No description available.

Surgery-induced brain injury (SBI) refers to trauma caused by routine neurosurgical procedures that may result in post-operative complications and neurological deficits. Unlike accidental trauma, SBI is potentially subject to preemptive interventions at the time of surgery. SBI can cause bleeding, inflammation and the formation of tissue gaps. Conventional haemostatic techniques, though effective, are not necessarily conducive to healing. Inflammation and the absence of extracellular matrix in tissue gaps also hinder regeneration after SBI. This study investigated the applications of RADA16-I, a type I self-assembling peptide nanofibre scaffold (SAPNS), and mesenchymal stem cells (MSCs) in the treatment of SBI. Using animal SBI models, treatments were applied immediately and locally onto the operative fields, taking advantages of the haemostatic and cell-carrying properties of RADA16-I, the immune- modulatory effects of MSCs, and the earliest available therapeutic window for SBI. There were three objectives. Objective 1 was to compare RADA16-I with conventional haemostatic methods, including electrocautery and fibrin sealant, in their effects on the brain’s acute cellular inflammatory response. The hypothesis was that RADA16-I would cause the same or a lesser degree of inflammation. This study showed that RADA16-I was superior to electrocautery, and was noninferior to conventional topical haemostats. Objective 2 was to study the in vitro expansion of MSCs within RADA16-I in preparation for in vivo transplantation. The hypothesis was that the in vitro survival of MSCs would vary between different RADA16-I concentrations and culturing methods. This study showed that plating MSCs onto pre-buffered RADA16-I would protect the cells against RADA16-I’s intrinsic acidity and result in better initial survival. Subsequent integration with the RADA16-I hydrogel, however, was poor. Mixing the cells directly with RADA16-I caused initial cell loss but allowed better integration. RADA16-I at lower concentrations resulted in better survival but also more fragile hydrogels that were mechanically unfit for transplantation. Mixing MSCs with 0.5% RADA16-I for seven days represented a compromise between these competing factors. Objective 3 was to study the in vivo effects of a MSC-RADA16-I implant on tissue reactions after SBI. The hypothesis was that the combinatorial therapy would result in less cellular inflammatory response than MSC alone or RADA16-I alone. Implants of pre-buffered 0.5% RADA16-I hydrogel, with or without cells, were found to cause less inflammation than control. MSCs in free suspension resulted in significantly more pronounced inflammation than when carried in RADA16-I. Supplementing RADA16-I with MSCs, however, did not confer additional benefit over RADA16-I alone. The present study provided new preclinical evidence to support future clinical testing of RADA16-I as a novel surgical haemostat. It also demonstrated the feasibility of early intracerebral transplantation of RADA16-I hydrogel in the treatment of SBI. Whether RADA16-I and/or transplanted MSCs could modulate the brain’s inflammatory response after SBI require further investigations, which may include the search for the optimal ex vivo expansion technique and specifically tailored nanofibre scaffold. The translational applications of these findings would include the treatment of SBI over critical brain regions where trauma would cause severe functional deficits and where better healing would facilitate patient recovery. / published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

No description available.

No description available.

No description available.

No description available.

Thesis (M.S.)--University of Hawaii at Manoa, 2005. / Includes bibliographical references (leaves 37-41). / viii, 41 leaves, bound cil. ill. 29 cm

The effects of septal lesions in rats on the hyperglycaemic response to stress, adrenal weight and water intake were investigated. Tested four times post-operatively at approximately weekly intervals, septal rats did not manifest significantly different resting blood glucose levels than control animals nor did they demonstrate an abnormal degree of hyperglycaemia following periods of unavoidable foot shock. No adrenal hypertrophy was evident in septal subjects compared to controls. Daily water intake was significantly higher among septals. The results concerning blood sugar levels and adrenal weights are taken as evidence that septal rage may not represent true hyperemotionality since certain appropriate physiological concomitants are absent. A second experiment investigated resistance to capture and handling and aspects of open field behaviour in septal and control rats following injections of chlorpromazine hydrochloride or saline. Septalectomized rats resisted handling and capture to a greater extent than controls, traversed fewer squares and demonstrated less rears in an open field, and had a greater tendency to leave a home cage and enter an open field. Chlorpromazine affected neither control nor septal subjects except to suppress the tendency of septal rats to leave a home cage and enter an open field. The behaviour of septal rats is discussed in terms of apparent emotionality. / Arts, Faculty of / Psychology, Department of / Graduate

Not available / text

Digitized by Kansas Correctional Industries