Plasma BDNF and PDGF-AA levels are associated with high TCD velocity and stroke in children with sickle cell anemia.
Sickle cell anemia (SCA) associated cerebrovascular disease includes vascular remodeling, abnormal cerebral blood flow (CBF) and infarction. We studied the relationships between plasma brain derived neurotropic factor (BDNF), platelet derived growth factors (PDGF-AA and -AB/BB) and high trans-cranial Doppler (TCD) velocity, an indication of CBF velocity. Baseline plasma samples from 39 children (19 SCA with abnormal/high TCD [SATCD], 13 SCA with normal TCD [SNTCD] and 7 healthy non-SCA), were assayed for BDNF, PDGF-AA and -AB/BB plus 11 other cytokines. The sensitivity, specificity and usefulness of these biomarkers for stroke prediction was investigated. All subject groups were of similar age and gender distribution. Mean BDNF was significantly higher among SATCD than SNTCD (p=0.004) as was mean PDGF-AA (p=0.001). Similarly, mean PDGF-AA was higher among SCA subjects who developed stroke than those who did not (p=0.012). Elevated BDNF and PDGF-AA were good predictors of the presence of abnormally high CBF velocity and were both associated with severity of anemia. Elevated PDGF-AA predicted risk for stroke development. Stroke incidence and high TCD velocity were associated with elevated BDNF and PDGF-AA. These findings suggest a role for BDNF and PDGF-AA in the patho-physiological mechanism of cerebrovascular disease in SCA.
Genomics and Hemoglobinopathies Training Program, Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, 720 Westview Drive SW, Atlanta, GA, USA. hhyacinth@msm.edu
Hyacinth I
HI
Hyacinth
Beatrice E
BE
Gee
Thomas V
TV
Adamkiewicz
Robert J
RJ
Adams
Abdullah
A
Kutlar
Jonathan K
JK
Stiles
Jacqueline M
JM
Hibbert
D000704:Analysis of Variance; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging; D000077214:Becaplermin; D015415:Biomarkers / Q000097:blood; D001783:Blood Flow Velocity; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D002560:Cerebrovascular Circulation; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011446:Prospective Studies; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D020521:Stroke / Q000097:blood* / Q000000981:diagnostic imaging / Q000209:etiology; D017585:Ultrasonography, Doppler, Transcranial / Q000379:methods*
D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C075278:platelet-derived growth factor A; C095477:platelet-derived growth factor AB; D000077214:Becaplermin