Effects of recurrent ketamine exposure on brain histopathology in juvenile rats. 2023

Ayşe Hande Arpacı, and Süheyla Esra Özkoçer, and Emel Güneş, and Çiğdem Elmas, and Berrin Işık
Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Ankara University, Ankara, Turkey.

BACKGROUND Ketamine (KET) is a commonly used anesthetic agent. However, several previous studies reported that KET leads to neuronal damage in neurodevelopmental stages and has neuroprotective effects. The present experimental study aimed to determine the undesirable histopathological effects of KET in the cerebral cortex, striatum, and hippocampus after recurrent KET administration in juvenile rats. METHODS After ethical approval was obtained, 32 juvenile male Wistar Albino rats were randomized into four groups: 1 mg/kg serum saline intraperitoneally (i.p.), 5 mg/kg KET i.p., 20 mg/kg KET i.p., and 50 mg/kg KET i.p. KET was administered for three consecutive days at three-h intervals in three doses. Ten days after the last KET dose, the rats were sacrificed. Cerebral hemispheres were fixed. Hematoxylin and eosin stain was used for morphometric analysis. Hippocampi were evaluated by immunohistochemistry with anticleaved caspase-3 antibodies. Statistical analysis was conducted with SPSS 21 software using the ANOVA test and Bonferroni post hoc analysis method. RESULTS The experimental study findings revealed no difference between the groups' cell counts or sizes in cortical morphometry. No degenerative changes were observed in pyramidal and granular cells in the striatum. Mild gliosis was observed in the 20 mg/kg and 50 mg/kg KET administration groups. Immuno-histo-chemical analysis was conducted to determine apoptosis in the CA1 region of the hippocampus and revealed that caspase-3 positivity increased with the KET dose. However, there was no statistical difference between the groups. While it was lower than the control group in the 5 mg/kg KET group, it was similar to the control group in the 20 mg/kg KET group and higher in the 50 mg/kg KET group (p > 0.05). CONCLUSIONS : Repetitive KET exposure did not significantly affect juvenile cerebral morphology and apoptosis in hippocampal cells.

UI MeSH Term Description Entries
D007649 Ketamine A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors. 2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone,CI-581,Calipsol,Calypsol,Kalipsol,Ketalar,Ketamine Hydrochloride,Ketanest,Ketaset,CI 581,CI581
D008297 Male Males
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D053148 Caspase 3 A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA. CASP3,Apopain,Caspase-3,Pro-Caspase-3,Procaspase-3,Pro Caspase 3,Procaspase 3

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