Background and Purpose-Intra-arterial cell transplantation offers a novel therapeutic strategy for stroke; however, it remains unclear how the timing of cell administration affects cell distribution, brain repair processes, and functional recovery. Here, we investigate the hypothesis that the timing of cell transplantation changes the behavior of the cell graft and the host environment in a way that affects functional recovery. Methods-Rats received human mesenchymal stem cells via the internal carotid artery at 1, 4, or 7 days (D1, D4, or D7) after middle cerebral artery occlusion and reperfusion. Animals were euthanized at various time points to assess cell distribution, infiltration of activated microglia, expression of brain-derived neurotrophic factor, reactive astrocytes, angiogenesis, and functional recovery. Results-Human mesenchymal stem cells were widely distributed both in the peri-infarct and core in D1, and dominantly in the peri-infarct in D4. Very few cells were observed on D7. At day 7 poststroke, microglia activation was significantly suppressed in both the peri-infarct and core in D1, and predominantly in the peri-infarct in D4. At day 21 poststroke, brain-derived neurotrophic factor was widely distributed throughout the peri-infarct in D1 and D4, along with many reactive astrocytes and considerable angiogenesis. Motor function improved earlier in D1 and later in D4, but no recovery was obtained in D7. Conclusions-Our

Cell transplantation therapy offers great potential to improve impairments after stroke. However, the importance of donor age on therapeutic efficacy is unclear. We investigated the regenerative capacity of transplanted cells focusing on donor age (young vs. old) for ischaemic stroke. The quantities of human mesenchymal stem cell (hMSC) secreted brain-derived neurotrophic factor in vitro and of monocyte chemotactic protein-1 at day 7 in vivo were both significantly higher for young hMSC compared with old hMSC. Male Sprague-Dawley rats subjected to transient middle cerebral artery occlusion that received young hMSC (trans-arterially at 24 h after stroke) showed better behavioural recovery with prevention of brain atrophy compared with rats that received old hMSC. Histological analysis of the peri-infarct cortex showed that rats treated with young hMSC had significantly fewer microglia and more vessels covered with pericytes. Interestingly, migration of neural stem/progenitor cells expressing Musashi-1 positively correlated with astrocyte process alignment, which was more pronounced for young hMSC. Aging of hMSC may be a critical factor that affects cell therapy outcomes, and transplantation of young hMSC appears to provide better functional recovery through anti-inflammatory effects, vessel maturation, and neurogenesis potentially by the dominance of trophic factor secretion.

Cell transplantation therapy for cerebral infarction has emerged as a promising treatment to reduce brain damage and enhance functional recovery. We previously reported that intra-arterial delivery of bone marrow mesenchymal stem cells (MSCs) enables superselective cell administration to the infarct area and results in significant functional recovery after ischemic stroke in a rat model. However, to reduce the risk of embolism caused by the transplanted cells, an optimal cell number should be determined. At 24 h after middle cerebral artery occlusion and reperfusion, we administered human MSCs (low dose: 1 × 10(4) cells; high dose: 1 × 10(6) cells) and then assessed functional recovery, inflammatory responses, cell distribution, and mortality. Rats treated with high- or low-dose MSCs showed behavioral recovery. At day 8 post-stroke, microglial activation was suppressed significantly, and interleukin (IL)-1β and IL-12p70 were reduced in both groups. Although high-dose MSCs were more widely distributed in the cortex and striatum of rats, the degree of intravascular cell aggregation and mortality was significantly higher in the high-dose group. In conclusion, selective intra-arterial transplantation of low-dose MSCs has anti-inflammatory effects and reduces the adverse effects of embolic complication, resulting in sufficient functional recovery of the affected brain.

ICG videoangiography provides different characteristics of bypass flow among adult MMD, pediatric MMD, and atherosclerosis. Poor run-off and stagnation of blood flow from the STA might contribute to postoperative HP in MMD. The occurrence of postoperative HP in MMD could depend on two factors: donor STA size and poor run-off and integrity of the blood brain barrier in the recipient MCA.

Background and Purpose— Malignant middle cerebral artery (MCA) infarction is one of the most devastating forms of ischemic stroke, and identification of predictors of a malignant course of the MCA or internal carotid artery (ICA) infarction is exceedingly important. Here, we investigated whether thrombus component defined with MR imaging could predict malignant changes in the acute stage of the cerebral infarction. Methods— We retrospectively analyzed 468 consecutive patients with cerebral infarction in our institute from 2007 to 2011. In all the patients, initial MR imaging including T2 star (T2*), diffusion weighted imaging (DWI), fluid-attenuated inversion recovery (FLAIR) and MR angiography were performed and susceptibility vessel sign (SVS) on T2* was evaluated in relation to the brain swelling on CT 24 hours after the initial imaging. Correlation of the thrombus component between MRI and CT was also evaluated. Results— One hundred and twelve patients showed MCA main trunk or carotid T occlusion. Among them, 38 patients were t-PA failed or did not undergo endovascular treatment. Twenty eight patients had ICA occlusion and 10 patients had MCA main trunk occlusion. SVS was apparent in 17 (45%) patients, and there was no significant difference between SVS positive and SVS negative group in age (75.6 vs. 72.3 years old), time to arrival (84.4 vs. 106.9 min) and NIH stroke scale (19.5 vs. 18.7). On the other hand, DWI area was significantly larger in SVS positive group (189.3 vs. 107.6 ml). DWI area was also significantly correlated with brain swelling 24 hour later regardless of SVS. Most SVS positive patients showed MCA dense sign on CT performed 24 hours later (85.7% vs. 29.4%). Conclusions— Susceptibility vessel sign on MRI, which suggests RBC rich thrombus, indicates early maturation of the infarct in the MCA area, but could not predict following malignant change.