Biomedical subjects

Stephen W Scheff

Publications and source records attributed to Stephen W Scheff.

23 records · Page 2Linked to original sources

PubMed2002

Traumatic brain injury regulates adrenocorticosteroid receptor mRNA levels in rat hippocampus.

Glucocorticoid activation of two types of adrenocorticosteroid receptors (ACRs), the mineralocorticoid receptor (MR) and glucocorticoid receptor (GR), influences the vulnerability of hippocampal neurons to insult. To examine the potential impact of ACR activation following traumatic brain injury (TBI), the current study assesses regulation of MR and GR expression and glucocorticoid levels following controlled cortical impact (CCI). Male Sprague-Dawley rats were pretreated for 48 h with vehicle, the MR antagonist spironolactone, or the GR antagonist mifepristone (RU486). On day three, subjects were sham-operated or injured by unilateral CCI. In situ hybridization analysis determined that pretreatment with either MR antagonist spironolactone or GR antagonist RU486 increased 24-h hippocampal GR mRNA levels in sham-operated animals only, suggesting that MR and GR regulation of GR mRNA is suppressed following TBI. Injury decreased GR mRNA levels in the ipsilateral dentate gyrus of all pretreatment groups and bilaterally increased MR mRNA levels in CA3 of antagonist-pretreated animals. One day post-injury, plasma corticosterone levels were comparable in sham and injured animals pretreated with vehicle. A separate group of animals that did not receive pretreatment injections prior to sham operation or injury were included for a 24-h time course analysis of plasma ACTH and corticosterone levels. Injury increased hypothalamic-pituitary-adrenal (HPA) activation for approximately 6 h following injury. These results indicate that hippocampal ACR mRNA levels and HPA activation are altered by TBI. Regulation of MR and GR expression following TBI may influence hippocampal neuron viability by modulating glucocorticoid signaling after injury.

Adrenocorticotropic Hormone↗

PubMed2002

Efficacy of methylprednisolone therapy for the injured rat spinal cord.

Currently the synthetic glucocorticosteroid methylprednisolone sodium succinate (MPSS) is the standard therapy after acute spinal cord injury (SCI) in humans based on reported neurological improvements. The mechanisms for its beneficial actions are not entirely clear, but experimental evidence suggests MPSS affords some degree of neuroprotection. As many studies with rat models of SCI have been unable to demonstrate improved behavioral outcome or tissue sparing after MPSS treatment, we chose to stereologically assess whether it alters lesion volume and tissue sparing over time, as well as long-term behavioral recovery. Adult rats subjected to contusion SCI with the NYU impactor were administered either MPSS or saline for 24 hr beginning 5 min post injury. Over time the lesion dimensions were extremely dynamic, such that by 6 weeks post injury the volumes were reduced to a third of those seen after the first week. MPSS marginally reduced lesion volumes across time vs. controls, but the amount of spared gray and white matter remained unaltered between the two groups. Behavioral results further showed that MPSS failed to improve recovery of hind-limb function. These findings add to the emerging scrutiny of MPSS as the standard therapy for acute SCI, as well as indicate the existence of a therapeutic window for tissue sparing restricted to the first several days after this type of SCI in rats. Equally important, our results caution the use of lesion volume dimensions or percent tissue sparing at the epicenter as indicators of therapeutic efficacy because neither reflects the actual amount of tissue sparing.

Animals↗

PubMed2002

A statistical method for analyzing rating scale data: the BBB locomotor score.

The Basso, Beattie and Bresnahan (BBB) locomotor rating scale is widely used to test behavioral consequences of spinal cord injury (SCI) to the rat. Sensitivity of this rating scale can differentiate hind limb locomotor skills over a wide range of injury severities. While the 21-point BBB scale is ordinal in nature, the present discussion recommends the use of parametric statistics to evaluate the locomotor results. Specifically, it defines appropriate statistical analysis of these data in order to facilitate interpretation of results between laboratories and to provide a common methodology for the correct interpretation of SCI behavioral data.

Analysis of Variance↗

PubMed2002

Time-dependent changes in rat brain cholinergic receptor expression after experimental brain injury.

Alterations in neurotransmitter receptor expression in the central nervous system may contribute to physiological and behavioral deficits that follow traumatic brain injury (TBI). Previous studies from our laboratory have demonstrated significant and widespread deficits in alpha7* nicotinic cholinergic receptor (alpha7* nAChr) expression 2 days following cortical contusion brain injury. The purpose of this study was to evaluate changes in alpha7* nAChr expression over a wider range of post-TBI recovery intervals. Animals were anesthetized and subjected to a moderate cortical contusion brain injury (2 mm cortical compression). Animals were euthanatized at various post-TBI time intervals, ranging from 1 h to 21 days, and quantitative autoradiography was used to evaluate cholinergic receptor subtype expression in the cerebral cortex and hippocampus. As previously reported, the alpha7* nAChr was the most sensitive target of TBI-induced plasticity. Significant decreases in alpha-[(125)I]-bungarotoxin (BTX) binding occurred as early as 1 h post-TBI, and persisted in some brain regions for up to 21 days. A kinetic analysis of changes in BTX binding, performed 2 days following brain injury, indicated that the binding deficits are not due to significant changes in receptor affinity. TBI-induced changes in alpha3*/alpha4* nACh receptors, muscarinic cholinergic receptors, and NMDA-type glutamate receptor expression were lower in magnitude, restricted to fewer brain regions and more transient in nature. Persistent deficits in alpha7* nAChr expression following TBI may contribute to impaired functional outcome following brain injury.

Animals↗

PubMed2002

Early effects of tribromoethanol, ketamine/xylazine, pentobarbitol, and isoflurane anesthesia on hepatic and lymphoid tissue in ICR mice.

We investigated the effects of various anesthetic agents on hepatic and splenic injury in mice. Three and six hours after intraperitoneal injection of TBE, intramuscular injection of ketamine/xylazine combination (K/X), intraperitoneal injection of pentobarbital (PB), and inhalation of isoflurane (IF), or intraperitoneal and intramuscular injection of control saline, mice were exsanguinated and serum was obtained for measurement of hepatic aspartate transaminase (AST), alanine transaminase (ALT) and gamma-glutamyltransferase (GGT). The spleen and liver also were obtained, and sections were examined by use of routine light microscopy for pathologic changes and for apoptosis, as determined by use of the in situ terminal deoxynucleotidyl transferase-mediated dUPT nick-end-labeling (TUNEL) histochemical analysis. Three hours after TBE or K/X administration, AST activity increased three- to fourfold above that in untreated and saline-injected control animals, and remained high at six hours. Administration of PB did not effect AST activity at three hours, but there was a significant increase at six hours. Activity of ALT was non-significantly increased three hours after TBE and K/X, but not PB administration. Administration of IF had no effect on hepatic enzyme activities, and GGT was not increased after administration of any of the agents. Markedly increased apoptosis was observed in splenic follicles and in hepatic Kupffer and endothelial cells at three hours after TBE and K/X administration, but apoptosis decreased to control levels by six hours. Increased apoptosis was not observed after IF administration. Administration of TBE and K/X causes injury to lymphocytes and to hepatic Kupffer and endothelial cells within three hours, and PB administration induces changes within six hours. Thus, use of these anesthetic agents should be avoided when experiments are being designed to test short-term effects of an experimental intervention on the spleen and possibly on all lymphoid tissues. In addition, they also should be avoided in experiments testing effects on hepatic tissue.

Alanine Transaminase↗