2001 Fiscal Year Final Research Report Summary
RESEARCH ON INFALMMATORY CYTOKINE CASCADE IN CEREBROSPINAL FLUID AFTER SUBARACHNOID HEMORRHAGE AND THE GENERATING MECHANISM OF NORMAL PRESSURE HYDROCEPHALUS
| Project/Area Number |
11470287
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Cerebral neurosurgery
|
|---|
| Research Institution | SHINSHU UNIVERSITY |
|---|
Principal Investigator |
TADA Tsuyoshi SHINSHU UNIVERSITY, UNIVERSlTY HOSPITAL, ASSISTANT PROFESSOR, 医学部・附属病院, 講師 (00236530)
|
|---|
| Project Period (FY) |
1999 – 2001
|
| Keywords | hydrocephalus / subarachnoid hemorrhage / transforming growth factor-β1 / mouse / rat / cytokine / ouabain / fibrosis |
|---|
| Research Abstract |
TGF-β1 is elevated in the cerebrospinal fluid ( CSF ) after subarachnoid hemorrhage ( SAH ), especially in the patients who later develop, communicating hydrocephalus. ( 1994 ) In this study, we examined the concentration of IL-1β, IL-6, TGF-β1 and CRP in CSF of the patients with SAH, and found that the CRP levels in hydrocephalic group were higher than those of nonhydrocephalic group like TGF-β1 levels. IL-6 concentration was maximal within a day after SAH, and it was secreted by neutrophils and monocytes. These results suggest that leukocytes in CSF after SAH played an important role on subarachnoid fibrosis by releasing IL-6 and TGF-β1. (2001)
Human recombinant TGF-β1 induces communicating hydrocephalus in mice. ( 1994 ) Intrathecal injection of autologous serum can induce a similar hydrocephalus, and is prevented by the rabbit anti-human TGF-β1 antibody. ( 1997 ) An electron microscopy examination revealed that many fibroblasts appeared in the subarachnoid space in the second week after injection, and subarachnoid fibrosis was found in the third week. (1998) To assess CSF flow of the hydrocephalic mice, Indian ink was injected into the passage pathway and the time taken for the ink to pass from the parietal subarachnoid space to cervical lymph nodes. The study revealed a significant lengthening of the ink passage time due to altered CSF flow dynamics, while a histological examination showed ink stasis in the altered subarachnoid space compared to control mice. ( 1999) We also found that TGF-β1-injected rats clearly exhibited impaired spatial learning ability, but they did not exhibit ventricular dilatation. Histological examinations revealed subarachnoid fibrosis. The present and previous results suggest that subarachnoid fibrosis is not only an important factor to generate hydrocephalus, but also important in disturbance of the spatial learning ability.
|
