P7C3-A20 treats traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis

by Selleckchem | Dec 31 2023

Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain. 3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine (P7C3-A20) can be neuroprotective in various diseases, including ischemic stroke and neurodegenerative diseases. However, whether P7C3-A20 has a therapeutic effect on traumatic brain injury and its possible molecular mechanisms are unclear. Therefore, in the present study, we investigated the therapeutic effects of P7C3-A20 on traumatic brain injury and explored the putative underlying molecular mechanisms. We established a traumatic brain injury rat model using a modified weight drop method. P7C3-A20 or vehicle was injected intraperitoneally after traumatic brain injury. Severe neurological deficits were found in rats after traumatic brain injury, with deterioration in balance, walking function, and learning memory. Furthermore, hematoxylin and eosin staining showed significant neuronal cell damage, while terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining indicated a high rate of apoptosis. The presence of autolysosomes was observed using transmission electron microscope. P7C3-A20 treatment reversed these pathological features. Western blotting showed that P7C3-A20 treatment reduced microtubule-associated protein 1 light chain 3-II (LC3-II) autophagy protein, apoptosis-related proteins (namely, Bcl-2/adenovirus E1B 19-kDa-interacting protein 3 [BNIP3], and Bcl-2 associated x protein [Bax]), and elevated ubiquitin-binding protein p62 (p62) autophagy protein expression. Thus, P7C3-A20 can treat traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis.

Comments:

The study you're summarizing suggests that P7C3-A20, a compound known for its neuroprotective properties in various neurological conditions, demonstrates therapeutic potential in treating traumatic brain injury (TBI) in rats. Here's a breakdown of the findings:

### Study Overview:
- **Method:** A TBI rat model was established using a modified weight drop method.
- **Intervention:** P7C3-A20 was administered intraperitoneally post-TBI compared to a control group receiving a vehicle.
- **Observations:**
- **Neurological Deficits:** Rats exhibited severe deficits in balance, walking function, and learning memory following TBI.
- **Neuronal Damage:** Hematoxylin and eosin staining showed significant neuronal cell damage, and terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining indicated a high rate of apoptosis.
- **Autolysosome Presence:** Transmission electron microscope observations suggested the presence of autolysosomes.
- **Treatment Effects:**
- P7C3-A20 treatment reversed the observed pathological features, indicating a therapeutic effect.
- **Molecular Mechanisms:**
- **Protein Expression Changes:** Western blot analysis revealed specific changes:
    - Reduced expression of microtubule-associated protein 1 light chain 3-II (LC3-II), associated with autophagy.
    - Decreased levels of apoptosis-related proteins (BNIP3, Bax).
    - Increased expression of the ubiquitin-binding protein p62 (p62), linked to autophagy.
- **Conclusion:** P7C3-A20 treatment appears to mitigate TBI in rats by inhibiting excessive autophagy and apoptosis.

### Significance:
- **Neuroprotective Potential:** P7C3-A20 demonstrates promise as a therapeutic agent for TBI by targeting cellular processes like autophagy and apoptosis that contribute to neuronal damage post-injury.
- **Implications:** The study's findings provide insights into potential molecular mechanisms underlying the neuroprotective effects of P7C3-A20 in TBI, opening avenues for further research and potential clinical applications.

This study sheds light on a potential treatment avenue for TBI, offering hope for therapeutic interventions to mitigate neuronal damage and improve outcomes following traumatic brain injuries.