• Modeling Mechanism：

  Oxidopamine hydrochloride, as a neurotoxin specific to dopaminergic neurons, induces PD pathology through multiple mechanisms: ① It is selectively taken up by dopamine transporters (DAT), generating large amounts of reactive oxygen species (ROS) within neurons, triggering oxidative stress damage; ② It disrupts mitochondrial function, activates apoptosis pathways, leading to progressive death of tyrosine hydroxylase (TH)-positive dopaminergic neurons in the substantia nigra pars compacta (SNc) of the midbrain; ③ It damages dopaminergic projection fibers in the medial forebrain tract (MFB), leading to striatal dopamine neurotransmitter depletion; simultaneously, as the disease progresses, it causes dysfunction of the hypothalamic orexin system, mimicking PD-related sleep disorders.

• Related Products：

  Oxidopamine hydrochloride (T12352)

• Modeling Method：

  Experimental Subject：

  Rats: Sprague Dawley (SD) strain, male, body weight 250–300 g

  Dosage and Administration Route：

  ① Core modelling: Oxidopamine (4 μg/μL) – dissolved in 0.2% ascorbic acid solution – bilateral two-point injection into the medial forebrain bundle (MFB) (coordinates: AP: 3.7/4.4 mm, ML: 1.7/1.2 mm, DV: 8.4/8.2 mm) – 6 μL injected per point;
  ② Surgical procedure: Intraperitoneal anaesthesia with sodium pentobarbital (40 mg/kg), stereotaxic fixation of head, microinjection via slow syringe injection after cranial drilling (avoiding backflow);
  ③ Control treatment: Equal volume of 0.2% ascorbic acid solution administered via identical injection protocol;
  ④ Model validation: From day 14 post-surgery, weekly intraperitoneal apomorphine injections (0.5 mg/kg) administered with rotational behaviour recorded; ≥7 revolutions per minute indicated successful model establishment

  Dosing Frequency and Duration Model：

  Single-dose Oxidopamine injection

• Validation：

  Pathological indicators: Neuronal degeneration: 7 days post-surgery, 62.0±6.2% of TH-positive neurons remained; 14 days later, this decreased to 24.5±3.5%; and 21 days later, only 2.1±0.4% remained. Orexin-A-positive neurons began to decrease at 21 days, decreased by 30% at 49 days (72.0±6.0% remaining), and showed no further decrease at 63 days. Behavioral indicators: Rats with successful modeling exhibited apomorphine-induced rotational behavior, accompanied by typical PD motor symptoms such as bradykinesia and rigidity. Molecular indicators: Cerebrospinal fluid orexin-A levels showed no significant fluctuations, and the density of orexin-A-positive fibers in the tuberous-papillary nucleus (TN) region did not decrease significantly. Specificity verification: The results conformed to the core characteristics of PD: "progressive loss of dopaminergic neurons - motor dysfunction - sleep-related neuropeptide system disorder," consistent with the pathological progression of clinical PD patients.

*Precautions： Cerebrospinal fluid collection should be performed at ZT 0 (with lights on) to avoid interfering with circadian rhythms.

*References：Cui LB,et,al. Progressive changes of orexin system in a rat model of 6-hydroxydopamine-induced Parkinson's disease. Neurosci Bull. 2010 Oct;26(5):381-7. doi: 10.1007/s12264-010-0410-9. Erratum in: Neurosci Bull. 2016 Jun 22;32(4):421.