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Updated: Aug 23, 2025
Controlled Cortical Impact Model for Traumatic Brain Injury
Published on: August 5, 2014
Traumatic Brain Injury-Mediated Neuroinflammation and Neurological Deficits are Improved by 8-Methoxypsoralen Through
Yuzuo Hui1, Han Zhao2, Lei Shi3
1Department of Neurosurgery, Liaocheng People's Hospital, 67 Dongchang Road, Liaocheng, 252000, Shandong, China.
Abstract:
8-Methoxypsoralen (8-MOP) has anti-inflammatory, antioxidant and tissue-repairing abilities. Here, we probed the function and mechanism of 8-MOP in traumatic brain injury (TBI). The in-vivo TBI model was constructed in Sprague-Dawley (SD) rats using controlled cortical impact (CCI) surgery. In parallel, BV2 microglia and HT22 neurons were activated by lipopolysaccharide (LPS) to establish an in-vitro model. The modified neurological score (mNSS) and the Morris water maze experiment were employed to evaluate the rats' neurological functions. The rats' brain edema was assessed by the dry and wet method, and neuronal apoptosis in damaged brain tissues was monitored by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and Nissl's staining. Immunohistochemistry (IHC) was applied to verify Iba1-microglial activation in brain lesions of rats. The expression of inflammatory cytokines in BV2 microglia and HT22 neurons in the injured lesion of TBI rats was examined by the enzyme-linked immunosorbent assay (ELISA). The levels of iNOS, COX2, TLR4, PPARγ, STAT3, and NF-κB in brain lesions, BV2 microglia and HT22 neurons were compared by Western blot. As a result, 8-MOP administration reduced inflammation and LPS-induced neuronal damage in BV2 microglia. In vivo, 8-MOP treatment relieved neurological deficits in TBI rats, improved cognitive, learning and motor functions and mitigated brain edema and neuroinflammation induced by TBI. Furthermore, LPS or TBI activated the NF-κB and STAT3 pathways and repressed the PPARγ expression. However, 8-MOP treatment attenuated NF-κB and STAT3 phosphorylation and elevated PPARγ levels. Hence, 8-MOP exerts neuroprotective and anti-inflammatory effects in TBI rats by modulating the PPARγ/NF-κB pathway.
Insights
8-Methoxypsoralen (8-MOP) reduces inflammation and brain damage after traumatic brain injury (TBI). This study shows 8-MOP protects neurons by modulating the PPARγ/NF-κB pathway, improving neurological function in TBI rats.
Area of Science:
- Neuroscience
- Pharmacology
- Inflammation Research
Background:
- Traumatic brain injury (TBI) is a significant cause of neurological damage.
- 8-Methoxypsoralen (8-MOP) exhibits anti-inflammatory and antioxidant properties.
- The therapeutic potential of 8-MOP in TBI requires further investigation.
Purpose of the Study:
- To investigate the neuroprotective and anti-inflammatory mechanisms of 8-MOP in a rat model of TBI.
- To elucidate the role of the PPARγ/NF-κB pathway in 8-MOP's therapeutic effects.
Main Methods:
- Established in vivo TBI model using controlled cortical impact (CCI) in Sprague-Dawley rats.
- Utilized in vitro models with BV2 microglia and HT22 neurons stimulated by lipopolysaccharide (LPS).
- Assessed neurological function, brain edema, neuronal apoptosis, microglial activation, and inflammatory cytokine expression.
- Analyzed protein levels of iNOS, COX2, TLR4, PPARγ, STAT3, and NF-κB via Western blot.
Main Results:
- 8-MOP reduced inflammation and LPS-induced neuronal damage in vitro.
- In vivo, 8-MOP treatment improved neurological deficits, cognitive, learning, and motor functions in TBI rats.
- 8-MOP mitigated TBI-induced brain edema and neuroinflammation.
- 8-MOP modulated the PPARγ/NF-κB pathway by attenuating NF-κB and STAT3 phosphorylation and increasing PPARγ levels.
Conclusions:
- 8-Methoxypsoralen (8-MOP) demonstrates significant neuroprotective and anti-inflammatory effects in a TBI model.
- The therapeutic mechanism involves the modulation of the PPARγ/NF-κB signaling pathway.
- 8-MOP holds promise as a potential therapeutic agent for managing TBI.
