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Updated: Mar 20, 2026
Controlled Cortical Impact Model for Traumatic Brain Injury
Published on: August 5, 2014
Activated brain mast cells contribute to postoperative cognitive dysfunction by evoking microglia activation and
Xiang Zhang1,2, Hongquan Dong1,2, Nana Li1,2
1Department of Anesthesiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People's Republic of China.
Background:
Neuroinflammation plays a key role in the occurrence and development of postoperative cognitive dysfunction (POCD). Microglia, the resident immune cells in the brain, has been increasingly recognized to contribute to neuroinflammation. Although brain mast cells (MCs) are the "first responder" in the brain injury rather than microglia, little is known about the functional aspects of MCs-microglia interactions.
Methods:
Male Sprague-Dawley (SD) rats were injected intracerebroventricular with MC stabilizer Cromolyn (100 μg/μl), MC stimulator C48/80 (1 μg/μl), or sterile saline 30 min before open tibial fracture surgery, and the levels of neuroinflammation and memory dysfunction were tested 1 and 3 days after surgery. In addition, the effect of activated MCs on microglia and neurons was determined in vitro.
Results:
Tibial fracture surgery induced MCs degranulation, microglia activation, and inflammatory factors production, which initiated the acute brain inflammatory response and neuronal death and exhibited cognitive deficit. Site-directed preinjection of the "MCs stabilizer" disodium cromoglycate (Cromolyn) inhibited this effect, including decrease of inflammatory cytokines, reduced MCs degranulation, microglia activation, neuronal death, and improved cognitive function 24 h after the surgery. In vitro study, we found that the conditioned medium from lipopolysaccharide (LPS)-stimulated mast cells line (P815) could induce primary microglia activation through mitogen-activated protein kinase (MAPK) pathway signaling and subsequent production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). In addition, the activated P815 could directly induce neuronal apoptosis and synapse injury with microglia independently. Cromolyn could inhibit P815 activation following improved microglia activation and neuronal loss.
Conclusions:
These results implicate that activated MCs could trigger microglia activation and neuronal damage, resulting in central nervous system (CNS) inflammation, and communications of MCs with microglia and neuron could constitute a new and unique therapeutic target for CNS immune inflammation-related diseases.
Insights
Activated mast cells (MCs) trigger microglia activation and neuronal damage, leading to central nervous system inflammation and cognitive dysfunction. Targeting MC-microglia communication offers a novel therapeutic strategy for neuroinflammatory diseases.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Neuroinflammation is critical in postoperative cognitive dysfunction (POCD).
- Microglia are key players in neuroinflammation.
- Mast cells (MCs), brain "first responders," have under-explored roles in neuroinflammation and interactions with microglia.
Purpose of the Study:
- To investigate the role of mast cells (MCs) in neuroinflammation and cognitive dysfunction following surgery.
- To elucidate the interaction between MCs and microglia in the central nervous system (CNS).
Main Methods:
- Rats received MC stabilizer (Cromolyn) or stimulator before surgery.
- Neuroinflammation and memory dysfunction were assessed post-surgery.
- In vitro studies examined activated MCs' effects on microglia and neurons.
Main Results:
- Surgery induced MC degranulation, microglia activation, and cognitive deficits.
- Cromolyn administration reduced inflammation, neuronal death, and improved cognitive function.
- Activated MCs induced microglia activation and neuronal apoptosis via MAPK signaling.
Conclusions:
- Activated MCs initiate CNS inflammation by activating microglia and causing neuronal damage.
- MCs-microglia-neuron communication represents a potential therapeutic target for CNS immune inflammation.
