• Modeling Mechanism：

  Colchicine, as a microtubule disruptor, induces Alzheimer's disease-like pathology through multiple mechanisms: ① It irreversibly binds to tubulin, inhibiting microtubule assembly and axoplasmic transport, damaging the neuronal cytoskeleton, and leading to the death of cholinergic neurons in the hippocampus and basal forebrain; ② It induces oxidative stress, increasing levels of reactive oxygen species (ROS) and nitric oxide (NO), promoting lipid peroxidation (increased MDA), and depleting the endogenous antioxidant system (decreased activity of GSH, SOD, CAT, etc.); ③ It upregulates acetylcholinesterase (AChE) activity, reduces the content of acetylcholine (ACh) in the brain, interferes with cholinergic neurotransmission, and ultimately leads to cognitive dysfunction.

• Related Products：

  Colchicine (T0320)

• Modeling Method：

  Experimental Subject：

  Rats, Wistar, Male, Body weight 180–200 g

  Dosage and Administration Route：

  ① Core modelling: Colchicine (15 μg/5 μL) dissolved in artificial cerebrospinal fluid (ACSF), intraventricular (ICV) injection into lateral ventricle;
  ② Surgical procedure: Intraperitoneal anaesthesia with thiopental sodium (45 mg/kg), stereotaxic fixation of head, cranial drilling coordinates: 0.8 mm posterior to anterior fontanelle, 1.8 mm lateral to sagittal suture, 3.6 mm subcortical depth; microinjection syringe injection (needle retained for 2 minutes to prevent reflux);
  ③ Control procedure: equal-volume ACSF intraventricular injection via identical method;
  ④ Intervention validation (optional): Centella asiatica extract (CA, 150/300 mg/kg) administered via gastric lavage

  Dosing Frequency and Duration Model：

  Single-dose colchicine injection
  Intervention validation commenced 4 days prior to modelling and continued for 25 days

• Validation：

  Behavioral indicators: Cognitive function: Morris water maze showed an increased initial learning latency (IAL) of 88.0±1.93 seconds in the model group (55.33±1.7 seconds in the ACSF group, P<0.05), and the retention latency was still significantly increased at 21 days (62.33±1.80 seconds); in the elevated cross maze, the retention transfer latency (RTL) of the model group was significantly prolonged (72.33±1.20 seconds vs. 12.60±1.49 seconds in the ACSF group, P<0.05), confirming memory acquisition and retention impairment; Motor function: There was no significant change in spontaneous activity count, excluding interference from motor ability; Biochemical indicators: Oxidative stress: The levels of MDA (339.88±32% of sham) and nitrite (298.39±15% of sham) in the brain were significantly increased, and GSH (23.38±10% of sham) was significantly increased. The activities of sham, SOD (13.47±3% of sham), and CAT (17.98±8% of sham) were significantly reduced (P<0.05); Cholinergic function: Acetylcholinesterase (AChE) activity was significantly increased, and intervention with Centella asiatica could reverse the effect in a dose-dependent manner; Specificity verification: The model phenotype was consistent with the core characteristics of sporadic AD, namely "cognitive impairment-oxidative stress-cholinergic damage", and antioxidants (such as Centella asiatica extract) could improve pathological indicators.

*Precautions： Monitor the postoperative recovery of rats during the modeling period. Rats with infection or severe behavioral abnormalities should be culled promptly.

*References：Kumar A,et,al. Neuroprotective Effects of Centella asiatica against Intracerebroventricular Colchicine-Induced Cognitive Impairment and Oxidative Stress. Int J Alzheimers Dis. 2009 Sep 13;2009:972178.