Conclusion
The present study elucidated the potential role of a Th2 immune switch in statin provided neuroprotection following 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.