Repeated acetaminophen administration damaged hippocampal tissue but did not affect prefrontal cortex or anxiety behaviors.

Acetaminophen is one of the most widely used over­the­counter drugs worldwide for the treatment of pain and fever. Although acetaminophen use is known to impair hippocampus­related learning and memory, its effect on anxiety is not clear. Insulin­like growth factor­1 (IGF­1) and matrix metalloproteinase­2 (MMP2) are important for cellular survival, maintenance and tissue integrity. The aim of this study was to investigate the dose­dependent effects of acetaminophen on anxiety levels as well as on hippocampus, prefrontal cortex and liver tissue. Doses of 100, 200 and 400 mg/kg acetaminophen were administered to male Sprague Dawley rats for 11 days and anxiety tests were conducted on the last day. Twenty­four hours after the last acetaminophen administration, all animals were sacrificed and hippocampus, prefrontal cortex and liver tissues were removed for analyses. Hippocampal IGF­1 and MMP2 levels were shown to decrease only at the highest dose of acetaminophen, which was accompanied by pathological changes in histology. The prefrontal cortex was not affected. Behavioral analyses also did not indicate changes in anxiety levels in the rats. Liver IGF­1 and MMP2 levels decreased in all experimental groups. Serum alanine aminotransferase and aspartate aminotransferase levels increased in the 200 mg/kg and 400 mg/kg acetaminophen groups. Our findings showed that varying doses of acetaminophen did not affect the prefrontal cortex or anxiety levels. Further research is needed to elucidate the hippocampal and hepatic protective roles of IGF­1 and MMP2 in acetaminophen toxicity and their potential use in therapeutic approaches.

Validity and reliability of "Cognitive Reserve Index Questionnaire" for the Turkish Population.

BACKGROUND: Cognitive reserve (CR) is the ability to counteract brain damage through differential recruitment of brain networks. Besides, it has also been observed that lifetime intellectual enriching skills reduce the effect of disease burden on cognitive status. The Cognitive Reserve Index questionnaire (CRIq), which is a method for the quantitative measurement and comprehensive evaluation of the CR, that individuals have accumulated throughout their lifetimes. The present study aimed to adapt CRIq to the Turkish population. METHODS: CRIq is a 20-item questionnaire consisting of 3 sub-scales (CRI-Education, CRI- Working Activity, CRI-Leisure Time). 271 females and 228 males, a total of 499 healthy volunteers participated in the study (mean age: 39.54±14.05, mean education years 13.14±4.84). Participants were evaluated with the "Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS)" and CRIq was applied. BICAMS was used to determine the validity of the CRIq. To determine the reliability, the questionnaire was applied again two weeks after the first application. Internal consistency and test-retest reliability were measured for reliability analysis. Independent sample t-test was conducted to observe the difference between genders. RESULTS: The Cronbach alpha coefficient of the questionnaire was 0.78, and the reliability of the questionnaire was acceptable. The findings showed that inter-rater reliability was quite high (ICC:0.95, 95% CI=1.000, n=36). The correlation between the first and second application of the questionnaire was found to be acceptable for both the sub-scales and the whole questionnaire. The highest CRIq scores were shown for young adults in CRI-Education and CRI-LeisureTime, for the middle-aged in CRIq-WorkingActivity, no significant differences in total CRIq scores. The males scored significantly higher in CRIq total scores than females, but there was not a significant difference in CRI-LeisureTime between genders. CONCLUSION: The Turkish version of CRIq was found to be a valid and reliable method for evaluating cognitive reserve in healthy individuals.

Stem Cell Therapy for Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory, autoimmune, and neurodegenerative disease of the central nervous system (CNS). It is characterized by demyelination and neuronal loss that is induced by attack of autoreactive T cells to the myelin sheath and endogenous remyelination failure, eventually leading to functional neurological disability. Although recent evidence suggests that MS relapses are induced by environmental and exogenous triggers such as viral infections in a genetic background, its very complex pathogenesis is not completely understood. Therefore, the efficiency of current immunosuppression-based therapies of MS is too low, and emerging disease-modifying immunomodulatory agents such as fingolimod and dimethyl fumarate cannot stop progressive neurodegenerative process. Thus, the cell replacement therapy approach that aims to overcome neuronal cell loss and remyelination failure and to increase endogenous myelin repair capacity is considered as an alternative treatment option. A wide variety of preclinical studies, using experimental autoimmune encephalomyelitis model of MS, have recently shown that grafted cells with different origins including mesenchymal stem cells (MSCs), neural precursor and stem cells, and induced-pluripotent stem cells have the ability to repair CNS lesions and to recover functional neurological deficits. The results of ongoing autologous hematopoietic stem cell therapy studies, with the advantage of peripheral administration to the patients, have suggested that cell replacement therapy is also a feasible option for immunomodulatory treatment of MS. In this chapter, we overview cell sources and applications of the stem cell therapy for treatment of MS. We also discuss challenges including those associated with administration route, immune responses to grafted cells, integration of these cells to existing neural circuits, and risk of tumor growth. Finally, future prospects of stem cell therapy for MS are addressed.