• Modeling Mechanism：

  (-)-(α)-Kainic Acid (hydrate), as a glutamate receptor (mainly AMPA receptor) agonist, induces epilepsy pathology through multiple mechanisms: ① Overactivation of glutamate receptors in hippocampal CA1/CA3 neurons, leading to excitotoxicity, resulting in the death of a large number of pyramidal neurons and hippocampal structural damage (hippocampal sclerosis); ② Reduction of the number of NADPH-d positive neurons in hippocampal CA1 region, disrupting the nitric oxide (NO) signaling pathway, further exacerbating neuronal excitability imbalance; ③ Induction of interictal epileptiform discharges (sharp wave complexes) in local field potentials (LFP), accompanied by behavioral comorbidities such as anxiety and depression, mimicking the core pathological and clinical features of human TLE.

• Related Products：

  (-)-(α)-Kainic Acid (hydrate) (T37557)

• Modeling Method：

  Experimental Subject：

  Mouse, NMRI, Male, Adult, Body weight 30–35 g

  Dosage and Administration Route：

  ① Core modelling: KA (0.8 nmol/40 nL) dissolved in physiological saline, stereotaxic injection into left dorsal hippocampus (coordinates: posterior to anterior fontanelle - 1.6 mm, lateral to midline+1.6 mm, subdural - 1.2 mm);
  ② Surgical procedure: Ketamine (100 mg/kg)+Haloperidol (10 mg/kg) intraperitoneal anaesthesia; head fixed in stereotaxic apparatus; microinjection following cranial drilling (preventing solution reflux);
  ③ Control treatment: Isovolumetric saline solution administered via identical injection protocol;
  ④ Intervention verification (optional): 2-deoxy-D-glucose (2-DG, 300 mg/kg) intraperitoneal injection initiated 20 days post-modelling, once daily for 7 days

  Dosing Frequency and Duration Model：

  Single-dose KA injection

• Validation：

  Behavioral indicators: Motor and emotional states: In the open field test, the model group showed significantly increased movement distance and speed (P<0.05 vs. control group); in the sucrose preference test, the sucrose preference rate decreased (depressive-like behavior); in the zero maze test, the open arm dwell time increased and the first entry latency into the open arm shortened (anxiety-like behavior); 2-DG intervention could partially reverse depressive-like behavior; Electrophysiological indicators: Local field potential (LFP) recordings showed that the model group exhibited typical interictal epileptic-like discharges (sharp wave complexes, amplitude more than twice the baseline, frequency 1-20 Hz), while the control group did not show this discharge; Pathological indicators: Neuronal damage: Nissl staining showed a large loss of pyramidal neurons in the CA1 region of the hippocampus, reduced cell volume, and hippocampal structural damage; Molecular indicators: The number of NADPH-d positive neurons in the CA1 region of the hippocampus was significantly reduced (P<0.05 vs. control group), while the number of NADPH-d positive neurons in the contralateral hippocampus increased compensatorily; Cellular electrophysiology: Patch-clamp recordings showed that the model group had surviving CA1 neurons. The shortened neuronal membrane time constant (tau), decreased membrane capacitance, and increased spontaneous firing frequency (P<0.05 vs. control group) reflect enhanced neuronal excitability.

*Precautions： After the experiment was completed, the anesthetized animals were euthanized.

*References：Khatibi VA,et,al. The Glycolysis Inhibitor 2-Deoxy-D-Glucose Exerts Different Neuronal Effects at Circuit and Cellular Levels, Partially Reverses Behavioral Alterations and does not Prevent NADPH Diaphorase Activity Reduction in the Intrahippocampal Kainic Acid Model of Temporal Lobe Epilepsy. Neurochem Res. 2023 Jan;48(1):210-228.