BBB integrity is essential for brain health but can be disrupted by disease or drug action. This in vivo assay helps assess whether your compound compromises the barrier—or restores it after damage from stroke, neurodegeneration, or aging.
(On the left) Pseudocolor image showing the progression of blood-brain barrier leakiness from cortical vessels into surrounding brain parenchyma. 2-photon data obtained at Neurotar.
How a drug reaches the brain matters
Does your compound carry a key (active transport) or force the door open (by compromising the barrier)? Neurotar’s team can visualize these processes in vivo. We can also assess whether your drug helps repair a leaky blood-brain barrier—damaged by stroke, aging, neurodegeneration, or other conditions.
Why use two-photon microscopy for BBB integrity studies?
In vitro assays fall short when it comes to mimicking the full complexity of the blood–brain barrier. in vivo two-photon imaging, by contrast, offers high-resolution views of the cortical tissue—making it possible to clearly distinguish vascular from parenchymal compartments. It also allows us to induce localized BBB disruption, such as in a microstroke model.
Key advantages:
• High-resolution imaging distinguishes vascular vs. parenchymal compartments
• Performed in the brains of living mice
• Low phototoxicity supports longitudinal imaging (days to months)
• The mouse serves as its own control, boosting statistical power
• Two-photon laser can be used to disrupt the BBB in a controlled manner
How we measure BBB integrity
We inject fluorescently labeled dextrans intravenously—typically 70 kDa (albumin-sized) and smaller variants (3–40 kDa). Two-photon imaging allows ratiometric analysis of their distribution, revealing BBB leakiness associated with aging, disease, or treatment.
What BBB integrity studies can Neurotar perform for you?
We use wild-type mice to evaluate whether your lead compound compromises BBB integrity in an otherwise healthy brain.
We work with senile mice and transgenic models (e.g., AD, PD) that develop BBB abnormalities over time—to test whether your compound can prevent or delay barrier breakdown.
Using a two-photon laser, we induce localized BBB disruption in wild-type mice. We then assess whether your compound can prevent the damage and/or promote recovery.
Image above: Laser-induced microstroke causing localized disruption of blood-brain barrier integrity (before stroke – left; after stroke – right)
How can Neurotar support candidate selection?
Neurotar is the world’s leading commercial provider of in vivo two-photon brain imaging in mice.
We start by discussing your research goals and identifying the most relevant models to evaluate BBB disruption or restoration.
We assist in selecting the right wild-type or transgenic models and help source animals and licenses from trusted providers.
We guide you in choosing optimal delivery routes—oral (gavage), i.p., s.c., i.v., intrathecal (i.t.), or Cisterna Magna injection.
Following dextran injection, we image the same cortical region over time to quantify BBB permeability. We can also induce localized disruption using a microstroke model if required.
At study completion, we can collect and preserve tissue samples for downstream analysis—either in your lab or via your partner CRO.
We present and interpret results, recommend next steps, and finalize the report based on your input.
If you plan to publish or present the findings, we can help draft abstracts, posters, investor decks, or manuscripts.
Relevant publications:
Shi L., Palacio-Mancheno P., Badami J., Shin D.W., Zeng M., Cardoso L., Tu R., Fu B.M. (2014) Quantification of transient increase of the blood-brain barrier permeability to macromolecules by optimized focused ultrasound combined with microbubbles. Int. J. Nanomed. 9:4437–4448. DOI: 10.2147/IJN.S68882
Biancardi V. C., Son S. J., Ahmadi S., Filosa J. A., and Stern J. E. (2014) Circulating angiotensin II gains access to the hypothalamus and brain stem during hypertension via breakdown of the blood‐brain barrier. Hypertension 63:572–579. DOI:10.1161/HYPERTENSIONAHA.113.01743.
Burgess A., Nhan T., Moffatt C., Klibanov A.L., Hynynen K. (2014) Analysis of focused ultrasound-induced blood-brain barrier permeability in a mouse model of Alzheimer’s disease using two-photon microscopy. J. Control. Release. 192:243–248. DOI:10.1016/j.jconrel.2014.07.051.
Other two-photon brain imaging services offered by Neurotar
| Neurodeg. Disease (e.g. AD, PD) | Stroke and TBI | Neuropathic Pain and Migraine | Neuropsychiatry (e.g. Schizophrenia) | Epilepsy | |
|---|---|---|---|---|---|
| Blood-brain barrier integrity | ✓ | ✓ | ✓ | ||
| Trans-BBB pharmacokinetics | ✓ | ✓ | ✓ | ||
| Dendritic spine turnover | ✓ | ✓ | ✓ | ✓ | ✓ |
| Microglial dynamics or response to injury | ✓ | ✓ | ✓ | ✓ | ✓ |
| Calcium signaling | ✓ | ✓ | ✓ | ✓ | ✓ |
| Abeta Plaque or Tau Tangle dynamics | ✓ | ✓ | ✓ | ||
| Mitochindria dysfunction | ✓ | ✓ | ✓ | ✓ | ✓ |
| Ischemic Stroke model | ✓ | ||||
| Regeneration of peripheral neurons | ✓ | ✓ | ✓ |