Inflammation and Immune Mechanisms in the Central Nervous System

Inflammation and immune responses in the central nervous system (CNS) are the pathophysiological causes of many diseases. Inflammation and immune responses in the nervous system are complex and interplay among glial cells, peripheral immune cells and multiple kinds of mediators. When the interactions are abnormal, the blood-brain barrier (BBB) is damaged, neurons are injured, and neuroinflammation is initiated, the diseases progress. Due to the inaccessibility and complexity of the human nervous system, animal models are playing a critical role in the exploration of pathogenesis and the development of new drugs.

Creative Biolabs has built a high-end platform to meet the research demands of inflammation and immune mechanism in the CNS. Through applying the advanced technologies and utilizing the specific cellular and animal models, Creative Biolabs can support researchers and pharmaceutical companies from mechanism study to preclinical drug evaluation to promote the discovery of targeted therapies for neuroinflammatory diseases.

What Is CNS Inflammatory Disease?

Definition of CNS Inflammatory Diseases

Depending on the involved site, the CNS inflammatory diseases are encephalitis (parenchymal inflammation), meningitis (meningeal inflammation), and meningoencephalitis (mixed type). Depending on the etiology, they are infectious (viral/bacterial) and non-infectious (autoimmune/idiopathic) diseases.

Core Inflammatory Mechanisms

• Cytokine networks: Pro-inflammatory factors such as TNF-α and IL-1β amplify inflammation through the NF-κB and MAPK pathways, damaging the BBB
• Immune cell infiltration: Peripheral T cells breach the damaged BBB, recruiting macrophages to exacerbate myelin damage
• Antibody-mediated damage: For example, anti-NMDAR antibodies bind to neuronal surface receptors, disrupting synaptic function
• Granuloma formation: Macrophages/polymorphonuclear giant cells envelop blood vessels, causing lumen narrowing

Emerging Therapeutic Strategies

Targeting specific inflammatory pathways:

• Anti-cytokine monoclonal antibodies (e.g., anti-TNF-α)
• B-cell depletion therapy (e.g., anti-CD20 monoclonal antibodies)

miRNA Regulatory Networks in CNS Diseases

Functional Roles of miRNAs

Post-transcriptional regulation of gene expression is mediated by miRNAs, which inhibit mRNA translation and mediate neuroinflammation and apoptosis.

Table 1 Disease-associated miRNA dysregulation

Therapeutic Potential

• Diagnostic markers: Cerebrospinal fluid miRNA profiles can reflect neuroinflammatory status
• Therapeutic targets: Inhibit pro-inflammatory miRNAs (e.g., miR-155) or supplement protective miRNAs (e.g., miR-124a)

The Role of Microglia and Astrocytes in Neuroinflammation

Microglia and astrocytes serve crucial functions in neuroinflammation but exhibit differing roles and interactions across various diseases and pathologies.

Figure 1 Illustration of microglia and astrocyte.

Microglia in Neuroinflammation

Microglia are the innate immune cells of the central nervous system. The main functions of microglia are to receive environmental stimuli as receptors, phagocytose pathogens and dead cells, and regulate inflammatory reactions by secreting cytokines. In the process of neuroinflammation, microglia can be divided into pro-inflammatory microglia (M1) and neuroprotective microglia (M2). M1 microglia secrete pro-inflammatory factors, such as TNFα, IL-1β and MCP-1, while M2 microglia secrete anti-inflammatory factors, such as IL-10 and IL-4, which are neuroprotective. In the process of neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, etc.), abnormally activated microglia cause chronic inflammation, which exacerbates the damage of neurons. Microglia interact with astrocytes to regulate the intensity and duration of inflammation.

Astrocytes in Neuroinflammation

Astrocytes are the most common cell type in the central nervous system. Astrocytes play multiple roles including supporting neuronal metabolism, controlling neurotransmitter release, creating a blood-brain barrier and engaging in immune responses. In the process of neuroinflammation, astrocytes can be divided into neurotoxic (A1 phenotype) and neuroprotective (A2 phenotype). A1 astrocytes produce a large number of cytokines, nitric oxide synthase, etc., and enhance the inflammatory reaction. A2 astrocytes have anti-inflammatory and neuroprotective effects. In the process of neurodegenerative diseases, abnormal activation of astrocytes may form glial scar, blocking the recovery of neuronal function. Astrocytes can activate microglia by secreting chemokines (such as CCL2), and activate the inflammatory reaction.

Interactions in Neuroinflammation

Microglia and astrocytes also play an important role in neuroinflammation. Astrocytes release CCL2 to activate microglia which then shift into the M1 phenotype thus intensifying the inflammatory response. In addition, the cytokines released by microglia can regulate the activity of astrocytes and form a positive feedback loop.

Astrocytes have the ability to control inflammatory reactions by modulating how microglia cells become polarized.

In neuroinflammation both microglia and astrocytes serve dual functions as pro-inflammatory and neuroprotective cells whose specific roles depend on the disease stage as well as the inflammatory environment and interactions between cells.

Therapeutic Prospects and Challenges in CNS inflammation

Limitations of Current Therapies in CNS Inflammation

• Traditional immunosuppressants (such as glucocorticoids) lack specificity and have significant systemic side effects.
• Monoclonal antibodies have difficulty penetrating the BBB, resulting in low CNS delivery efficiency.

Emerging Directions in CNS Inflammation

Table 2 Examples of different emerging therapies

Application Prospect of Inflammatory miRNAs

miRNA, which is important for gene expression and immune regulation in the central nervous system, has the potential to be developed as a therapeutic agent and biomarker for neuroinflammatory diseases. miRNA can effectively modulate various signaling pathways that regulate inflammation, cell death, and neuronal survival, thus opening up new opportunities for precise and targeted control of neuroinflammatory responses. Inhibiting specific pro-inflammatory miRNAs such as miR-155 using targeted inhibitors can help to downregulate excessive inflammatory responses, prevent neuronal damage, and balance neuroinflammation. Supplementing neuroprotective miRNAs such as miR-124a can also promote tissue repair and healing and maintain a normal physiological state. With the improvement of blood-brain barrier penetration and targeted delivery strategies such as nanocarriers and viral vectors, miRNA-based therapies have become increasingly feasible. In addition, non-invasive biomarkers for early diagnosis, disease progression, and individualized treatment can be developed by detecting miRNA expression patterns in cerebrospinal fluid and blood. In conclusion, miRNAs provide a targeted, efficient and safer therapeutic intervention for neuroinflammatory diseases and have the potential to change the treatment paradigm.

Creative Biolabs is a leading CRO with extensive experience in a wide range of neurological disorders, including neuroinflammatory diseases and neurodegenerative diseases. Through our advanced cell and animal models, we assist researchers and pharmaceutical companies throughout the research process from mechanism studies to preclinical drug development.

Creative Biolabs is the right choice for CNS inflammation and immune mechanism research. Contact us today!

Reference

1. Ekkert, Aleksandra, et al."Inflammatory Disorders of the Central Nervous System Vessels: Narrative Review." Medicina, vol. 58, no. 10, Oct. 2022, p. 1446. DOI.org , https://doi.org/10.3390/medicina58101446.

Created June 2025

For Research Use Only. Not For Clinical Use.