Background and Purpose-Cell transplantation has been used to reduce behavioral deficit in cerebral ischemia. However, there is no report about cell transplantation in experimental intracerebral hemorrhage (ICH). We hypothesize that intravenously transplanted human neural stem cells (NSCs) can migrate and differentiate into neurons or glial cells, thereby improving functional outcome in ICH. Methods-Experimental ICH was induced by intrastriatal administration of bacterial collagenase in adult rats. One day after surgery, the rats were randomly divided into 2 groups to receive intravenously either immortalized Lac z-positive human NSCs (5ϫ10 6 cells in 500 L, nϭ12) or the same amount of saline (nϭ13). The animals were evaluated for 8 weeks with modified limb placing and rotarod tests. Transplanted NSCs were detected by X-gal histochemistry or -gal immunohistochemistry with double labeling of GFAP, NeuN, neurofilament, or CNPase. Results-Intravenously transplanted NSCs migrated selectively to the perihematomal areas and differentiated into neurons (Ϸ10% of -gal ϩ cells) and astrocytes (Ϸ75%). The NSC-transplanted group showed better functional performance on rotarod test after 2 weeks and on modified limb placing test after 5 weeks compared with the control group (PϽ0.05), and these effects persisted for up to 8 weeks. There was no difference in the final hemispheric area between the 2 groups. Conclusions-Intravenously transplanted NSCs can enter the rat brain with ICH, survive, migrate, and improve functional recovery. Transplantation of human NSCs can be used to restore neurological deficits in experimental ICH. (Stroke.
A considerable portion of autoimmune encephalitis (AE) does not respond to conventional immunotherapies and subsequently has poor outcomes. We aimed to determine the efficacy of tocilizumab, an anti-interleukin-6 antibody, in rituximab-refractory AE compared with other treatment options. From an institutional cohort of AE, 91 patients with inadequate clinical response to first-line immunotherapy and following rituximab were retrospectively reviewed. Patients were grouped according to their further immunotherapy strategies. Thirty (33.0 %) patients were included in the tocilizumab group, 31 (34.0 %) in the additional rituximab group, and 30 (33.0 %) in the observation group. Outcomes were defined as the favorable modified Rankin Scale scores (≤2) at 1 and 2 months from the initiation of each treatment strategy and at the last follow-up. Favorable clinical response (improvement of the modified Rankin Scale scores by ≥ 2 points or achievement of the mRS scores ≤ 2) at the last follow-up was also analyzed. The tocilizumab group showed more frequent favorable mRS scores at 2 months from treatment initiation and at the last follow-up compared with those at the relevant time points of the remaining groups. The majority (89.5 %) of the patients with clinical improvement at 1 month from tocilizumab treatment maintained a long-term favorable clinical response. No serious adverse effects of rituximab or tocilizumab were reported. Therefore, we suggest that tocilizumab might be a good treatment strategy for treating AE refractory to conventional immunotherapies and rituximab. The tocilizumab-mediated clinical improvement manifests as early at 1 month after treatment initiation.
This study provides Class IV evidence that rituximab improves mRS scores for patients with autoimmune limbic encephalitis who fail first-line therapy.
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