title: Characterization of regional cerebral blood flow and expression of angiogenic growth factors in the frontal cortex of juvenile male SHRSP and SHR.
abstract: Attention-deficit/hyperactivity disorder (AD/HD) is a common pediatric behavioral disorder associated with male preponderance and reduction of regional cerebral blood flow (rCBF). However, lack of an appropriate animal model exhibiting appropriate AD/HD symptoms stands in the way of studying mechanism(s) underlying reduced rCBF and male preponderance. Our group has been investigating the suitability of juvenile male stroke-prone spontaneously hypertensive rats (SHRSP), a substrain of the commonly used AD/HD animal model SHR, as a model for AD/HD because, unlike SHR, SHRSP displays cognitive impairment and male preponderance. Our more recent studies revealed alterations in the synthesis of sex steroid hormones and angiogenic factors in the frontal cortex of male SHRSP compared to the genetic control WKY. Based on these observations, the present study utilizes laser-Doppler flowmetry, histochemistry, enzyme immunoassay, immunoblotting, and real-time PCR to characterize and compare the patterns of regional cerebral blood flow and synthesis of angiogenic molecules [basic fibroblast growth factor; nitric oxide synthase isoforms (endothelial, neuronal and inducible); vascular endothelial growth factor (VEGF) and its signaling molecules (VEGF receptors, phosphorylated Akt, endothelial nitric oxide synthase eNOS] between male SHRSP and SHR. Overall, consistent with our previous data showing alteration in VEGF/Akt/NO signaling, there was a marked reduction in the profile of rCBF (35%) and angiogenic factors of SHRSP, compared to age-matched genetic control Wistar-Kyoto rats (WKY) and SHR. We conclude that, unlike SHR, the profiles of rCBF and angiogenic factors in SHRSP are altered in juvenile male. Thus, SHRSP appears to be a more suitable animal model for studying changes in rCBF in AD/HD.
authors.affiliation: Departments of Cardiovascular Medicine and Neuropharmacology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Subrina
authors.initials: S
authors.lastname: Jesmin
authors.forename: Hiroko
authors.initials: H
authors.lastname: Togashi
authors.forename: Chishimba N
authors.initials: CN
authors.lastname: Mowa
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Ueno
authors.forename: Taku
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Akiko
authors.initials: A
authors.lastname: Shibayama
authors.forename: Takashi
authors.initials: T
authors.lastname: Miyauchi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sakuma
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yoshioka
mesh_terms: D000367:Age Factors; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000503:physiopathology*; D015153:Blotting, Western; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D005625:Frontal Lobe / Q000098:blood supply* / Q000378:metabolism; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D016555:Matched-Pair Analysis; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012039:Regional Blood Flow; D013045:Species Specificity; D020521:Stroke / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D019001:Nitric Oxide Synthase