Preclinical Assessment of a New Hybrid Compound C11 Efficacy on Neurogenesis and Cognitive Functions after Pilocarpine Induced Status Epilepticus in Mice

• Published in: International journal of molecular sciences Vol. 22; no. 6; p. 3240
• Main Authors: Andres-Mach, Marta, Szewczyk, Aleksandra, Zagaja, Mirosław, Szala-Rycaj, Joanna, Lemieszek, Marta Kinga, Maj, Maciej, Abram, Michał, Kaminski, Krzysztof
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 22.03.2021; MDPI AG
• Subjects: Animals; anticonvulsant; Anticonvulsants - administration & dosage; Anticonvulsants - pharmacology; antiepileptic drugs; Astrocytes - drug effects; Astrocytes - metabolism; Biomarkers; Cognition - drug effects; Disease Models, Animal; Drug Evaluation, Preclinical; Hippocampus - drug effects; Hippocampus - metabolism; Male; Mice; neurogenesis; Neurogenesis - drug effects; neuroprotection; Neuroprotective Agents - pharmacology; pilocarpine; Pilocarpine - adverse effects; Status Epilepticus - diagnosis; Status Epilepticus - drug therapy; Status Epilepticus - etiology; pilocarpine; neurogenesis; antiepileptic drugs; anticonvulsant; neuroprotection
• DOI: 10.3390/ijms22063240
• ISSN: 1422-0067; 1661-6596

Status epilepticus (SE) is a frequent medical emergency that can lead to a variety of neurological disorders, including cognitive impairment and abnormal neurogenesis. The aim of the presented study was the evaluation of potential neuroprotective properties of a new pyrrolidine-2,5-dione derivatives compound C11, as well as the assessment of the impact on the neurogenesis and cognitive functions of C11 and levetiracetam (LEV) after pilocarpine (PILO)-induced SE in mice. The results indicated a protective effect of C11 (500, 1000, and 2500 ng/mL) on astrocytes under trophic stress conditions in the MTT (3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide) test. The results obtained from the studies, where mice 72 h after PILO SE were treated with C11 (20 mg/kg) and LEV (10 mg/kg), indicated markedly beneficial effects of C11 on the improvement of the neurogenesis compared to the PILO control and PILO LEV mice. Moreover, this beneficial effect was reflected in the Morris Water Maze test evaluating the cognitive functions in mice. The confirmed protective effect of C11 on astrocytes, as well as the demonstrated beneficial impact on neurogenesis and cognitive functions, strongly indicate the need for further advanced molecular research on this compound to determine the exact neuroprotective mechanism of action of C11.