TGF-beta 1 post-treatment in a rabbit model of cerebral ischaemia.
Transforming growth factor-beta 1 (TGF-beta 1), suggested in some studies to suppress astrocyte and neutrophil function, has also reduced ischaemic brain injury when administered immediately prior to clot embolization in models of thromboembolic stroke. The effect of TGF-beta 1 as a post-treatment paradigm was investigated in a rabbit model of thromboembolic stroke. Following clot embolization, regional cerebral blood flow fell to < 10 cc 100 g-1 min-1 in all animals. TGF-beta 1 (10 micrograms) or vehicle (n = 5 each group) was infused via the contralateral carotid artery. TGF-beta 1 administration resulted in a rapid and selective reduction in the peripheral neutrophil count as compared to a significant (p < 0.05) increase in control values (2336 +/- 817 vs 4320 +/- 928 neutrophils mm3, mean +/- SEM). Neutrophil aggregation was increased within 30 min of TGF-beta 1 infusion when compared to control (2.07 +/- 0.70 vs 1.09 +/- 0.17 ohms, p < 0.05); neutrophil chemiluminescence, an index of the oxygen respiratory burst was not significantly affected by TGF-beta 1 administration. No difference in platelet counts or aggregation was noted. There was no significant difference between the two groups regarding brain infarct size (47.5 +/- 10.9 vs 56.5 +/- 10.4, n = 4, TGF-beta vs control, mean +/- SEM), intracranial pressure, or brain excitatory amino acid levels (aspartate and glutamate) within ischaemic regions.(ABSTRACT TRUNCATED AT 250 WORDS)
Gross
C E
CE
Vermont Center for Vascular Research, Department of Medical Biostatistics, University of Vermont, Burlington 05405.
Howard
D B
DB
Dooley
R H
RH
Raymond
S J
SJ
Fuller
S
S
Bednar
M M
MM
D000704:Analysis of Variance; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology*; D002339:Carotid Arteries; D002449:Cell Aggregation / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D007839:Functional Laterality; D007261:Infusions, Intra-Arterial; D007427:Intracranial Pressure / Q000187:drug effects; D007958:Leukocyte Count / Q000187:drug effects; D008163:Luminescent Measurements; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D009195:Peroxidase / Q000097:blood; D010976:Platelet Count / Q000187:drug effects; D011817:Rabbits; D016897:Respiratory Burst / Q000187:drug effects; D013923:Thromboembolism / Q000188:drug therapy* / Q000503:physiopathology; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000627:therapeutic use*
D016212:Transforming Growth Factor beta; D009195:Peroxidase