Synapses develop concurrently and at identical rates in different layers of the visual, somatosensory, motor, and prefrontal areas of the primate cerebral cortex. This isochronic course of synaptogenesis in anatomically and functionally diverse regions indicates that the entire cerebral cortex develops as a whole and that the establishment of cell-to-cell communication in this structure may be orchestrated by a single genetic or humoral signal. This is in contrast to the traditional view of hierarchical development of the cortical regions and provides new insight into the maturation of cortical functions.

Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and

Inhaled anesthetics enhance oligomerization and cytotoxicity of Alzheimer disease-associated peptides. In addition to the possibility of a general mechanism for anesthetic neurotoxicity, these results call for further evaluation of the interaction between neurodegenerative disorders, dementia, and inhalational anesthesia.

Inhaled anesthetics have been shown to increase the aggregation of amyloid beta in vitro through the stabilization of intermediate toxic oligomers, which are thought to contribute to neurocognitive dysfunction in Alzheimer's disease. Inhaled anesthetics may escalate cognitive dysfunction through enhancement of these intermediate oligomer concentrations. We intermittently exposed 12-month-old Tg2576 transgenic mice and nontransgenic littermates to isoflurane and halothane for 5 days. Cognitive function was measured before and after anesthetic exposures using the Morris Water Maze; amyloid beta plaque burden and caspase-3 mediated apoptosis were quantified by immunohistochemistry. At 12 months of age, anesthetic exposure did not further enhance cognitive decline in the transgenic mice. Immunohistochemistry, however, revealed that the halothane-exposed Tg2576 mice had more amyloidopathy than the isoflurane treated mice or the nonexposed transgenic mice. Isoflurane exposure impaired cognitive function in the nontransgenic mice, implying an alternative pathway for neurodegeneration. These findings indicate that inhaled anesthetics influence cognition and amyloidogenesis, but that the mechanistic relationship remains unclear.

Background The prevalence of post-operative cognitive disturbance, coupled with growing in vitro, cell and animal evidence suggesting anesthetic effects on neurodegeneration, calls for further study of the interaction between surgical care and Alzheimer neuropathology. Here, we study human cerebral spinal fluid (CSF) biomarkers perioperatively. Methods Eleven patients undergoing idiopathic nasal CSF leak correction joined this Institutional Review Board approved study. Lumbar subarachnoid catheters were placed prior to the procedure. Anesthesia was total intravenous anesthesia (propofol/remifentanil) or inhalational (sevoflurane), depending on provider choice. CSF samples were taken after catheter placement (base), at procedure end (0h), and then at 6, 24 and 48h. CSF was analyzed using xMAP Luminex immunoassay (Luminex, Austin, TX). Results Patients: 53±6 yrs old; 8 women; 4 received intravenous anesthesia, 6 sevoflurane, 1 mixed. Procedures lasted 6.4 ± 2h. Mean CSF amyloid-β1-42 remained unchanged, but total-tau and phosphorylated-tau181P increased progressively until at least 48h. Total-tau, phosphorylated-tau or amyloid-β1-42 levels were not different between anesthetic groups. CSF interleukin-10, S100B and tumor necrosis factor alpha were increased similarly in both anesthetic groups at 24h, but interleukin-6 was increased more in the inhalational group. Conclusion These data indicate a robust neuroinflammatory response, including not only the usual markers (interleukin-6, tumor necrosis factor α, interleukin-10), but also S100B and tau, markers of injury. The total-tau/amyloid-β1-42 ratio increased in a pattern consistent with Alzheimer disease, largely due to an increase in total-tau rather than a decline in amyloid-β1-42. The differences in CSF interleukin-6 levels, suggest that anesthetic management may make a difference in neuroinflammatory response.