Association of monomeric C-Reactive Protein (m-CRP) with hypothalamic neurons after CRP hippo-campal administration
R S Al-Baradie1, A Abdel-Hadi, F Ahmad
1Department of Medical Laboratory Sciences, Department of Physical Therapy and Health Rehabilitation, College of Applied Medical Sciences, Majmaah University, Majmaah, Saudi Arabia. r.albaradie@mu.edu.sa.
Insights
Monomeric C-reactive protein (mCRP) spreads throughout the brain after stroke, causing inflammation and neurodegeneration. This protein exacerbates damage, potentially contributing to dementia development.
Area of Science:
- Neuroscience
- Pathology
- Immunology
Background:
- Ischemic stroke, caused by disrupted brain blood supply, is a leading cause of stroke.
- Ischemic injury is linked to vascular dementia and Alzheimer's disease (AD).
- Brain ischemia triggers inflammatory responses and oxidative stress, leading to neuronal damage.
Purpose of the Study:
- To investigate the role of monomeric C-reactive protein (mCRP) in post-stroke neurodegeneration and inflammation.
- To examine mCRP distribution and its effects in brain tissue following ischemic events.
Main Methods:
- Analysis of human brain samples and mouse brain tissue.
- Stereotactic injection of mCRP into the hippocampus of mice.
- Immunohistochemistry using mCRP-specific antibodies to track protein distribution over six months.
Main Results:
- A novel finding revealed that microvessels near the injection site in mice strongly stained for mCRP.
- This staining pattern indicates that small blood vessels can facilitate the spread of mCRP throughout the brain.
- mCRP was found to induce inflammation and degeneration in perivascular compartments.
Conclusions:
- Monomeric C-reactive protein (mCRP) present in the brain after hemorrhagic stroke contributes to widespread damage.
- mCRP promotes neurodegeneration and inflammation, particularly affecting perivascular compartments.
- These findings suggest mCRP plays a significant role in stroke-induced brain injury and potentially dementia progression.
Objective:
The ensuing ischemia due to the disruption of blood supply to the brain is one of the most common causes of stroke. Evidence suggests a clear association of the ischemic injury with vascular dementia and Alzheimer's disease (AD). In response to the brain ischemia, a cascade reaction starts leading to neuronal damage due to oxidative stress and other inflammatory mediators. A pilot study was done, which showed that following stroke, monomeric-C-reactive protein (mCRP) is expressed in large quantities around the infarcted zone and this CRP is able to induce neurodegeneration and inflammation potentially perpetuating dementia.
Materials And Methods:
We examined both patient brain samples and excised mouse brain tissue, previously injected with 1.75 mg/mL mCRP into the CA1 area of the hippocampus through the stereotactic surgical procedures and followed them over a period of over 6 months. The distribution of mCRP was examined through immunohistochemistry (mouse anti-human mCRP-specific antibodies 8C10).
Results:
We observed a novel finding: those micro vessels close to the injection location were strongly stained with mCRP only in the mice that had been injected with mCRP, indicating that this small blood vessel can spread it throughout the brain.
Conclusions:
mCRP found in the brain after a hemorrhagic stroke promotes damage over a large area via the induction of inflammation and degeneration of perivascular compartments.
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