Brain health

Thema:
Efficient drug development

Brain health is determined by interactions between metabolism, vascular function, inflammation and ageing. Disturbances in these interconnected processes can contribute to changes in brain structure and function, which can be studied with TNO’s technologies and in vivo models. TNO’s proprietary Ldlr-/-.Leiden mouse model provides a translational platform to study brain health in the context of ageing and metabolic dysfunction. On a standard chow diet, the model develops key features of age-related brain impairment. A high-fat diet induces obesity, insulin resistance and chronic low-grade inflammation, accelerating changes in brain structure and function. Depending on the research question, studies can integrate behavioural and cognitive testing, quantitative brain histopathology, MRI, blood-brain barrier permeability, transcriptomics, proteomics, lipidomics, oxylipin profiling and spatial mass-spectrometry imaging. This integrated body-brain approach supports efficacy testing, mechanism-of-action studies and biomarker development for pharmaceutical and nutritional interventions.

Key capabilities

Study types

Tailor-made efficacy studies for targeted pathways and mechanisms

Models

Ldlr-/-.Leiden mice in an aging or obesity context

Output

Integrated structural, functional and molecular readouts across body and brain

A powerful approach to accelerate brain research

TNO combines a translational model of metabolic dysfunction with complementary brain readouts to evaluate whether and how an intervention affects brain health. The Ldlr-/-.Leiden model captures obesity-associated and ageing-related processes, including neuroinflammation, vascular and blood-brain barrier dysfunction, impaired white matter integrity, oxidative stress and altered brain energy metabolism. Study designs are tailored to the target, biological hypothesis and development stage. By connecting in-life outcomes with regional histopathology, advanced imaging and multi-omics, we generate robust datasets that support early go/no-go decisions and provide mechanistic context for observed treatment effects.

AI-powered histopathology

Our AI-supported histopathology platform enables standardised, fast, and high-throughput analysis of brain tissue cross-sections. Digitised sections are delineated into anatomical regions, allowing accurate quantification of neuronal and glial cell (astocytes, microglica) markers as well as morphological analyses such as cortical thickness. The platform can be applied to both TNO-generated and externally generated histology samples.

Use cases

Drug efficacy testing

Evaluate whether interventions prevent, slow or reverse ageing- or dysmetabolism-associated changes in brain structure, function and inflammation.

Mechanism of action studies

Investigate how compounds influence neuroinflammatory pathways, glial immunophenotypes, mitochondrial function/oxidative stress, blood-brain barrier integrity, white matter integrity and neuronal health.

Biomarker development

Support biomarker discovery and generate translational evidence linking preclinical findings to human brain biology.

Spatial drug distribution and response

Use MALDI mass-spectrometry imaging to map drug uptake and distribution and combine this with spatial response readouts (histology or lipidomics/metabolomics).

A tailored path to translational insights

  • Study design

    Step 1

    We collaborate to define a study tailored to your compound, research questions, and selected endpoints, ensuring a clear and relevant experimental setup.

  • In-life phase

    Step 2

    The study is executed with compound administration (e.g. diet, PO, SC, IP, IV) under controlled conditions, including regular monitoring and interim data readouts.

  • Analysis

    Step 3

    We offer extensive efficacy and mechanistic readouts, combining expert pathological assessment with AI driven image analysis, alongside biochemistry, imaging, and omics.

  • Reporting

    Step 4

    We tailor the delivery of results to your needs, from data delivery to a comprehensive report with expert interpretation and recommendations for next steps.

Choose the right preclinical research partner

  • Translational model that connects metabolic dysfunction with ageing- and obesity-related brain pathology
  • Expertise and technologies that allow assessment of brain structure, function, inflammation, vascular integrity and molecular mechanisms
  • Ethical and responsible research execution
  • Clear, actionable data to support informed development decisions

Ready to accelerate your brain research?

Get in touch to discuss your research question and explore how TNO can design and execute a tailored preclinical brain health study for your compound. In an initial discussion, we:

  • will align on your target biology, development question and intended patient context
  • propose a suitable age, diet condition, study design and intervention window
  • select fit-for-purpose structural, functional and molecular endpoints
  • provide a first study outline and indicative cost range