• Modeling Mechanism：

  Rotenone, as an inhibitor of mitochondrial complex I, induces PD pathology through multiple mechanisms: ① It selectively inhibits the activity of mitochondrial complex I in dopaminergic neurons of the substantia nigra pars compacta (SNc), reducing ATP production and causing structural damage such as mitochondrial swelling and cristae breakage; ② It promotes the excessive production of reactive oxygen species (ROS), inducing oxidative stress and damaging lipids, proteins, and DNA; ③ It activates the apoptosis pathway, upregulating the expression of the pro-apoptotic protein Bax and downregulating the expression of the anti-apoptotic protein Bcl-XL, leading to the death of SNc dopaminergic neurons; ④ It inhibits the activity of vesicular monoamine transporter 2 (VMAT2), increasing cytoplasmic dopamine accumulation and exacerbating neurotoxicity.

• Related Products：

  Rotenone (T2970)

• Modeling Method：

  Experimental Subject：

  Rats: Wistar strain, male, 6 weeks old, body weight 200–250 g

  Dosage and Administration Route：

  ① Core modelling: Rotenone (2 mg/kg/day) dissolved in soybean oil administered subcutaneously (SC);
  ② Control treatment: equal volume soybean oil administered via same route;
  ③ Intervention validation (optional): Edaravone (10 mg/kg/day) dissolved in physiological saline, administered intraperitoneally (IP) in two divided doses (7:00 am and 7:00 pm), initiated concurrently with modelling and continued for 5 weeks

  Dosing Frequency and Duration Model：

  Rotenone injection once daily for 5 weeks

• Validation：

  Behavioral indicators: Motor function: 81% (22/27 animals) of the model group showed typical PD symptoms (kyphosis, stiffness, bradykinesia), and the fall latency in the grid test and bar test was significantly prolonged (P<0.05 vs control group); edaravone intervention could shorten the latency by more than 85%; Pathological indicators: Neuronal damage: SNc tyrosine hydroxylase (TH) positive neurons decreased by 60.48%, and striatum (CPu) TH immunostaining intensity decreased by 65.67%; edaravone intervention could salvage 44.66% of dopaminergic neurons; Mitochondrial damage: Transmission electron microscopy showed mitochondrial swelling, cristae breakage, and vacuolar degeneration in SNc neurons; edaravone intervention could significantly improve mitochondrial structure; Molecular indicators: Oxidative stress: Midbrain ROS levels were significantly increased; edaravone could inhibit 73.35% of ROS generation; Apoptosis-related: Bax protein expression was upregulated, Bcl-XL... Downregulation of expression can be reversed by edaravone; Transporter expression: VMAT2 mRNA and protein levels are reduced, and edaravone can upregulate their expression by 45%-70%.

*Precautions： After the behavioral test, the rats were euthanized and their midbrains were micro-perforated. Intracellular ROS levels were then measured.

*References：Xiong N,et,al. Edaravone guards dopamine neurons in a rotenone model for Parkinson's disease. PLoS One. 2011;6(6):e20677.