The use of anesthetics and sedatives has been suggested to be a contributor to Alzheimer's disease neuropathogenesis. We wanted to address the in vivo relevance of those substances in the Tg2576 Alzheimer's mouse model. Tg7526 mice were anesthesia-sedated for 90 min once a week for 4 weeks. Y maze, Congo Red, and amyloid beta (Aβ) immunochemistry were performed. We did not find any significant change in the navigation behavior of the exposed mice compared to the controls. Significantly less deposition of Aβ in the CA1 area of the hippocampus and frontal cortex of mice exposed to isoflurane, propofol, diazepam, ketamine, and pentobarbital was observed. In the dentate gyrus, Aβ deposition was significantly greater in the group treated with pentobarbital. Congo Red staining evidenced significantly fewer fibrils in the cortex of mice exposed to diazepam, ketamine, or pentobarbital. The adopted repetitive exposure did not cause a significant detriment in Tg7526 mouse.

Brief episodes of hypotension have been shown to cause acute brain damage in animal models. We used a rat hemorrhagic shock model to assess functional outcome and to measure the relative neuronal damage at 1, 4 and 14 days post-injury (3 min of hypotension). All rats underwent a neurological assessment including motor abilities, sensory system evaluation and retrograde memory at post-hypotensive insult. Brains were harvested and stained for Fluorojade C and Nissl. Stereology was used to analyze Fluorojade C and Nissl stained brain sections to quantitatively detect neuronal damage after the hypotensive insult. Statistical analysis was performed using Graphpad Prism 5 with the Bonferroni test at a 95% confidence interval after ANOVA. A Mixed Effect Model was used for the passive avoidance evaluation. Stereologically counted fluorojade positive cells in the hippocampus revealed significant differences in neuronal cell injury between control rats and rats that received 3 min of hypotension one day after insult. Quantification of Nissl positive neuronal cells showed a significant decrease in the number hippocampal cells at day 14. No changes in frontal cortical cells were evident at any time, no significative changes in neurological assessments as well. Our observations show that brief periods of hemorrhage-induced hypotension actually result in neuronal cell damage in Sprague–Dawley rats even if the extent of neuronal damage that was incurred was not significant enough to cause changes in motor or sensory behavior.

Caspase inhibitors are usually administered intracranially. There's very limited evidence showing that they can be used intraperitoneally, and still have a beneficial effect. We tested the hypothesis that, during focal cerebral ischemia, caspase inhibitors when used in combination with an anesthetic agent results in a significantly reduction in the neuronal damage. Male Sprague Dawley rats were randomly divided into six different groups: control, Isoflurane, Propofol, Isoflurane and Caspase-3 inhibitor intraperitoneally (IP), propofol and Caspase-3 inhibitor IP and only caspase-3 inhibitor, during post-ischemia. Neurological evaluation and histochemical analysis was assessed post-ischemia. The treatment proposed, resulted in a significant decrease in the cerebral infarction volume. Combination of treatments, and caspase-3 inhibitor alone significantly decreased the number of TUNEL and cleaved caspase-3 positive cells in the boundary area of cortical infarction. IP administration appears to reach cerebral targets similarly to intracerebral model. This combination reduces the neurological damage caused by focal cerebral ischemia.

This observation suggests that in this model of hypotension plus hypoxia there is mild cerebral damage that is reflected by memory changes. Exposure to isoflurane after the insult can prevent the onset of memory deficits.