Dynamic expression of the suppressor of cytokine signaling-3 and cytokines in the cerebral basilar artery of rats with subarachnoid hemorrhage, and the effect of acetylcholine.
BACKGROUND
There are complex interactions between acetylcholine (ACh), the suppressor of cytokine signaling-3 (SOCS-3), and cytokines, however, little is known about their dynamic expression or their effects on cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). Therefore, we aimed to describe and clarify the dynamic expression of SOCS-3 and cytokines after SAH, as well as the relationships between the levels of SOCS-3, cytokines, and ACh.


METHODS
The rat model of single cisterna magna injection was used to mimic acute SAH. The degree of CVS was indicated by lumen diameter and artery wall thickness under H&E staining. A semi-quantitative immunohistochemical analysis method was used to clarify the role of SOCS-3 in the CVS after SAH. We also measured the content of IL-6 and IL-10 in cerebrospinal fluid.


RESULTS
We found that SOCS-3 expression levels increased rapidly within 12 h after SAH, more slowly after 12 h, and did not reach a peak within 48 h. Interleukin 6 (IL-6) levels rapidly increased within 24 h after SAH, reached a peak 24 h after SAH, and decreased slightly at 48 h. IL-10 levels increased during the first 6 h after SAH, after which this increase tapered off. ACh treatment reduced IL-6 levels and resulted in elevated levels of SOCS-3, but had no effect on IL-10 expression. Furthermore, ACh treatment relieved basilar arterial vasospasm, whereas mecamylamine pretreatment counteracted the activity of ACh.


CONCLUSIONS
Taken together, these data indicate that SOCS-3 was involved in vasospasm via an IL-6- and IL-10-related mechanism, and that CVS following SAH could be reversed by the intraventricular injection of ACh.
Department of Neurosurgery, The First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi' an, Shaanxi, People's Republic of China, jinningsong@126.com.
Jin-Ning
JN
Song
Ming
M
Zhang
Dan-Dong
DD
Li
Min
M
Li
Ji-Yang
JY
An
Mao-Feng
MF
Cheng
Xiao-Ye
XY
Guo
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism*; D002946:Cisterna Magna; D016207:Cytokines; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D016753:Interleukin-10 / Q000134:cerebrospinal fluid* / Q000378:metabolism; D015850:Interleukin-6 / Q000134:cerebrospinal fluid* / Q000378:metabolism; D008297:Male; D051381:Rats; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000378:metabolism*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000187:drug effects / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D020301:Vasospasm, Intracranial / Q000209:etiology / Q000378:metabolism*
D016207:Cytokines; D015850:Interleukin-6; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014665:Vasodilator Agents; D016753:Interleukin-10; D000109:Acetylcholine