Hypertonic saline attenuates tissue loss and astrocyte hypertrophy in a model of traumatic brain injury.
Hypertonic saline is currently being used in the treatment of patients with post-traumatic cerebral edema and elevated intracranial pressure resulting from TBI. A limited number of studies show the cellular effects of hypertonic saline and no studies, to our knowledge, have investigated the effects on astrocytes. The role of astrocyte responses after traumatic brain injury remains unclear. There is evidence that reduced astrocyte proliferation is detrimental while increased hypertrophy and proliferation are signs of increased injury severity. Therefore, this study focused on the hypothesis that hypertonic saline-induced improvements in histological outcome are time dependent and may be associated with alterations in astrocyte hypertrophy after cortical contusion injury. Histopathological changes at 7 days after controlled cortical impact (CCI) injury were examined. Brain tissue loss determined using cresyl violet staining and astrocyte hypertrophy and proliferation were assessed using glial fibrillary acidic protein immunostaining in hypertonic saline and normal saline treated rats, and untreated, injured controls. Effects of the timing of hypertonic saline treatment administration on tissue loss were also examined. Plasma osmolarity and sodium levels were measured over 4 h and again at 24 h following hypertonic saline administration. Results show that hypertonic saline treatment reduced tissue loss that correlated with attenuated astrocyte hypertrophy characterized by reductions in astrocyte immunoreactivity without changes in the number of astrocytes after CCI injury. Delayed treatment of hypertonic saline resulted in the greatest reduction in tissue loss compared to all other treatments indicating that there is a therapeutic window for hypertonic saline use after traumatic brain injury.
Elliott
Melanie B
MB
Department of Neurosurgery, Thomas Jefferson University, 1025 Walnut Street, Philadelphia, PA 19107, USA. melaniedion@comcast.net
Jallo
Jack J
JJ
Barbe
Mary F
MF
Tuma
Ronald F
RF
D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049108:Cell Enlargement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009048:Motor Skills / Q000187:drug effects; D009994:Osmolar Concentration; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012462:Saline Solution, Hypertonic / Q000627:therapeutic use*; D013194:Staining and Labeling; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein; D012462:Saline Solution, Hypertonic