydrolysis
Acid-catalyzed hydrolysis:
Hydrolysis of amides under acidic conditions yields carboxylic acids. Since the reaction occurs slowly, hydrolysis requires the conditions of heat.
The mechanism begins with the protonation of the carbonyl oxygen by the acid catalyst. The protonation makes the amide carbonyl carbon more...
Amines to Amides: Acylation of Amines
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary...
Acid Halides to Amides: Aminolysis
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
Amides to Amines: LiAlH4 Reduction
Amide reduction requires two equivalents of the reducing agent, acting as a source of hydride ions. As shown in the figure, the reaction is initiated with a nucleophilic attack by the hydride ion at the carbonyl carbon to form a tetrahedral intermediate.

