T- and B-Cell-Deficient Mice with Experimental Stroke have Reduced Lesion Size and Inflammation

Abstract

Stroke induction in immunologically competent mice not only produces local ischemia and brain damage, but also induces early inflammatory changes in brain and peripheral immune responses. Although immune elements clearly are activated after brain vascular occlusion, the relative contribution of T and B lymphocytes to the developing lesion has not been quantified. We evaluated effects 22 h after middle cerebral artery occlusion (90 mins) on histologic injury and peripheral immune activation in severe combined immunodeficient (SCID) mice lacking T and B cells. Cortical and total infarct volumes were strikingly reduced in male SCID mice (n = 14, 3364% of contralateral cortex, n = 10, 5263% of contralateral hemisphere) versus immunologically intact C57BL/6 mice (wild type, n = 9, 5765% of contralateral cortex, 5764% of contralateral hemisphere) (P < 0.01). Striatal infarction was not altered (7767% of contralateral striatum in SCID, 8467% in wild type), suggesting that the core of the evolving ischemic lesion was not impacted by lack of T and B cells. As expected, inflammatory factors from immune cells in ischemic SCID brains were essentially absent, with the exception of interleukin-1b increase in both SCID and wild type tissue. Spleen cell numbers were low in SCID mice, but were further reduced 22 h after stroke, with substantial reduction in most inflammatory factors except for increased expression of interferon-c and macrophage inflammatory protein (MIP)-2. These data quantify the damaging effect of T and B lymphocytes on early, evolving ischemic brain injury, and further implicate interleukin-1b in brain and interferon-c and MIP-2 in spleen as inflammatory factors produced by cells other than T and B cells.

How and why do T cells and their derived cytokines affect the injured and healthy brain?

“…Furthermore, adding splenocytes to Rag −/− animals to repopulate the T cell and B cell compartments reverses the effect 5 . Similar results were obtained using severe combined immunodeficiency (SCID) mice (which also lack T cells and B cells) 6,7 .…”

The immune response after hypoxia-ischemia in a mouse model of preterm brain injury

“…For example, T-cell-deficient mice exhibit significant reductions in infarct volume [49,50] in rodent models of HI brain injury. T-cells and other peripheral immune cells were found to infiltrate into the neonatal rat brain and to remain there for hours to months following HI [51-53].…”

Pro-Inflammatory Interferon Gamma Signaling is Directly Associated with Stroke Induced Neurodegeneration

“…In the spleen, IP-10 mRNA levels are increased at 22 h post-MCAO (Offner et al 2006; Hurn et al 2007). Although IP-10 transcript has been measured at selected time points following stroke, IP-10 protein levels have not been quantified in the brain or spleen following MCAO or at longer time points after MCAO.…”