Histidine enhances carbamazepine action against seizures and improves spatial memory deficits induced by chronic transauricular kindling in rats1

Abstract

Aim: To investigate whether histidine can enhance the anticonvulsant efficacy of carbamazepine (CBZ) and simultaneously improve the spatial memory impairment induced by transauricular kindled seizures in Sprague-Dawley rats. Methods: Chronic transauricular kindling was induced by repeated application of initially subconvulsive electrical stimulation through ear-clip electrodes once every 24 h until the occurrence of 3 consecutive clonic-tonic seizures. An 8-arm radial maze (4 arms baited) was used to measure spatial memory, and histamine and γ-aminobutyric acid levels were measured by high performance liquid chromatography (HPLC). Results: Chronic transauricular kindling produced a significant impairment of spatial memory and a marked decrease in histamine content in the hypothalamus, the brainstem, and the hippocampus. Injection of histidine (1000 mg/kg or 1500 mg/kg, ip) significantly inhibited transauricular kindled seizures. Injection of histidine at lower doses (200 mg/kg or 500 mg/kg, ip) had no appreciable anticonvulsant effect when administered alone, whereas it significantly potentiated the protective effects of CBZ against kindled seizures. CBZ had no ameliorative effect on memory deficit, but, in contrast, histidine (200 mg/kg or 500 mg/kg, ip) alone or co-administered with CBZ significantly ameliorated the memory deficits induced by the seizures. Conclusion: Chronic transauricular kindling is a very useful animal model for evaluating memory deficits associated with epilepsy, and histidine has both a potentiate effect on the anticonvulsant efficacy of CBZ and an ameliorative effect on the spatial memory deficits induced in this model. Histidine at a specific dosage range might serve as a beneficial adjuvant for the clinical treatment of epilepsy, especially when accompanied by impaired spatial memory.

Quartz crystal microbalance based histidine sensor

“…Additionally, histidine regulates metal ions transmission in biological systems and constitutes the active site of many enzymes and natural proteins [6,7]. Hence, excessive or deficiency of histidine/histidine rich proteins would cause many diseases like Parkinson's disease [2], epilepsy [8], histidinemia [9], chronic kidney disease [5], the failure of normal erythropoiesis development [10], inflammation and oxidative stress [5,11]. Sensitive, specific and accurate detection of histidine in biological samples has great significance in clinical analysis.…”

Modulation of the state of the antiepileptic cerebral system by the influence of a ketogenic diet under conditions of the resistant epileptic syndrome

“…Irradiation of the heads of experimental animals with millimeter electromagnetic waves also demonstrates greater antiepileptic efficacy. Finally, the use of histidine (the precursor of histamine [5,6]) is also more effective against the background of the KD. Under these conditions, the relative intensification of the effect of arginine (i.e., an agent also capable of suppressing the activity of epileptic foci [7]) is somewhat smaller.…”

A companion to the preclinical common data elements for rodent models of pediatric acquired epilepsy: A report of the TASK3‐WG1B, Pediatric and Genetic Models Working Group of the ILAE/AES Joint Translational Task Force

“…hippocampus or amygdala) to model human limbic seizures 36 . Electrical stimulation might also be applied to cornea or via ear clip topical electrodes [37][38][39] . Local electrical brain stimulation, like the stimulation of the perforant pathway, can also result in the induction of SE and may induce spontaneous seizures 40 .…”