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Gregory Crosby

Publications and source records attributed to Gregory Crosby.

12 recordsLinked to original sources
PubMed2006

Altered hippocampal gene expression 2 days after general anesthesia in rats.

We profiled changes in gene expression in the hippocampus 2 days after a 4 h general anesthetic with isoflurane and nitrous oxide. Eighteen month old Fisher 344 rats were anesthetized for 4 h with 1.2% isoflurane and 70% nitrous oxide (N=9) whereas control rats breathed 30% oxygen for 4 h (N=9). Rats were sacrificed 48 h later and RNA extracted from the hippocampus for gene expression profiling. Three gene arrays were used per group, with samples prepared by pooling RNA from three rats. Differentially expressed genes were analyzed based on a weighted error statistical model. Microarray results for 6 differentially expressed genes were verified with reverse transcriptase polymerase chain reaction. Compared to unanesthetized controls, 297 genes were differentially expressed 2 days following anesthesia (P<0.05). Of these, 113 are named genes; 64% were up-regulated and 36% were down-regulated. The majority of differentially expressed genes are implicated in cell stress and replication, signal transduction, transcription, protein biosynthesis, cell structure, and metabolism. The correlation between fold changes on array and reverse transcriptase polymerase chain reaction was good (R2=0.85) for the 6 genes examined with both methods. These results demonstrate that in rats general anesthesia is associated with persistent changes in hippocampal gene expression, suggesting that recovery of the brain from anesthesia is considerably slower than generally recognized.

Anesthetics, Inhalation↗
PubMed2006

The common inhalation anesthetic isoflurane induces apoptosis and increases amyloid beta protein levels.

BACKGROUND: The common inhalation anesthetic isoflurane has previously been reported to enhance the aggregation and cytotoxicity of the Alzheimer disease-associated amyloid beta protein (Abeta), the principal peptide component of cerebral beta-amyloid deposits. METHODS: H4 human neuroglioma cells stably transfected to express human full-length wild-type amyloid precursor protein (APP) were exposed to 2% isoflurane for 6 h. The cells and conditioned media were harvested at the end of the treatment. Caspase-3 activation, processing of APP, cell viability, and Abeta levels were measured with quantitative Western blotting, cell viability kit, and enzyme-linked immunosorbent assay sandwich. The control condition consisted of 5% CO2 plus 21% O2 and balanced nitrogen, which did not affect caspase-3 activation, cell viability, APP processing, or Abeta generation. RESULTS: Two percent isoflurane caused apoptosis, altered processing of APP, and increased production of Abeta in H4 human neuroglioma cell lines. Isoflurane-induced apoptosis was independent of changes in Abeta and APP holoprotein levels. However, isoflurane-induced apoptosis was potentiated by increased levels of APP C-terminal fragments. CONCLUSION: A clinically relevant concentration of isoflurane induces apoptosis, alters APP processing, and increases Abeta production in a human neuroglioma cell line. Because altered processing of APP leading to accumulation of Abeta is a key event in the pathogenesis of Alzheimer disease, these findings may have implications for use of this anesthetic agent in individuals with excessive levels of cerebral Abeta and elderly patients at increased risk for postoperative cognitive dysfunction.

Amyloid beta-Peptides↗
PubMed2006

General anesthesia does not reduce life expectancy in aged rats.

A recent clinical study demonstrated that deep anesthesia, as measured by Bispectral index monitoring, was associated with increased 1-yr mortality among middle-aged and elderly surgical patients. We have previously demonstrated impaired cognitive performance in aged rats for weeks after general anesthesia with 1.2% isoflurane-70% nitrous oxide-30% oxygen. However, the effects of 2 h of anesthesia with 1.2% isoflurane-70% nitrous oxide-30% oxygen on rodent life expectancy are unknown and may have confounded our results. Accordingly, we designed this study to determine if general anesthesia alters life expectancy in aged rats. Sixteen 22-mo-old Fischer 344 rats were randomized to anesthesia for 2 h with 1.2% isoflurane-70% nitrous oxide-30% oxygen or a control group that received 30% oxygen (n = 8 per group). Rats recovered in an enriched oxygen environment and then were placed in their home cage under routine conditions. The number of days between anesthesia administration and death were recorded and Kaplan-Meier survival curves generated and compared statistically using the log-rank test and bootstrap method. There was no difference in long-term survival between the control and anesthesia groups. Hence, general anesthesia with 1.2% isoflurane-70% nitrous oxide-30% oxygen does not reduce life expectancy in aged Fischer 344 rats.

Aging↗
PubMed2005

Spatial memory performance 2 weeks after general anesthesia in adult rats.

We have previously demonstrated that general anesthesia with 1.2% isoflurane-70% nitrous oxide impairs acquisition of a radial arm maze task in both young and aged rats when testing begins 2 days after anesthesia and in aged rats when testing begins 2 wk later. We designed this study to examine whether postanesthesia learning impairment is persistent in young rats. Six-month-old rats were randomized to anesthesia for 2 h with 1.2% isoflurane-70% nitrous oxide, 1.8% isoflurane, or a control group that received 30% oxygen (n = 10 per group). Rats recovered for 2 wk and were then tested daily on a radial arm maze for 14 days. There were no differences between the controls and anesthesia groups in number of correct choices to first error or time to complete the maze. There was no main effect of group in terms of total number of errors (P > 0.05) but the group by day interaction was significant (P < 0.05), reflecting improved performance in the 1.2% isoflurane-70% nitrous oxide group relative to controls during the later days of testing (P < 0.005). Hence, in adult rats, previous general anesthesia is not associated with impaired learning 2 wk later. In fact, previous 1.2% isoflurane-70% nitrous oxide improves maze performance 2 wk later.

Anesthesia, General↗
PubMed2004

Hemorrhagic stroke after spinal anesthesia and minor surgery.

This report describes a case of hemorrhagic stroke that presented as an expressive aphasia after routine hernia repair under spinal anesthesia in an otherwise generally healthy middle-aged outpatient. Possible roles of preexisting migrainous headaches and perioperative ephedrine are discussed, but, as in most cases of perioperative stroke, the possibilities are numerous and the cause of the stroke difficult to determine.

Anesthesia, Spinal↗
PubMed2004

NMDA-R1 antisense oligodeoxynucleotides modify formalin-induced nociception and spinal c-Fos expression in rat spinal cord.

Noxious peripheral stimuli (thermal, mechanical, or chemical) produce long-term adaptations in the sensitivity of central nociceptive neurons to subsequent noxious stimuli. The mechanisms responsible for this central sensitization are multifactorial, but the activation of spinal N-methyl-D-aspartate (NMDA) receptors plays a pivotal role. Using antisense oligodeoxynucleotides, we tested the role of the NR1 subunit of the NMDA receptor in the nociception and expression of the immediate early gene c-fos following formalin-induced pain. Rats received NMDA-R1 antisense, sense, or missense oligodeoxynucleotides intrathecally three times over a 48-h interval. The day after the last injection of the oligodeoxynucleotide, the formalin test was performed. Pain-related behavior was quantified by counting the incidence of flinching of the injected paw for 60 min, and the animals were perfused and the spinal cord removed for c-Fos immunohistochemistry 60 min later. Immunopositive cells were counted in the laminae I/II(0) and V of the lumbar enlargement. Treatment with NR1 antisense oligodeoxynucleotide resulted in a marked decrease in flinching. Similarly, the antisense oligodeoxynucleotide virtually abolished formalin-induced expression of c-Fos-like immunoreactivity (Fos-IR) in the spinal cord dorsal horn ipsilateral to injection. In contrast, the corresponding sense or missense oligodeoxynucleotides had no effect on either formalin-evoked behavior or c-Fos immunoreactivity. We conclude that an NR1 antisense oligodeoxynucleotide inhibits both nociceptive behavior and c-fos expression following formalin injection in rats, demonstrating that NR1 plays an important role in the development of noxious stimulation induced c-fos expression in this model.

Animals↗
PubMed2004

Long-term impairment of acquisition of a spatial memory task following isoflurane-nitrous oxide anesthesia in rats.

BACKGROUND: The authors demonstrated previously that isoflurane-nitrous oxide anesthesia attenuates performance improvement on an already-learned spatial memory task and that the effect persists for weeks. This experiment was designed to test the hypothesis that learning of new information is particularly susceptible to prolonged disruption after general anesthesia. METHODS: Six- (n = 5) and 20- (n = 5) month-old male Fischer 344 rats were anesthetized for 2 h with 1.2% isoflurane, 70% nitrous oxide, and 30% oxygen. Age-matched control rats received 30% oxygen and 70% nitrogen (n = 5 per group). Rats breathed spontaneously, and anesthetic and oxygen concentrations were measured. Spatial learning was assessed daily for 21 days on a 12-arm radial maze (RAM) beginning 48 h after anesthesia. In a post hoc experiment to examine locomotion, swim speed was assessed in a separate group of identically treated rats (n = 3 per group) for 4 days beginning 48 h after anesthesia. RESULTS: Aged rats were slower to complete the maze, made fewer correct choices before first error, and made more errors at baseline than young rats (P < 0.05). Anesthesia worsened maze performance in both age groups, as evidenced by increased time to complete the maze and a decreased number of correct choices before first error (P < 0.05), but there were no statistically significant differences in total number of errors. Interestingly, there were no age-by-anesthesia interactions. Aged rats swam slower than adult rats (P < 0.001), but there were no differences between the control and anesthesia groups. CONCLUSIONS: Isoflurane-nitrous oxide anesthesia is associated with a persistent deficit in RAM performance that is not explained by impaired locomotion. This impairment occurs in adult and aged rats, indicating that it is not an age-specific phenomenon. Thus, RAM performance is altered after general anesthesia for longer than predicted by the pharmacology of the drugs used, which, by inference, suggests a long-term deficit in learning/memory.

Aging↗
PubMed2004

Impaired acquisition of spatial memory 2 weeks after isoflurane and isoflurane-nitrous oxide anesthesia in aged rats.

Aged rats are impaired on a spatial memory task for at least 24-48 h after isoflurane-nitrous oxide anesthesia. In this study, we tested how long the impairment lasts and investigated the role of nitrous oxide. Eighteen-month-old rats were randomized to anesthesia for 2 h with 1.2% isoflurane with or without 70% nitrous oxide or a control group (30% oxygen). Two weeks later, rats were tested daily for 14 days on a 12-arm radial maze. The number of correct choices to first error, total errors, and time to complete the maze were recorded. Rats anesthetized with 1.2% isoflurane with 70% nitrous oxide made fewer correct choices before first error (P < or = 0.05). Trends toward similar results were noted for error rate and time to complete the maze, but these did not achieve statistical significance. Post hoc analysis comparing all anesthetized rats to controls demonstrated that anesthetized rats made fewer correct choices to first error (P < or = 0.05) and took longer to complete the maze (P <or = 0.05). There were no differences in total number of errors (P < or = 0.06). Thus, spatial memory is impaired for 2 wk after general anesthesia in aged rats independent of whether nitrous oxide is used.

Aging↗
PubMed2003

The memory effects of general anesthesia persist for weeks in young and aged rats.

UNLABELLED: Studies demonstrate lasting cognitive impairment in elderly persons after anesthesia and surgery. We tested the hypothesis that general anesthesia contributes to this cognitive impairment. Six- and 18-mo-old Fischer 344 rats were trained in a 12-arm radial arm maze and were then randomized to anesthesia for 2 h with 1.2% isoflurane/70% nitrous oxide/30% oxygen or a control treatment consisting of 30% oxygen. Rats recovered for 24 h and then were tested daily on the radial arm maze for 8 wk. Performance of young control rats was stable throughout the experiment. In contrast, aged control rats improved their performance as measured by time to complete the maze but not by error rate. After anesthesia, time to complete the maze did not change in young rats, but error rate decreased (P < 0.05 at 1 and 3 wk), indicating improved performance. In contrast, previously anesthetized aged rats failed to improve with repeated testing and took longer to complete the maze than aged control rats (P < 0.05 at 1 and 3 wk). These data demonstrate that general anesthesia with isoflurane and nitrous oxide improves the memory performance on an established spatial memory task in young rats, but in aged rats it attenuates the improvement in performance that otherwise occurs with repeated testing. Therefore, isoflurane and nitrous oxide anesthesia produces a sustained learning impairment in aged rats. IMPLICATIONS: This study demonstrates that general anesthesia with isoflurane and nitrous oxide improves spatial memory in young rats but impairs it in aged rats for at least 3 wk, indicating that it can influence memory for much longer than previously recognized and may adversely affect memory processes in the aged.

Aging↗
PubMed2002

Antisense oligonucleotides to N-methyl-D-aspartate receptor subunits attenuate formalin-induced nociception in the rat.

Noxious peripheral stimuli increase the sensitivity of central nociceptive neurons to subsequent noxious stimuli. This occurs in part through activation of spinal N-methyl-D-aspartate (NMDA) receptors. These receptors are heteromeric complexes of NMDA-R1 and NMDA-R2 A--D subunits. NMDA-R1 is necessary for the formation of functional NMDA receptors whereas the R2 subunits (A-D) modify the properties of the receptor. However, the role of the various receptor subtypes in nociception has not been established. In this study, we used intrathecally administered phosphodiester antisense oligonucleotides (ODEs) to examine the role of the NMDA-R1, NMDA-R2C and NMDA-R2D subunits in the mediation of formalin-induced nociception in the rat. The antisense ODEs against the NMDA-R1 and NMDAR-2C subunits reduced nociceptive behaviors whereas the corresponding sense ODEs had no effect. In contrast, nociception was unaffected by the antisense ODE to NMDAR-2D. Using an RNase protection assay, we also found that each antisense ODE selectively decreased the level of the corresponding mRNA in the lumbar spinal cord but that the sense ODEs had no such effect. Accordingly, these data provide evidence that the R1 and R2C subunits, but not R2D, of the NMDA receptor participate in the development of formalin-induced nociception.

Analgesics, Non-Narcotic↗