Dexmedetomidine renders a brain protection on hippocampal formation through inhibition of nNOS-NO signalling in endotoxin-induced shock rats.
BACKGROUND
Endotoxin shock (ES) and its severe complications, such as brain injury, remain a handicap clinically. Therefore, it is a clinical significance of developing a new drug to treat brain damage induced by ES.


OBJECTIVE
The present study aimed to observe the protective effect of dexmedetomidine (Dex) on hippocampal formation in endotoxin-induced shock rats and explore its possible mechanism.


METHODS
High and low doses of Dex were tail intravenously administered slowly. After a 5-minute interval, lipopolysaccharide was tail intravenous injected slowly to establish the ES rats. Six hours after Dex administration, these rats were immediately sacrificed. Then, the brain water content was determined. NO amounts in homogenate, cerebrospinal fluid and serum were detected by Griess Reagent assay. nNOS mRNA in hippocampal formation was measured by RT-PCR and nNOS protein was determined by Western blotting and immunohistochemistry.


RESULTS
ES rats showed that cerebral water contents were significantly increased, NO concentrations in brain tissues, serum and cerebrospinal fluid were each obviously raised and meanwhile expressions of nNOS mRNA and its protein in hippocampal formation were notably augmented. Treatment of these rats with Dex evidently decreased cerebral water contents, NO concentrations and nNOS mRNA and its protein expressions.


CONCLUSIONS
These results demonstrated that Dex exerted a brain protection on hippocampal formation through inhibition of the nNOS-NO signalling in ES rats and Dex may have a favourably therapeutic value in treating brain damage in patients with endotoxin shock.
Department of Anesthesiology, Children's Hospital of Fudan University , Shanghai , PR China and.
Bo
B
Xiong
Qi-qing
QQ
Shi
Chang-hong
CH
Miao
D000818:Animals; D015153:Blotting, Western; D001930:Brain Injuries / Q000188:drug therapy / Q000473:pathology*; D002352:Carrier Proteins / Q000187:drug effects*; D020927:Dexmedetomidine / Q000494:pharmacology*; D004731:Endotoxins; D006624:Hippocampus / Q000187:drug effects*; D008070:Lipopolysaccharides; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*
D002352:Carrier Proteins; D004731:Endotoxins; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; C488668:Zdhhc23 protein, rat; D020927:Dexmedetomidine
Animal models; basic science; drug use