Epilepsy syndromes during the early years of life may be attributed to an acquired insult, such as hypoxic-ischemic injury, infection, status epilepticus, or brain trauma. These conditions are frequently modeled in experimental rodents to delineate mechanisms of epileptogenesis and investigate novel therapeutic strategies. However, heterogeneity and subsequent lack of reproducibility of such models across laboratories is an ongoing challenge to maintain scientific rigor and knowledge advancement. To address this, as part of the TASK3-WG1B Working Group of the International League Against Epilepsy/American Epilepsy Society Joint Translational Task Force, we have developed a series of case report forms (CRFs) to describe common data elements for pediatric acquired epilepsy models in rodents. The "Rodent Models of Pediatric Acquired Epilepsy" Core CRF was designed to capture cohort-general information; while two Specific CRFs encompass physical induction models and chemical induction models, respectively. This companion manuscript describes the key elements of these models and why they are important to be considered and reported consistently. Together, these CRFs provide investigators with the tools to systematically record critical information regarding their chosen model of acquired epilepsy during early life, for improved standardization and transparency across laboratories. These outcomes will support the ultimate goal of such research; that is, to understand the childhood onset-specific biology of epileptogenesis after acquired insults, and translate this knowledge into therapeutics to improve pediatric patient outcomes and minimize the lifetime burden of epilepsy.

• Keywords
• brain injury, hypoxic ischemic injury, induction, infantile spasms, seizure, status epilepticus,
• MeSH
• Common Data Elements * MeSH
• Child MeSH
• Epilepsy * genetics   etiology   MeSH
• Rodentia MeSH
• Rats MeSH
• Humans MeSH
• Disease Models, Animal * MeSH
• Mice MeSH
• Advisory Committees MeSH
• Translational Research, Biomedical * methods   MeSH
• Animals MeSH
• Check Tag
• Child MeSH
• Rats MeSH
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

In spite of use of cannabidiol (CBD), a non-psychoactive cannabinoid, in pediatric patients with epilepsy, preclinical studies on its effects in immature animals are very limited. In the present study we investigated anti-seizure activity of CBD (10 and 60 mg/kg administered intraperitoneally) in two models of chemically induced seizures in infantile (12-days old) rats. Seizures were induced either with pentylenetetrazol (PTZ) or N-methyl-D-aspartate (NMDA). In parallel, brain and plasma levels of CBD and possible motor adverse effects were assessed in the righting reflex and the bar holding tests. CBD was ineffective against NMDA-induced seizures, but in a dose 60 mg/kg abolished the tonic phase of PTZ-induced generalized seizures. Plasma and brain levels of CBD were determined up to 24 h after administration. Peak CBD levels in the brain (996 ± 128 and 5689 ± 150 ng/g after the 10- and 60-mg/kg doses, respectively) were reached 1-2 h after administration and were still detectable 24 h later (120 ± 12 and 904 ± 63 ng/g, respectively). None of the doses negatively affected motor performance within 1 h after administration, but CBD in both doses blocked improvement in the bar holding test with repeated exposure to this task. Taken together, anti-seizure activity of CBD in infantile animals is dose and model dependent, and at therapeutic doses CBD does not cause motor impairment. The potential risk of CBD for motor learning seen in repeated motor tests has to be further examined.

• Keywords
• NMDA, PTZ, cannabidiol, epilepsy, immature rats, pentylentetrazole, seizures,
• MeSH
• Anticonvulsants pharmacology   MeSH
• Epilepsy drug therapy   MeSH
• Cannabidiol pharmacokinetics   pharmacology   MeSH
• Rats MeSH
• Disease Models, Animal MeSH
• Brain drug effects   MeSH
• N-Methylaspartate pharmacology   MeSH
• Pentylenetetrazole pharmacology   MeSH
• Rats, Wistar MeSH
• Seizures drug therapy   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anticonvulsants MeSH
• Cannabidiol MeSH
• N-Methylaspartate MeSH
• Pentylenetetrazole MeSH

The aim of our study was to reveal whether acute methamphetamine (MA) administration changes the sensitivity to seizures induced by N-methyl-D-aspartate (NMDA) in prenatally MA-exposed adult rats. Adult rats with respect to sex and female estrous cycle (prenatally MA-exposed, prenatally saline-exposed, and controls) were divided into groups with acute MA (1 mg/kg) or without acute drug administration (saline injection). Intraperitoneal administration of 250 mg/kg of NMDA was used as a seizure model. The present study demonstrated that both prenatal MA and prenatal saline exposure decreased the latency to onset of stereotypy and clonic-tonic seizures. Acute MA administration decreased latency to onset of stereotypic behavior in all groups, while increased latency to onset of clonic-tonic seizures in prenatally saline-exposed rats. The duration of NMDA seizures was longer after acute MA administration relative to animals without acute MA pretreatment in both control groups. In addition, males displayed decreased susceptibility to NMDA-induced seizures relative to females regardless of their estrous cycle. Our study suggests that acute MA exposure changes susceptibility to NMDA-induced seizures in respect of prenatal exposure and sex. However, it seems that the effect of prenatal exposure is not induced by the drug per se but rather by the repeated injection exposure that causes prenatal stress.

• MeSH
• Excitatory Amino Acid Agonists administration & dosage   toxicity   MeSH
• Time Factors MeSH
• Estrous Cycle physiology   MeSH
• Rats MeSH
• Methamphetamine pharmacology   MeSH
• N-Methylaspartate administration & dosage   toxicity   MeSH
• Rats, Wistar MeSH
• Drug Administration Schedule MeSH
• Sex Factors MeSH
• Stereotyped Behavior drug effects   MeSH
• Central Nervous System Stimulants pharmacology   MeSH
• Pregnancy MeSH
• Seizures chemically induced   MeSH
• Prenatal Exposure Delayed Effects MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Pregnancy MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Excitatory Amino Acid Agonists MeSH
• Methamphetamine MeSH
• N-Methylaspartate MeSH
• Central Nervous System Stimulants MeSH