Sulforaphane enhances aquaporin-4 expression and decreases cerebral edema following traumatic brain injury.
Brain edema, the infiltration and accumulation of excess fluid causing an increase in brain tissue volume, often leads to a rise in intracranial pressure and is a key contributor to the morbidity and mortality associated with traumatic brain injury (TBI). The cellular and molecular mechanisms contributing to the development/resolution of TBI-associated brain edema are poorly understood. Aquaporin-4 (AQP4) water channel is expressed at high levels in brain astrocytes, and the bidirectional transport of water through these channels is critical for the maintenance of brain water homeostasis. By using a rodent injury model, we show that TBI decreased AQP4 level in the injury core and modestly increased it in the penumbra region surrounding the core. Postinjury administration of sulforaphane (SUL), an isothiocyanate present in abundance in cruciferous vegetables such as broccoli, attenuated AQP4 loss in the injury core and further increased AQP4 levels in the penumbra region compared with injured animals receiving vehicle. These increases in AQP4 levels were accompanied by a significant reduction in brain edema (assessed by percentage water content) at 3 days postinjury. These findings suggest that the reduction of brain edema in response to SUL administration could be due, in part, to water clearance by AQP4 from the injured brain.
Zhao
Jing
J
The Vivian L. Smith Center for Neurologic Research and Department of Neurobiology and Anatomy, The University of Texas Medical School, Houston, 77225, USA.
Moore
Anthony N
AN
Clifton
Guy L
GL
Dash
Pramod K
PK
D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism*; D015152:Blotting, Northern / Q000379:methods; D001834:Body Water / Q000187:drug effects; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology*; D001930:Brain Injuries / Q000150:complications* / Q000188:drug therapy; D002452:Cell Count / Q000379:methods; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D007150:Immunohistochemistry / Q000379:methods; D017879:Isothiocyanates; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013454:Sulfoxides; D013861:Thiocyanates / Q000627:therapeutic use*; D013997:Time Factors
C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D005904:Glial Fibrillary Acidic Protein; D017879:Isothiocyanates; D012333:RNA, Messenger; D013454:Sulfoxides; D013861:Thiocyanates; C016766:sulforaphane