• Modeling Mechanism：

  Bicuculline methochloride, as a competitive antagonist of γ-aminobutyric acid A (GABAₐ) receptors, induces epilepsy pathology through multiple mechanisms: ① It blocks GABAₐ receptor-mediated inhibitory synaptic transmission, disrupting the excitability/inhibition balance in the brain, triggering local neuronal overexcitation, and forming focal epileptic seizures; ② It induces hemodynamic changes (increased optical absorption coefficient) in the epileptic focus area, accompanied by abnormal interictal discharges on electroencephalography (EEG), mimicking the core pathological and electrophysiological characteristics of human neocortical epilepsy.

• Related Products：

  Bicuculline methochloride (T74112)

• Modeling Method：

  Experimental Subject：

  Rats: Sprague–Dawley (SD), male, adult, weight 240–260 g

  Dosage and Administration Route：

  ① Core modelling: Bicuculline methiodide (1.9 mM), 10 μL/animal, dissolved in saline, stereotaxic injection into right/left parietal cortex or specific brain regions (depth 1–3 mm, e.g., sensory cortex S1, caudate nucleus CPu) as single-dose administration;
  ② Surgical Procedure: Inhalation anaesthesia with isoflurane (4% induction, 1.5% maintenance)+intraperitoneal injection of propofol (1 g/kg). Head fixed in stereotaxic apparatus. Following removal of skull and scalp, microinjection performed at 0.3 μL/min using a microinjector;
  ③ Control procedure: Equal-volume saline administered via identical injection protocol;
  ④ Preparation for detection: Stainless steel screw electrodes implanted in the occipital bone as reference electrodes; DOT/ESL (Diffusion Optical Tomography/Electroencephalogram Source Localisation) probe adhered to cortical surface

  Dosing Frequency and Duration Model：

  Single dose

• Validation：

  Electrophysiological indicators: EEG recording: Typical epileptiform discharges (increased amplitude, abnormal frequency) appeared after modeling, lasting for more than 6 minutes, while no abnormal discharges were observed in the control group; Optical imaging: DOT detection showed a significant increase in the optical absorption coefficient of the epileptic focus area (P<0.05 vs. resting state), which could accurately locate epileptic foci with an injection depth of 1-3 mm. ESL was used for auxiliary verification, but there was a slight horizontal offset; Specificity verification: When Bicuculline methochloride was injected outside the field of view of the DOT/ESL probe, DOT showed a negative detection (no epileptic focus signal), and ESL may show false positives, confirming the specificity of DOT localization; Behavioral indicators: After modeling, focal limb twitching, stereotyped movements, and other focal epileptic seizure manifestations appeared, without generalized tonic-clonic seizures (consistent with the characteristics of focal epilepsy).

*Precautions： Animals were euthanized humanely in accordance with ethical requirements after the experiment. If long-term observation is required, the frequency of epileptic seizures should be monitored regularly, and euthanasia should be performed promptly if severe and persistent seizures occur.

*References：Yang H,et,al. In vivo imaging of epileptic foci in rats using a miniature probe integrating diffuse optical tomography and electroencephalographic source localization. Epilepsia. 2015 Jan;56(1):94-100.