Relative effects of mannitol and hypertonic saline on calpain activity, apoptosis and polymorphonuclear infiltration in traumatic focal brain injury.
The purpose of this study was to compare the relative effects of mannitol and hypertonic saline (HTS) on calpain activity, apoptosis and neuroinflammatory response induced by experimental cortical contusion. Four groups of 5 Sprague-Dawley male rats were submitted to focal brain injury produced by exposing the parietal cortex to dynamic cortical deformation. Groups were defined by rescucitation fluids administered 30 min post-injury as follows: group 1-0.9% normal saline 2 ml/kg; group 2-mannitol 20% 0.5 g/kg; group 3-HTS 2 ml/kg; group 4-HTS 4 ml/kg. At 72 h, animals were sacrificed. Paraffin-mounted sections of were stained for mu-Calpain, TUNEL, active caspase 3 and myeloperoxidase. There was no difference in the lesion size between the different groups. In contrast, there was a significant reduction in calpain and apoptosis activity and in the neuroinflammatory response in animals receiving HTS. Although mannitol proved to significantly decrease the neuroinflammatory response and calpain activity, it did not affect apoptosis, and its effect was significantly less than that of HTS. Importantly, the effect of HTS was mostly independent from the infused volume. Our results show that HTS promotes cell survival and reduces secondary brain damage following TBI. This protective effect was evidenced at rather small infused volumes, proved to encompass several cellular and molecular mechanisms involved in secondary cell death and could not be related to relief of intracranial pressure. These findings suggest that the high osmolality of HTS may have protective effects besides its impact on brain edema.
Soustiel
Jean F
JF
Acute Brain Injury Research Laboratory and B. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. j_soustiel@rambam.health.gov.il
Vlodavsky
Eugene
E
Zaaroor
Menashe
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002154:Calpain / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D008297:Male; D008353:Mannitol / Q000008:administration & dosage*; D009504:Neutrophils / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage*
D012462:Saline Solution, Hypertonic; D008353:Mannitol; D002154:Calpain; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases