Postoperative Cognitive Dysfunction: Preclinical Highlights and Perspectives on Preventive Strategies

One of the common complications associated with anaesthesia and surgery in geriatric patients is the postoperative cognitive dysfunction (POCD). This cognitive impairment affects the long-term prognosis and has been shown to be associated with long-term disability, higher health care costs, and even increased mortality. On the other hand, clinical research on POCD is in its infancy, the condition has not been clarified, and since no strategy for management is currently available, it is imperative to develop specific methods for prevention and management. Although its pathogenesis involves various factors, accumulating evidence suggests that surgery elicits an inflammatory response in the hippocampus, a brain area closely related to cognitive function, playing a key role in the development of POCD. Several studies suggest that age-related phenotypic change of microglia is associated with pathogenic neuroinflammation, and more importantly it may be modifiable. In this chapter, we discuss the current overview and preclinical highlights regarding POCD. We further discuss some perspectives on preventive strategies for POCD, based on the findings of our preclinical research and the available literature

Role of neurosteroid allopregnanolone on age-related differences in exercise-induced hypoalgesia in rats

The beneficial effects of physical activity for pain are denominated exercise-induced hypoalgesia (EIH). Here, we examined the age-related change and potential role of the neurosteroid allopregnanolone (ALLO) on EIH in rats. Adult and aged rats were randomly divided into one of three groups; non-exercise control, Low-exercise, and High-exercise. The animals in the Low- and High-exercise groups were subjected to a 10-minute treadmill workout at 40% and 80% maximum oxygen intake intensity, respectively. In the Low-exercise groups, a significant EIH response was observed in aged but not in adult rats. The pre-treatment with ALLO synthesis inhibitor finasteride, but not opioid-receptor antagonist naloxone, inhibited the Low-exercise induced EIH response in aged rats. Furthermore, the Low-exercise increased brain ALLO levels in aged animals compared with controls, which was correlated with the mechanical pain sensitivity. On the other hand, High-exercise could induce EIH response in both adult and aged animals, but it was more effective in adult rats. The pre-treatment with naloxone, but not finasteride, reduced the EIH observed after High-exercise in both adult and aged rats. Our findings demonstrated that effective EIH can be achieved even by mild-intensity exercise in aged animals via an increase of the brain ALLO levels

Resveratrol-loaded nanoemulsion prevents cognitive decline after abdominal surgery in aged rats

The maladaptive response of aged microglia to surgery and consequent neuroinflammation plays a key pathogenic role in postoperative cognitive dysfunction (POCD). Here, we assessed the preventive effect of resveratrol (RESV) for POCD in aged rats. The emulsified form of RESV (e-RESV) was selected to improve its oral and brain bioavailability. Animals were assigned to one of four groups: e-RESV (80 mg/kg) versus vehicle treatment by abdominal surgery versus isoflurane anesthesia alone (n = 8 in each group). The dose-dependent effects of e-RESV were also assessed in dose range of 0e60 mg/kg. Either vehicle or e-RESV was administered intragastrically 24 h before surgery. Seven days after procedure, cognitive function was evaluated using a novel object recognition test, followed by measurement of hippocampal pro-inflammatory cytokine levels. Our results showed that pre-treatment with e-RESV attenuated the surgery-induced cognitive impairment and related hippocampal neuroinflammation at 40 mg/kg or higher doses. Additionally, the ex-vivo experiments revealed that the preemptive e-RESV regimen reduced the hippocampal microglial immune reactivity to lipopolysaccharide. Furthermore, e-RESV induced neuroprotective benefits were inhibited by the concomitant administration of sirtinol, a specific SIRT1 inhibitor. Our findings imply the preventive potential of e-RESV for POCD via the SIRT1 signaling pathway

Restricted Outbreak of American Tegumentary Leishmaniasis with high microfocal transmission

Cutaneous leishmaniasis is endemic in Salta, the northwestern province of Argentina. We describe an outbreak involving five recreational hunters whose exposure was limited to several hours in a residual patch of primary forest. All patients presented with typical cutaneous lesions after a mean incubation period of 59 days (range 15–78), and one developed simultaneous mucosal involvement. Polymerase chain reaction analysis of lesions confirmed Leishmania (V.) braziliensis as the etiologic agent in three cases. All patients were cured with anti-Leishmania treatment. Entomologic surveys in the transmission area revealed a predominance of Lutzomyia neivai. This outbreak report confirms a microfocal transmission pattern of tegumentary leishmaniasis in the Americas and based on a well-determined exposure, allows the determination of incubation times for leishmaniasis caused by Leishmania braziliensis.Fil: Krolewiecki, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; Argentina. Universidad Nacional de Salta. Sede Regional Oran. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Gil, José Fernando. Universidad Nacional de Salta. Sede Regional Oran. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Quipildor, Marcelo. Universidad Nacional de Salta. Sede Regional Oran. Instituto de Investigacion de Enfermedades Tropicales; Argentina. Hospital San Vicente de Paul; ArgentinaFil: Cajal, Silvana P.. Universidad Nacional de Salta. Sede Regional Oran. Instituto de Investigacion de Enfermedades Tropicales; ArgentinaFil: Pravia, Carlos Alberto. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Juarez, Marisa. Universidad Nacional de Salta. Sede Regional Oran. Instituto de Investigacion de Enfermedades Tropicales; ArgentinaFil: Villalpando, Carlos. Universidad Nacional de Salta. Sede Regional Oran. Instituto de Investigacion de Enfermedades Tropicales; ArgentinaFil: Locatelli, Fabricio M.. Universidad Nacional de Salta. Sede Regional Oran. Instituto de Investigacion de Enfermedades Tropicales; ArgentinaFil: Chanampa, Mariana del Milagro. Universidad Nacional de Salta. Sede Regional Oran. Instituto de Investigacion de Enfermedades Tropicales; Argentina. Universidad Nacional de Salta. Facultad de Ciencias Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Castillo, Gabriela. Universidad Nacional de Salta. Facultad de Ciencias Naturales; ArgentinaFil: Oreste, Maria Fernanda. Universidad Nacional de Salta. Facultad de Ciencias Naturales; ArgentinaFil: Hoyos, Carlos Lorenzo. Universidad Nacional de Salta. Sede Regional Oran. Instituto de Investigacion de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Negri, Vanesa. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Nasser, Julio Rubén. Universidad Nacional de Salta. Sede Regional Oran. Instituto de Investigacion de Enfermedades Tropicales; Argentin

Resveratrol-loaded nanoemulsion prevents cognitive decline after abdominal surgery in aged rats

The maladaptive response of aged microglia to surgery and consequent neuroinflammation plays a key pathogenic role in postoperative cognitive dysfunction (POCD). Here, we assessed the preventive effect of resveratrol (RESV) for POCD in aged rats. The emulsified form of RESV (e-RESV) was selected to improve its oral and brain bioavailability. Animals were assigned to one of four groups: e-RESV (80 mg/kg) versus vehicle treatment by abdominal surgery versus isoflurane anesthesia alone (n = 8 in each group). The dose-dependent effects of e-RESV were also assessed in dose range of 0–60 mg/kg. Either vehicle or e-RESV was administered intragastrically 24 h before surgery. Seven days after procedure, cognitive function was evaluated using a novel object recognition test, followed by measurement of hippocampal pro-inflammatory cytokine levels. Our results showed that pre-treatment with e-RESV attenuated the surgery-induced cognitive impairment and related hippocampal neuroinflammation at 40 mg/kg or higher doses. Additionally, the ex-vivo experiments revealed that the preemptive e-RESV regimen reduced the hippocampal microglial immune reactivity to lipopolysaccharide. Furthermore, e-RESV induced neuroprotective benefits were inhibited by the concomitant administration of sirtinol, a specific SIRT1 inhibitor. Our findings imply the preventive potential of e-RESV for POCD via the SIRT1 signaling pathway. Keywords: Resveratrol, Neuroinflammation, Postoperative cognitive dysfunction, Microgli

Role of neurosteroid allopregnanolone on age-related differences in exercise-induced hypoalgesia in rats

The beneficial effects of physical activity for pain are denominated exercise-induced hypoalgesia (EIH). Here, we examined the age-related change and potential role of the neurosteroid allopregnanolone (ALLO) on EIH in rats. Adult and aged rats were randomly divided into one of three groups; non-exercise control, Low-exercise, and High-exercise. The animals in the Low- and High-exercise groups were subjected to a 10-minute treadmill workout at 40% and 80% maximum oxygen intake intensity, respectively. In the Low-exercise groups, a significant EIH response was observed in aged but not in adult rats. The pre-treatment with ALLO synthesis inhibitor finasteride, but not opioid-receptor antagonist naloxone, inhibited the Low-exercise induced EIH response in aged rats. Furthermore, the Low-exercise increased brain ALLO levels in aged animals compared with controls, which was correlated with the mechanical pain sensitivity. On the other hand, High-exercise could induce EIH response in both adult and aged animals, but it was more effective in adult rats. The pre-treatment with naloxone, but not finasteride, reduced the EIH observed after High-exercise in both adult and aged rats. Our findings demonstrated that effective EIH can be achieved even by mild-intensity exercise in aged animals via an increase of the brain ALLO levels. Keywords: Neurosteroid, Allopregnanolone, Aging, Exercise, Acute pai

The isolation and molecular characterization of Leishmania spp. from patients with American tegumentary leishmaniasis in northwest Argentina

American tegumentary leishmaniasis (ATL) is a group of zoonotic diseases caused by kinetoplastid flagellates of the genus Leishmania. A total of 66 patients diagnosed as positive ATL cases from northwest Argentina were included in this study. Leishmania stocks were isolated in vitro and analyzed over promastigote cultures sown on FTA through nested PCR and sequence of cytochrome b (cyt b). The molecular analysis resulted in the incrimination of L. (Viannia) braziliensis as the predominant species in the studied area, identifying two genotypes of L. (V.) braziliensis, 24 cases of Ab-1 cyt b and 41 cases of Ab-2 cyt b. One L. (V.) guyanensis strain was obtained from a traveler from the Brazilian Amazon. The prevalence of different genotypes was in agreement with previous studies, suggesting the necessity for new systems to study the genetic diversity in more detail. Most of the cases typified in this study were registered in the area of Zenta Valley (Orán, Hipólito Yrigoyen, and Pichanal cities), pointing a link between genotype and geographical origin of the sample. Sex and age distribution of the patients indicate that the transmission was predominantly associated with rural areas or rural activities, although the results might not exclude the possibility of peri-urban transmission. This work represents, so far, the largest isolation and molecular characterization of ATL cases in ArgentinaFil: Locatelli, Fabricio M.. Kochi University. Kochi Medical School. Dept.of Parasitology; Japón. Universidad Nacional de Salta. Sede Regional Oran. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Cajal, S. Pamela. Universidad Nacional de Salta. Instituto de Investigaciones en Enfermedades Tropicales; ArgentinaFil: Barroso, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; Argentina. Universidad Nacional de Salta. Sede Regional Oran. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Lauthier, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; ArgentinaFil: Mora, Maria Celia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; ArgentinaFil: Juarez, Marisa. Universidad Nacional de Salta. Instituto de Investigaciones en Enfermedades Tropicales; ArgentinaFil: Kato, Hirotomo. Hokkaido University; JapónFil: Nasser, Julio R.. Universidad Nacional de Salta. Instituto de Investigaciones en Enfermedades Tropicales; ArgentinaFil: Hashiguchi, Yoshihisa. Universidad Central del Ecuador y Proyecto Prometeo; Ecuador. Kochi University. Kochi Medical School. Dept.of Parasitology; JapónFil: Korenaga, Masataka. Kochi University. Kochi Medical School. Dept.of Parasitology; JapónFil: Marco, Jorge Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; Argentina. Universidad Nacional de Salta. Sede Regional Oran. Instituto de Investigación de Enfermedades Tropicales; Argentin