Neuroprotection with an Erythropoietin Mimetic Peptide (pHBSP) in a Model of Mild Traumatic Brain Injury Complicated by Hemorrhagic Shock

Pyroglutamate helix B surface peptide (pHBSP) is an 11 amino acid peptide, designed to interact with a novel cell surface receptor, composed of the classical erythropoietin (EPO) receptor disulfide linked to the beta common receptor. pHBSP has the cytoprotective effects of EPO without stimulating erythropoiesis. Effects on early cerebral hemodynamics and neurological outcome at 2 weeks post-injury were compared in a rat model of mild cortical impact injury (3m/sec, 2.5 mm deformation) followed by 50 min of hemorrhagic hypotension (MAP 40 mm Hg for 50 min). Rats were randomly assigned to receive 5000 U/kg of EPO, 30 μg/kg of pHBSP, or an inactive substance every 12 h for 3 days, starting at the end of resuscitation from the hemorrhagic hypotension, which was 110 min post-injury. Both treatments reduced contusion volume at 2 weeks post-injury, from 20.8±2.8 mm3 in the control groups to 7.7±2.0 mm3 in the EPO-treated group and 5.9±1.5 mm3 in the pHBSP-treated group (p=0.001). Both agents improved recovery of cerebral blood flow in the injured brain following resuscitation, and resulted in more rapid recovery of performance on beam balancing and beam walking tests. These studies suggest that pHBSP has neuroprotective effects similar to EPO in this model of combined brain injury and hypotension. pHBSP may be more useful in the clinical situation because there is less risk of thrombotic adverse effects

Parental control styles and creative problem-solving abilities in children with vision impairment

Vision is an extremely important sense mode for learning. A great deal of learning takes place through the use of the visual modality. Therefore, children with vision impairment miss many valuable opportunities for learning and development.\ud \ud The research reported in this thesis is an exploration of parental styles of control and teaching styles and children's creative problem-solving abilities in Australia and Gujarat (India). The children in the study were children with sight and vision impairment (Australia) and children with vision impairment across two cultures (Australia and Gujarat) in the age group of 7 to 12 years. The aims of the two studies were to investigate the relationship of parental styles of control and teaching styles to children's performance on creative problem-solving tasks and to examine similarities and differences in the parenting styles of control and teaching styles of parents in Australia and Gujarat.\ud \ud This study provided findings from research undertaken in Brisbane (Australia) and in Gujarat (India). The Australian study provided a comparison of outcomes on creative problem-solving tasks by 11 sighted children and 17 children with varying degrees of vision impairment. The inclusion of 13 children with vision impairment from Gujarat (India), provided further comparison and consideration of cultural aspects of parental control and teaching style.\ud \ud The creative problem-solving tasks covered problems that involved concrete materials and problems that involved verbal information. These tasks were further subdivided into open-ended and goal-directed problems. In the open-ended problem, the children were required to generate as many responses as possible to the problem, whereas in the goal-directed problem, children were required to generate one or more creative solutions to the problem.\ud \ud Qualitative data were obtained and analysed from the parents of the children in each of the three groups through the use of questionnaire and semi-structured interview. The questionnaire provided reported information about parental styles of control and teaching style. Interviews with the parents provided information about their child's development and about their parental styles of control and teaching styles.\ud \ud Results from these studies indicated that sighted children managed the creative problem-solving tasks more easily and successfully than a matched sample of Australian children with vision impairment. The comparison of outcomes between the Australian and Gujarati children with vision impairment showed different levels of performance in favour of the Australian children. Children who scored high on their creative problem-solving tasks enjoyed the effects of early interaction with their parents, and of exploring the environment in order to understand their world.\ud \ud Reported information from interviews and questionnaires indicated that children of parents with permissive styles of parenting tended to be more successful in generating creative solutions to the tasks. Consideration of cultural and environmental features indicated that the children of the Gujarati sample had fewer resources available to them. The findings generally supported the need for parents of children with vision impairment to be active in assisting their children to become independent.\ud \ud The study also reports a number of methodological issues to be considered when undertaking this kind of research with subjects in widely varying cultures and environments

Improved Cerebrovascular Function and Reduced Histological Damage with Darbepoietin Alfa Administration after Cortical Impact Injury in Rats

Darbepoetin alfa (darbEpo) is an erythropoietic glycoprotein that activates the erythropoietin receptor. The aim of our study was to determine whether darbEpo is neuroprotective in a cortical impact injury (CII) model and to determine the characteristics of dose response and time window. To better understand the vascular mechanism of darbEpo neuroprotection, the reactivity of cerebral blood flow (CBF) to l-arginine administration was also studied. Rats were given saline or darbEpo from 2.5 to 50 μg/kg at 5 min after CII or a dose of 25 μg/kg darbEpo at times ranging from 5 min to 24 h after CII. Histological assessment was determined 2 weeks after a severe CII. Other rats were given either darbEpo (25 μg/kg) or saline daily for 3 days before injury. Five minutes after severe CII, they were given either l-arginine or d-arginine. Hemodynamic variables were monitored for 2 h after injury. In the dose-response study, darbEpo in doses of 25 and 50 μg/kg significantly reduced contusion volume from 39.1 ± 6.7 to 8.1 ± 3.1 and 11.2 ± 6.0 mm3, respectively. In the time window study, darbEpo reduced contusion volume when given in a dose of 25 μg/kg at 5 min to 6 h after the impact injury. In animals pretreated with darbEpo, the CBF response to l-arginine was significantly greater than in the animals pretreated with saline. These data demonstrate that darbEpo has neuroprotective effects in traumatic brain injury in a dose- and time-dependent manner and that vascular effects of darbEpo may have a role in neuroprotection