TY - CHAP
T1 - Statin-induced T-lymphocyte modulation and neuroprotection following experimental subarachnoid hemorrhage
AU - Ayer, Robert E.
AU - Ostrowski, Robert P.
AU - Sugawara, Takashi
AU - Ma, Qingy
AU - Jafarian, Nazanin
AU - Tang, Jiping
AU - Zhang, John H.
N1 - Funding Information:
This study was supported by grants (NS053407) from the National Institutes of Health to J.H.Z.
PY - 2013
Y1 - 2013
N2 - Introduction: Statins influence immune system activities through mechanisms independent of their lipid-lowering properties. T cells can be subdivided based on cytokine secretion patterns into two subsets: T-helper cells type 1 (Th1) and type 2 (Th2). Independent laboratory studies have shown statins to be potent inducers of a Th2 switch in immune cell response and be neuroprotective in several models of central nervous system (CNS) disease. This study was the first to evaluate the immune modulating effects of statins in subarachnoid hemorrhage (SAH). Methods: Simvastatin was administered to rats intraperitoneally in two dosages (1 and 20 mg/kg) 30 min after the induction of SAH using endovascular perforation. Neurological scores were assessed 24 h later. Animals were then sacrificed, and samples of cortex and brain stem were tested for expression of the T-regulatory cell cytokine transforming growth factor (TGF) β1, as well as interleukin (IL) 1β, a proinflammatory cytokine associated with Th1 immune responses. The presence of TGF-β1 secreting T cells was evaluated with the use of brain slices. Results: SAH significantly impaired neurological function in all SAH groups (treated and untreated) versus sham. Animals treated with high-dose simvastatin had less neurological impairment than both untreated and low-dose groups. Cortical and brain-stem levels of TGF-β1 were significantly elevated following SAH in the high-dose group. IL-1β was significantly elevated following the induction of SAH but was inhibited by high-dose simvastatin. Double-labeled fluorescent immunohistochemical data demonstrated the presence of lymphocytes in the subarachnoid and perivascular spaces following SAH. Expression of TGF-β1 by lymphocytes was markedly increased following treatment with high-dose simvastatin. Conclusion: The present study elucidated the potential role of a Th2 immune switch in statin provided neuroprotection following SAH. © 2013 Springer-Verlag Wien.
AB - Introduction: Statins influence immune system activities through mechanisms independent of their lipid-lowering properties. T cells can be subdivided based on cytokine secretion patterns into two subsets: T-helper cells type 1 (Th1) and type 2 (Th2). Independent laboratory studies have shown statins to be potent inducers of a Th2 switch in immune cell response and be neuroprotective in several models of central nervous system (CNS) disease. This study was the first to evaluate the immune modulating effects of statins in subarachnoid hemorrhage (SAH). Methods: Simvastatin was administered to rats intraperitoneally in two dosages (1 and 20 mg/kg) 30 min after the induction of SAH using endovascular perforation. Neurological scores were assessed 24 h later. Animals were then sacrificed, and samples of cortex and brain stem were tested for expression of the T-regulatory cell cytokine transforming growth factor (TGF) β1, as well as interleukin (IL) 1β, a proinflammatory cytokine associated with Th1 immune responses. The presence of TGF-β1 secreting T cells was evaluated with the use of brain slices. Results: SAH significantly impaired neurological function in all SAH groups (treated and untreated) versus sham. Animals treated with high-dose simvastatin had less neurological impairment than both untreated and low-dose groups. Cortical and brain-stem levels of TGF-β1 were significantly elevated following SAH in the high-dose group. IL-1β was significantly elevated following the induction of SAH but was inhibited by high-dose simvastatin. Double-labeled fluorescent immunohistochemical data demonstrated the presence of lymphocytes in the subarachnoid and perivascular spaces following SAH. Expression of TGF-β1 by lymphocytes was markedly increased following treatment with high-dose simvastatin. Conclusion: The present study elucidated the potential role of a Th2 immune switch in statin provided neuroprotection following SAH. © 2013 Springer-Verlag Wien.
KW - Early brain injury
KW - Endovascular perforation model
KW - Simvastatin
KW - Subarachnoid hemorrhage
KW - TGF-β1
KW - Th2 lymphocytes
KW - Th3 lymphocytes
KW - Transforming Growth Factor beta/metabolism
KW - Rats
KW - Male
KW - Neuroprotective Agents/pharmacology
KW - Rats, Sprague-Dawley
KW - T-Lymphocytes, Helper-Inducer/drug effects
KW - Brain/drug effects
KW - Dose-Response Relationship, Drug
KW - Animals
KW - Neurologic Examination
KW - Analysis of Variance
KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology
KW - Cytokines/metabolism
KW - Disease Models, Animal
KW - Subarachnoid Hemorrhage/drug therapy
UR - https://www.scopus.com/pages/publications/85052608539
UR - https://www.scopus.com/pages/publications/85052608539#tab=citedBy
UR - https://www.mendeley.com/catalogue/a2f051b1-3e2f-3636-a2ab-5bc68dd9b0a6/
U2 - 10.1007/978-3-7091-1192-5_46
DO - 10.1007/978-3-7091-1192-5_46
M3 - Chapter
C2 - 22890678
SN - 9783709111918
SN - 978-3-7091-1739-2
T3 - Acta Neurochirurgica, Supplementum
SP - 259
EP - 266
BT - Cerebral Vasospasm
PB - Springer Vienna
ER -