The Kinetics of Lymphocyte Subsets and Macrophages in Subarachnoid Space After Subarachnoid Hemorrhage in Rats

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Abstract

Background and Purpose

Although it has been suggested that humoral immunity plays a role in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage, there has been no quantitative assay for cellular immunity. We studied the kinetics of immune cells in the subarachnoid space after subarachnoid hemorrhage in the rat.

Methods

One hundred fourteen Sprague-Dawley rats were used in this study. The animals were divided into two groups and injected with either autologous blood (03 mL) or saline into the major cistern. They were killed at the specified time: 10 minutes or 1, 2, 3, 5, or 7 days after subarachnoid hemorrhage. For immunohistochemical analysis, the rats' whole brains were frozen, and cryostat sections were prepared. For flow cytometric analysis of immune cell presence, their whole brains underwent enzymatic digestion.

Results

Histopathologic study revealed pathological change of the arterial wall, and immunohistochemical study revealed the existence of macrophages and T cells in the subarachnoid space in animals with a survival time of 2 to 5 days after subarachnoid hemorrhage. A flow cytometric study revealed the peak of appearance of T cells and macrophages 2 days after subarachnoid hemorrhage. The helper-suppressor T cell ratio also reached a peak 2 days after subarachnoid hemorrhage.

Conclusions

A serial response of immunoreactive cells, which resembles that of the chronic allergic reaction observed in autoimmune diseases or delayed-type hypersensitivity, exists in the subarachnoid space after subarachnoid hemorrhage. The present results suggest that the initial response in cellular immunity, which is followed by humoral immunity and eicosanoid reactions, plays a role in eliciting the development of cerebral vasospasm.

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