scholarly journals Acute pre-operative ibuprofen improves cognition in a rat model for postoperative cognitive dysfunction

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Klaske Oberman ◽  
Iris Hovens ◽  
Jacco de Haan ◽  
Joana Falcao-Salles ◽  
Barbara van Leeuwen ◽  
...  

Abstract Background Inflammation is considered a key factor in the development of postoperative cognitive dysfunction (POCD). Therefore, we hypothesized that pre-operative anti-inflammatory treatment with ibuprofen would inhibit POCD in our rat-model. Methods Male Wistar rats of 3 or 23 months old received a single injection of ibuprofen (15 mg/kg i.p.) or were control handled before abdominal surgery. Timed blood and fecal samples were collected for analyses of inflammation markers and gut microbiome changes. Behavioral testing was performed from 9 to 14 days after surgery, in the open field, novel object- and novel location-recognition tests and Morris water maze. Neuroinflammation and neurogenesis were assessed by immune histochemistry after sacrifice on postoperative day 14. Results Ibuprofen improved short-term spatial memory in the novel location recognition test, and increased hippocampal neurogenesis. However, these effects were associated with increased hippocampal microglia activity. Whereas plasma cytokine levels (IL1-β, IL6, IL10, and TNFα) were not significantly affected, VEGF levels increased and IFABP levels decreased after ibuprofen. Long-term memory in the Morris water maze was not significantly improved by ibuprofen. The gut microbiome was neither significantly affected by surgery nor by ibuprofen treatment. In general, effects in aged rats appeared similar to those in young rats, though less pronounced. Conclusion A single injection of ibuprofen before surgery improved hippocampus-associated short-term memory after surgery and increased neurogenesis. However, this favorable outcome seemed not attributable to inhibition of (neuro)inflammation. Potential contributions of intestinal and blood-brain barrier integrity need further investigation. Although less pronounced compared to young rats, effects in aged rats indicate that even elderly individuals could benefit from ibuprofen treatment.

2016 ◽  
Vol 311 ◽  
pp. 15-23 ◽  
Author(s):  
Weronika Duda ◽  
Malgorzata Wesierska ◽  
Pawel Ostaszewski ◽  
Karel Vales ◽  
Tereza Nekovarova ◽  
...  

2012 ◽  
Vol 117 (5) ◽  
pp. 1091-1101 ◽  
Author(s):  
Jennifer K. Callaway ◽  
Nigel C. Jones ◽  
Alistair G. Royse ◽  
Colin F. Royse

Background Sevoflurane has been found to increase apoptosis and pathologic markers associated with Alzheimer disease, provoking concern over their potential contribution to postoperative cognitive dysfunction. Methods The effects of anesthesia with 1 minimum alveolar concentration of sevoflurane for 4 h or sham exposure on cognition were investigated in young adult and aged (20-24 months) rats at 1, 4, and 12 weeks postexposure. Spatial reference memory acquisition and retention were tested in the Morris water maze task. Latency to locate the hidden platform and swim speed were determined and compared between treatments. Results Sevoflurane anesthesia significantly reduced latency to find the hidden platform in both young adult (n = 10 per treatment, P < 0.0001) and aged rats (n = 7 per treatment, P < 0.0001) when tested 1 week after exposure. In young rats only, this improved acquisition learning was maintained at 4 (P = 0.003) but not at 12 weeks postexposure (P = 0.061). There were no differences in swim speed or in open field exploration between groups (no confounding effects of stress or locomotion). Retention memory measured using probe trials was not affected by exposure to sevoflurane in young adult or aged rats. Conclusion Sevoflurane anesthesia did not impair acquisition learning and retention memory in young adult or aged rats.


2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Pei-pei Feng ◽  
Pu Deng ◽  
Li-hua Liu ◽  
Qi Ai ◽  
Jie Yin ◽  
...  

Neuroinflammation has been suggested to be involved in the pathogenesis of postoperative cognitive dysfunction (POCD). Electroacupuncture (EA) is an irreplaceable method in traditional Chinese medicine that is used for treating neurodegenerative diseases in clinical and experimental studies. The aim of this study was to examine whether EA improves cognitive dysfunction caused by surgery and to investigate the pathological mechanism of TLR2 and TLR4 in the hippocampus of aged rats. A rat model of POCD was established and treated with EA or minocycline. Both EA- and minocycline-treated rats performed significantly better than untreated operated rats in spatial memory tasks of the Morris water maze (MWM) test, spending comparatively greater amounts of time in the target zone during the probe test. Additionally, decreased levels of proinflammatory cytokines (IL-1β, IL-6, TNF-α, and HMGB1) and decreased TLR2 and TLR4 protein expression in the hippocampus of EA- and minocycline-treated rats were detected. Our data suggested that EA treatment alleviated the cognition performance deficit and neuroinflammation in aged rats following surgery, which may be mediated by inhibiting the expression of hippocampal neuroinflammatory cytokines through the microglia/TLR2/4 pathway.


Author(s):  
Е.И. Захарова ◽  
З.И. Сторожева ◽  
А.Т. Прошин ◽  
М.Ю. Монаков ◽  
А.М. Дудченко

С целью изучения механизмов взаимодействия разных форм памяти исследовали зависимость формирования долговременной памяти от краткосрочной. Методы. Крыс обучали на пространственной обстановочной модели в водном лабиринте Морриса. Сравнивали результаты тестирования (время достижения скрытой платформы) первого дня обучения (краткосрочная память) и последующих трех, первые попытки в которых отражают этапы формирования долговременной памяти. Для сравнения использовали статистический метод разделения животных по способностям к обучению на квартили. Результаты. Крысы с выраженными способностями на всех этапах обучения составили лишь небольшую часть обучавшихся особей, в то время как большинство животных проявили разные способности к формированию краткосрочной памяти и консолидации долговременной. Были выявлены крысы, у которых 1) наряду со слабыми способностями на одном или на обоих этапах обучения в первый день тренировки проявились выраженные способности к консолидации долговременной памяти в последующие дни и, наоборот, 2) проявились выраженные способности к формированию краткосрочной памяти, а консолидация памяти оказалась нарушенной. Выводы. Полученные данные наглядно свидетельствуют о независимости механизмов краткосрочной и долговременной памяти. Aim. The dependence of long-term memory formation on short-term memory was studied to evaluate mechanisms for interaction of different memory forms. Methods. Rats were trained in the Morris water maze using the spatial contextual model of learning. We compared results of the test (time to reaching the hidden platform) on the first training day (short-term memory) and the first attempts on the next three days, which reflected stages in the consolidation of long-term memory. The comparison was performed using a statistical method of splitting animals into quartiles based on their learning ability. Results. The rats showing a good learning ability at all stages of training constituted only a small part of the trained animals while most animals showed different abilities to formation of short-term memory and consolidation of long-term memory. The rats were identified, which 1) although showed weak abilities at one or both stages of the first-day training showed good abilities to consolidate the long-term memory on the next days and, on the contrary, 2) showed good abilities to form the short-term memory while the memory consolidation was impaired. Conclusions. The study results clearly indicated a lack of dependence between mechanisms of short-term and long-term memory.


2021 ◽  
Vol 80 (3) ◽  
pp. 1185-1196
Author(s):  
Silvia Chapman ◽  
Preeti Sunderaraman ◽  
Jillian L. Joyce ◽  
Martina Azar ◽  
Leigh E. Colvin ◽  
...  

Background: The utility of subjective cognitive decline (SCD) as an indicator of preclinical AD is overshadowed by its inconsistent association with objective cognition. Objective: This study examines if manipulations of SCD measurement affect its association with early cognitive dysfunction characteristic of preclinical AD. Methods: Cognitively healthy older adults (n = 110) completed SCD questionnaires that elicited complaints in general, compared to 5 years ago (retrospective SCD) and compared to their peers (age-anchored SCD) in binary and Likert scales. Outcome cognitive tasks included an associative memory task (Face-Name Test), a visual short-term memory binding task (STMB test), and a clinical neuropsychological list learning test (Selective Reminder Test). Results: SCD complaints, when compared to age-matched peers (age-anchored SCD) were endorsed less frequently than complaints compared to 5 years ago (retrospective SCD) (p < 0.01). In demographically adjusted regressions, age-anchored ordinal-rated SCD was associated with short term memory binding (β= –0.22, p = 0.040, CI = –0.45, –0.01), associative memory (β= –0.26, p = 0.018, CI = –0.45, –0.06), and list learning (β= –0.31, p = 0.002, CI = –0.51, –0.12). Retrospective and general ordinal-rated SCD was associated with associative memory (β= –0.25, p = 0.012, CI = –0.44, –0.06; β= –0.29, p = 0.003, CI = –0.47, –0.10) and list learning only (β= –0.25, p = 0.014, CI = –0.45, –0.05; β= –0.28, p = 0.004, CI = –0.48, –0.09). Conclusion: Ordinal age-anchored SCD appears better suited than other SCD measurements to detect early cognitive dysfunction characteristic of preclinical AD.


2019 ◽  
Vol 373 ◽  
pp. 112107 ◽  
Author(s):  
Youbo Zuo ◽  
Xingping Hu ◽  
Qiuyan Yang ◽  
Lei Zhao ◽  
Xueli Chen ◽  
...  

1996 ◽  
Vol 5 (2) ◽  
pp. 205-223 ◽  
Author(s):  
Mark D. Lindner ◽  
Cristin E. Kearns ◽  
Shelley R. Winn ◽  
Beata Frydel ◽  
Dwaine F. Emerich

Exogenous NGF administered into the central nervous system (CNS) has been reported to improve cognitive function in aged rats. However, concerns have been expressed about the risks involved with supplying NGF to the CNS. In this study, baby hamster kidney cells (BHK) genetically modified to secrete human NGF (hNGF) were encapsulated in semipermeable membranes and implanted intraventricularly. ChAT/LNGFR-positive basal forebrain neurons were shown to atrophy and degenerate with age, especially in cognitively impaired rats. The encapsulated BHK-NGF cells produced less than 10% of doses previously reported to be effective, but this was sufficient to increase the size of ChAT/LNGFR-positive basal forebrain neurons in the aged and learning-impaired rats to the size of the neurons in young healthy rats. The hNGF from these encapsulated cells also improved performance in a repeated-acquisition version of the Morris water maze spatial learning task in learning-impaired 20.6- and 26.7- mo-old rats. Furthermore, there was no evidence that these doses of hNGF impaired Morris water maze performance in the youngest 3.3-5.4 mo rats, and analyses of mortality rates, body weights, somatosensory thresholds, potential hyperalgesia, and activity levels, suggested that these levels of exogenous hNGF are not toxic or harmful to aged rats. These results suggest that CNS-implanted semipermeable membranes, containing genetically modified xenogeneic cells continuously producing these levels of hNGF, attenuate age-related cognitive deficits in nonimmunosuppressed aged rats, and that both the surgical implantation procedure and long-term exposure to low doses of hNGF appear safe in aged rats.


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