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Biomedical subjects

K E Sloan

Publications and source records attributed to K E Sloan.

5 recordsLinked to original sources

Inhibition of alpha4 integrin protects against transient focal cerebral ischemia in normotensive and hypertensive rats.

BACKGROUND AND PURPOSE: The present study was performed to determine the role of alpha4 (CD49d), a member of the integrin family of adhesion molecules, in ischemic brain pathology. METHODS: Male spontaneously hypertensive rats (SHR) or Sprague-Dawley rats underwent 60-minute middle cerebral artery occlusion (MCAO) followed by 23-hour reperfusion. Animals were injected intravenously with 2.5 mg/kg anti-rat alpha4 antibody (TA-2) or isotype control antibody (anti-human LFA-3 IgG(1), 1E6) 24 hours before MCAO. Infarct volume was quantified by staining of fresh tissue with tetrazolium chloride and myeloperoxidase activity measured in SHR tissue homogenates 24 hours after MCAO. In SHR, mean arterial blood pressure was recorded before and after MCAO in animals treated with TA-2 and 1E6. Fluorescence-activated cell sorting analysis was performed on peripheral blood leukocytes before and after MCAO. RESULTS: TA-2 treatment significantly reduced total infarct volume by 57.7% in normotensive rats (1E6, 84.2+/-11.5 mm(3), n=17; TA-2, 35.7+/-5.9 mm(3), n=16) and 35.5% in hypertensive rats (1E6, 146.6+/-15.5 mm(3), n=15; TA-2, 94.4+/-25.8 mm(3), n=11). In both strains, TA-2 treatment significantly reduced body weight loss and attenuated the hyperthermic response to MCAO. In SHR, treatment with TA-2 significantly reduced brain myeloperoxidase activity. Resting mean arterial blood pressure was unaffected by treatment. Leukocyte counts were elevated in TA-2-treated rats. Fluorescence-activated cell sorting analysis demonstrated the ability of TA-2 to bind to CD3+, CD4+, CD8+, and CD11b+ cells in both naive animals and after MCAO. CONCLUSIONS: These data demonstrate that inhibition of alpha4 integrin can protect the brain against ischemic brain injury and implicate endogenous alpha4 integrin in the pathogenesis of acute brain injury. The mechanism by which alpha4 integrin inhibition offers cerebroprotection is independent of blood pressure modulation and is likely due to inhibition of leukocyte function.

Animals↗

Musculoskeletal effects of an electrical stimulation induced cycling programme in the spinal injured.

Twelve patients were involved in a 3 month stimulation induced cycling programme at the Royal Perth Rehabilitation Hospital. A number of the patients were less than 1 year post injury, all except one had an incomplete injury, and most were receiving physiotherapy. All patients who completed the programme increased their time of cycling and, in all but one case, the exercise load, indicative of a local training effect. Significant improvements were found in voluntary isometric strength, stimulated isometric strength and stimulated isometric endurance of the quadriceps, muscle grading of the quadriceps and biceps femoris and the cross-sectional areas of the quadriceps and total thigh muscle. No change was found in voluntary isokinetic strength of the quadriceps. All patients with incomplete injuries reported improvements in the activities of daily living (ADL) after the programme. Bone mineral density (BMD) was examined in two patients, one less than 1 year post injury, and one greater than 4 years post injury. The programme of cycling did not restore BMD in the latter patient. However, while the former patient still displayed a reduced BMD after the programme, it is unknown whether this loss of bone was retarded. This needs further investigation. This study demonstrates the effectiveness of a combined physiotherapy/cycling programme in the rehabilitation of people with spinal injuries. To be successful this type of programme has to be incorporated into the rehabilitation process, as has been done at the Sir George Bedbrook Spinal Unit.

Activities of Daily Living↗

A clinical exercise system for paraplegics using functional electrical stimulation.

A low cost clinical exercise system was developed for the spinal cord injured, based on a bicycle ergometer and electrical stimulation. A pilot project was conducted, using the system, to examine the effects of stimulation induced cycling in long term paraplegics. The project comprised 2 phases of exercise, a strengthening phase involving a 12 week programme of electrical stimulation to the quadriceps and hamstrings and a 12 week cycling phase. Physiological, morphological and biochemical parameters were measured for each subject, at the beginning of the programme and following each phase. Results showed that a programme of stimulation induced lower limb exercise increased the exercise tolerance of all patients, as determined by a progressive increase in exercise time, cycling rate and exercise load. The enhanced exercise tolerance was a result of increases in local muscle strength and endurance. Increases in thigh muscle area and joint range of motion were recorded and all incomplete subjects reported an improvement in functional capabilities and general wellbeing.

Adult↗

Qualitative and quantitative comparison of the distribution of phosphorylated and non-phosphorylated neurofilament epitopes within central and peripheral axons of adult hamster (Mesocricetus auratus).

The distribution of phosphorylated and non-phosphorylated neurofilament epitopes was determined immunocytochemically in adjacent 2 microns-thick sections of sciatic nerve, ventral root and spinal cord. Staining was scored as either intense, moderate or absent and the proportion of labeled axons was calculated for each category. Nearly all sciatic nerve and ventral root axons were immunoreactive with both antibodies against phosphorylated and non-phosphorylated neurofilaments and there were no significant differences in the number of intensely- or moderately-labeled axons. Within the spinal cord however, while the majority of large caliber axons was stained with both antibodies, there was a significant number of small caliber axons which stained only with antibodies against phosphorylated neurofilaments. These results show that phosphorylated and non-phosphorylated neurofilaments are extensively codistributed in CNS and PNS axons, and that in the CNS, staining intensity for non-phosphorylated epitopes is less in the smaller axons.

Animals↗

Differential distribution of phosphorylated and non-phosphorylated neurofilaments within the retina and optic nerve of hamsters.

Retinae and optic nerve sections from adult hamsters were reacted with antibodies against phosphorylated (P) or non-phosphorylated (NP) neurofilament proteins. NP epitopes were observed within ganglion cell bodies and extended into the proximal portion of the optic nerve. P epitopes became prominent within axons as they approached the optic disc and remained throughout the optic nerve. This spatial distribution appears similar to the pattern of myelination within this axonal population.

Animals↗