Introduction: Despite the success of rtPA and thrombectomy stroke continues to be a major disease burden to our society. Preventing secondary brain injury after stroke, given the broad therapeutic window, has gained increasing interest. It has been hypothesized that immunological processes substantially contribute to secondary brain damage. Indeed, the outcome of stroke in immunodeficient animals is more favorable compared to that in their immunocompetent counterparts. Here, we followed the evolution of stroke in the presence vs. absence of lymphocytes using serial MRI and T2 measurements.
Methods: Adult immunodeficient rag2-/- mice (n=6) and immunocompetent BALB/c mice (n=6) were subjected to stroke by intracerebral injection of 0.5 μl of 5 mM ouabain. Brain T2 relaxation times were measured using an 11.7T scanner at 1, 5, and 16 days following stroke induction. Post-mortem analysis of tissue sections included H&E and immunohistochemical staining for myelin basic protein, neurofilament, CD8, and CD68.
Results: While the increase in T2 values was identical for immunocompetent and immunodeficient animals one day post-stroke (70.88±4.58 vs. 69.88±1.78 ms, respectively, p=0.72), the normalization of the T2 relaxation time (“fogging effect”) proceeded faster in immunodeficient animals over the next few days. Over five days, T2 relaxation times decreased in both groups, but it was significantly shorter in immunodeficient animals compared to immunocompetent animals (41.88±3.68 vs. 59.91±14.95 ms, respectively; p<0.001). On day 16, the T2 relaxation time decreased further in both groups and the difference between infarcted area in immunodeficient and immunocompetent animals as well as healthy tissue was no longer observed. Post-mortem analysis revealed a better preservation of infarcted tissue in immunodeficient animals.
Conclusions: In immunodeficient rag2-/- mice, the restoration of T2 relaxation times in the brain is faster and translates into less profound destruction of brain tissue within stroke lesions. We hypothesize that T2 relaxation time can be used for assessment of immunotherapies aimed at the reduction of secondary brain injury in stroke victims.