Inducible nitric oxide production and expression of transforming growth factor-beta1 in serum and CSF after cerebral ischaemic stroke in man.
A residual blood supply to the ischaemic brain is a crucial determinant for tissue survival. Early changes in the vascular network and subsequent angiogenesis may be mediated by short-lived molecules like nitric oxide (NO) or growth factors such as transforming growth factor-beta1 (TGF-beta1). Although TGF-beta1 can inhibit NO production, this interaction has not been studied after ischaemia in humans. Serum samples were taken from patients at 24 h and 6 months and cerebrospinal fluid (CSF) samples at 24 h and 1 week later for possible correlation between the two factors. Tissue expression of TGF-beta1 and of the inducible isoform of NO synthase (NOS2) was assessed by immunohistochemistry. CSF levels of NO2-/NO3- as well as total (active + latent) TGF-beta1 were higher in stroke patients as compared to controls 24 h after the stroke. Both NO2-/NO3- and TGF-beta1 were lower 6 months after the stroke compared to 24 h. Levels of NO2-/NO3- correlated with levels of TGF-beta1 within the time points (P = 0.041, Kendall correlation coefficient). There was a strong staining for NOS2 in brain tissue sections in neurones, reactive astrocytes, infiltrating white blood cells, and endothelial cells of larger microvessels. TGF-beta1 expression was mainly limited to neurones and reactive astrocytes. These findings suggest that the interaction between TGF-beta1 and NOS2 might be important for angiogenesis after cerebral ischaemia and may indicate that TGF-beta1 is upregulated as a negative feedback response to elevated levels of NO.
Krupinski
J
J
Department of Neurology, Institute of Neurology, Jagiellonian University, Cracow, Poland. mdkrupin@cyf-kr.edu.pl
Vodovotz
Y
Y
Li
C
C
Slowik
A
A
Beevers
D
D
Flanders
K C
KC
Lip
G
G
Kumar
P
P
Szczudlik
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D016212:Transforming Growth Factor beta / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*
D016212:Transforming Growth Factor beta; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II