dynorphins and Brain-Edema

The potential neuroprotective efficacy of dynorphin A antiserum on BBB dysfunction, edema formation and brain pathology was examined in a closed head injury (CHI) model in the rat. The CHI was produced by an impact of 0.224 N on the right parietal bone under anesthesia by dropping a weight of 114.6 g on the skull from a height of 20 cm through a guide tube. This concussive brain injury resulted in profound BBB disruption as evidenced by leakage of Evans blue and radioiodine in the brain. Edema formation and swelling at 5 h were most pronounced in the contralateral cerebral hemisphere. Pretreatment with dynorphin A antiserum (1:20, monoclonal) infused into the left lateral cerebral ventricle (30 microL in PBS) either 30 min before or 30 min after CHI significantly attenuated BBB dysfunction, brain edema formation, volume swelling and brain pathology. However, no reduction in brain edema, BBB permeability or improved brain pathology was seen when the antiserum was given 60 min post-CHI. These observations are the first to suggest that antiserum to dynorphin when administered into the CSF during early phase of CHI is neuroprotective. Our work further indicates that dynorphin is actively involved in the cellular and molecular mechanisms of edema formation and BBB breakdown in CHI.

Topics: Analysis of Variance; Animals; Antibodies; Blood-Brain Barrier; Brain Edema; Disease Models, Animal; Dynorphins; Head Injuries, Closed; Male; Rats

To study the secondary pathological changes in the central nervous system after injury and the role of dynorphin A1-13 in hypoxi-ischemic brain injury in neonatal rats.. Changes of concentrations of dynorphin A1-13 immunoreactives in some brain areas at different times after brain injury and the effect of injecting 8 microliters dynorphin A1-13 anti-serum into the medulla pool on pathological process of brain injury were observed in perinatal cerebral hypoxia ischemic rat models prepared by permanent ligation of right common carotid artery combined with a temporary systematic hypoxia at 37 degrees C in 7 day old Wistar rats.. Concentrations of dynorphin A1-13 in cortex, hypothalamus and hippocampus increased significantly after the injury. Microinjection of anti-dynorphin A1-13 serum into the medulla pool 1 h preinjury might markedly reduce brain edema and improve the physiological condition.. Dynorphin A1-13 plays a role in the pathophysiological process of brain hypoxia-ischemia and excessive amount of dynorphin A1-13 had some detrimental effect on the process.

Topics: Animals; Animals, Newborn; Brain; Brain Edema; Brain Ischemia; Dynorphins; Female; Hypoxia, Brain; Immune Sera; Male; Peptide Fragments; Rats; Rats, Wistar