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Microvascular Embolism Mouse Model for In Vivo Two-photon Microscopy Using Fluorescent Polystyrene Microspheres
Published on: November 21, 2025
Experimental microembolism induces localized neuritic pathology in guinea pig cerebrum
Jian-Ming Li1,2, Yan Cai1, Fei Liu3
1Department of Anatomy and Neurobiology, Central South University School of Basic Medical Science, Changsha, Hunan, China.
Abstract:
Microbleeds are a common finding in aged human brains. In Alzheimer's disease (AD), neuritic plaques composed of β-amyloid (Aβ) deposits and dystrophic neurites occur frequently around cerebral vasculature, raising a compelling question as to whether, and if so, how, microvascular abnormality and amyloid/neuritic pathology might be causally related. Here we used a guinea pig model of cerebral microembolism to explore a potential inductive effect of vascular injury on neuritic and amyloid pathogenesis. Brains were examined 7-30 days after experimental microvascular embolization occupying ~0.5% of total cortical area. Compared to sham-operated controls, glial fibrillary acidic protein immunoreactivity was increased in the embolized cerebrum, evidently around intracortical vasculature. Swollen/sprouting neurites exhibiting increased reactivity of nicotinamide adenine dinucleotide phosphate diaphorase, parvalbumin, vesicular glutamate transporter 1 and choline acetyltransferase appeared locally in the embolized brains in proximity to intracortical vasculature. The embolization-induced swollen/sprouting neurites were also robustly immunoreactive for β-amyloid precursor protein and β-secretase-1, the substrate and initiating enzyme for Aβ genesis. These experimental data suggest that microvascular injury can induce multisystem neuritic pathology associated with an enhanced amyloidogenic potential in wild-type mammalian brain.
Insights
Microvascular injury in the brain can trigger neuritic pathology and increase amyloidogenic potential. This study reveals a potential link between blood vessel damage and Alzheimer
Area of Science:
- Neuroscience
- Neuropathology
- Vascular Biology
Background:
- Microbleeds and neuritic plaques are common in aged brains, particularly in Alzheimer's disease (AD).
- The relationship between cerebral microvascular abnormalities and amyloid/neuritic pathology in AD is not fully understood.
- Investigating the causal link between vascular injury and amyloid pathogenesis is crucial for understanding AD progression.
Purpose of the Study:
- To explore the potential inductive effect of vascular injury on neuritic and amyloid pathogenesis.
- To investigate whether microvascular damage can initiate or exacerbate pathological changes relevant to AD.
- To examine the molecular changes in neurites and amyloid precursor proteins following experimental microvascular embolization.
Main Methods:
- Utilized a guinea pig model of cerebral microembolism to induce localized microvascular injury.
- Examined brain tissue 7-30 days post-embolization to assess pathological changes.
- Quantified glial fibrillary acidic protein (GFAP) immunoreactivity to detect astrogliosis around vasculature.
- Identified and characterized swollen/sprouting neurites using specific markers (e.g., nicotinamide adenine dinucleotide phosphate diaphorase, parvalbumin, vesicular glutamate transporter 1, choline acetyltransferase).
- Assessed the expression of beta-amyloid precursor protein (APP) and beta-secretase-1 (BACE1) in affected neurites.
Main Results:
- Experimental microvascular embolization led to increased GFAP immunoreactivity around intracortical vasculature.
- Swollen and sprouting neurites were observed in proximity to the embolized vasculature.
- These embolization-induced neurites showed increased reactivity for markers of neuronal damage and regeneration.
- Affected neurites were immunoreactive for beta-amyloid precursor protein (APP) and beta-secretase-1 (BACE1), key components of amyloidogenesis.
- These findings suggest that microvascular injury can trigger a cascade of pathological events in the brain.
Conclusions:
- Microvascular injury can induce multisystem neuritic pathology in the mammalian brain.
- Vascular damage is associated with an enhanced amyloidogenic potential, indicated by increased APP and BACE1 expression.
- These findings suggest a potential causal relationship between cerebrovascular abnormalities and the development of amyloid pathology, relevant to Alzheimer's disease.
- Targeting microvascular health may be a potential therapeutic strategy for neurodegenerative diseases like AD.
