Biomedical subjects

Verna L Baughman

Publications and source records attributed to Verna L Baughman.

4 recordsLinked to original sources

PubMed2002

Loss of benefit from estrogen replacement therapy in diabetic ovariectomized female rats subjected to transient forebrain ischemia.

In nondiabetic animals, estrogen has been shown to provide significant neuroprotection in focal and transient forebrain ischemia models. However, that neuroprotection may be diminished or lost in the diabetic. In this study, we compared the level of brain damage in intact, ovariectomized (OVX) and 17beta-estradiol (E(2))-treated OVX female rats rendered diabetic and chronically ( approximately 4 weeks) hyperglycemic via streptozotocin (STZ). Rats were subjected to 20 min of unilateral transient forebrain ischemia (reduction in cortical CBF to 20% of baseline). Neurologic function was analyzed daily and brain histopathology (in H&E-stained sections) was evaluated at 72 h of reperfusion. Supplemental histopathologic information was obtained from additional TUNEL-stained sections. When comparing neurologic outcome scores in the three groups, E(2)-treated OVX females displayed the highest degree of dysfunction and intact females the least (OVX rats not treated with E(2) were intermediate), with the difference between the intact and E(2)-treated groups being statistically significant. That same order was often observed with the regional histopathologic analyses of H&E-stained tissue. A significantly higher magnitude of neuronal loss in both OVX groups, when compared to intact females, was observed in the CA4 sector of the hippocampus and in the cortex. In addition, cell loss in the dorsal thalamus of the E(2)-treated group was significantly greater than in the intact females. Those results were generally corroborated by TUNEL-analysis, with 67% of the E(2)-treated, 33% of the control OVX, and only 17% of the intact females displaying TUNEL-positive cells in multiple regions. In conclusion, the present findings strongly suggest that the neuroprotective benefits of estrogen replacement therapy may be lost in the diabetic female rat.

Animals↗

PubMed2002

Brain protection during neurosurgery.

The initial concept of brain protection during neurosurgery is based on research done in the 1970s-1980 which established the concept that by decreasing cerebral metabolic rate the brain could survive longer periods of ischemia. The first section of this chapter reviews some of this initial research that promoted the use of barbiturates for cerebral protection. The second section reviews current anesthetic drugs and their potential for cerebral protection in addition to the benefits of blood pressure, temperature and glucose control. The final section discusses the "new mechanisms of cerebral protection" and the role old and new drugs may play in the future for brain protection during neurosurgery.

Anesthetics↗

PubMed2002

GABA alpha6 receptors mediate midazolam-induced anxiolysis.

STUDY OBJECTIVE: To compare the ability of midazolam to produce sedation and anxiolysis and attenuate memory in 100 patients aged 20 to 70 years. The effect of a point mutation (Pro385Ser) for the gamma amino-butyric acid (GABA) alpha6 receptor on the sedative, anxiolytic, and memory effects of midazolam was determined. SETTING: University hospital. DESIGN: Prospective, randomized, double-blind study. PATIENTS: 100 ASA physical status I and II patients scheduled for surgery. INTERVENTIONS: Two midazolam dose groups, 20 microg/kg and 40 microg/kg, with 40 patients per group and 20 control patients receiving saline as a sham control. Treatments were randomly assigned. Blood was collected at the beginning of each study. MEASUREMENTS: Patient sedation and anxiolysis were measured using a visual analog scale and explicit and implicit memory of a word task determined before and six minutes after midazolam or saline. A 365-base pair fragment of the GABA alpha6 receptor gene was amplified by polymerase chain reaction (PCR) from patient blood DNA and digested with the restrictase Fok I. Restriction fragments were visualized by ethidium bromide staining after electrophoresis to evaluate the GABA alpha6 receptor subunit mutation. MAIN RESULTS: Midazolam produced dose-related sedation and anxiolysis. Explicit (recall) memory was attenuated with high-dose midazolam but implicit (recognition) memory remained intact. The GABA alpha6 receptor mutation did not affect baseline sedation, anxiety, or memory but significantly attenuated the anxiolytic effect of low-dose midazolam. Sedation and explicit memory were not affected by the mutation. CONCLUSIONS: A Pro385Ser mutation of the GABA alpha6 receptor subunit decreased the anxiolytic effect of low-dose midazolam.

Adult↗

PubMed2002

Combined endothelial nitric oxide synthase upregulation and caveolin-1 downregulation decrease leukocyte adhesion in pial venules of ovariectomized female rats.

BACKGROUND AND PURPOSE: We recently found that chronic estrogen depletion enhances leukocyte adhesion in pial venules in the female rat, while estrogen repletion decreases it. Estrogen-associated repression of inflammation may be due to upregulation of the endothelial isoform of nitric oxide synthase (eNOS) and concomitant downregulation of the endogenous inhibitor of eNOS, caveolin-1 (CAV-1). In this study we examined the effects of estrogen-independent eNOS upregulation (via simvastatin) and/or CAV-1 downregulation (antisense) on pial venular leukocyte adhesion in ovariectomized (OVX) rats. METHODS: Intact and OVX rats were prepared with closed cranial windows. Adherent rhodamine 6G-labeled leukocytes were viewed by intravital microscopy. To demonstrate the importance of pial venular eNOS in the resistance to leukocyte adhesion, intact female rats were treated with a nonselective (N(G)-nitro-L-arginine) or a neuronal NOS-selective (7-nitroindazole) inhibitor. In OVX females, leukocyte adhesion was compared in the following groups: (1) untreated; (2) treated with simvastatin; (3) treated with simvastatin plus CAV-1 antisense; (4) treated with simvastatin plus CAV-1 missense; (5) treated with CAV-1 antisense; and (6) treated with CAV-1 missense. RESULTS: In intact females, pial venular leukocyte adhesion was increased when total NOS activity, but not neuronal NOS activity alone, was blocked. In OVX rats, basal leukocyte adhesion, measured as the percentage of venular area occupied by adherent leukocytes, was attenuated (by approximately equal 60%) only in the presence of combined simvastatin plus CAV-1 antisense treatment. CONCLUSIONS: Present findings demonstrate that eNOS-derived NO plays an important role in limiting cerebral venular leukocyte adhesion in female rats. These data also suggest that simvastatin-induced upregulation of eNOS expression in OVX rats will not restore eNOS function, as measured by decreased leukocyte adhesion, unless CAV-1 levels are reduced as well.

Animals↗