Stroke is the most prevalent cardiovascular disease worldwide, and is still one of the leading causes of death and disability. Stem cell-based therapy is actively being investigated as a new potential treatment for certain neurological disorders, including stroke. Various types of cells, including bone marrow mononuclear cells, bone marrow mesenchymal stem cells, dental pulp stem cells, neural stem cells, inducible pluripotent stem cells, and genetically modified stem cells have been found to improve neurological outcomes in animal models of stroke, and there are some ongoing clinical trials assessing their efficacy in humans. In this review, we aim to summarize the recent advances in cell-based therapies to treat stroke.

Background: Because of the aging of the Japanese population, traumatic brain injuries (TBI) have increased in elderly adults. However, the effectiveness and prognosis of intensive treatment for geriatric TBI have not yet been determined. Thus, we used nationwide data from the Japan Neurotrauma Data Bank (JNTDB) projects to analyze prognostic factors for intensive and aggressive treatments. Methods:We analyzed 1,879 geriatric TBI cases (age !65 years) registered in four JNTDB projects: Project 1998 (P1998) to Project 2015 (P2015). Clinical features, use of aggressive treatment, and 6-month outcomes on the Glasgow Outcome Scale (GOS) were compared among study projects. Logistic regression was used to identify prognostic factors in aggressively treated patients. Results:The percentage of geriatric TBI cases significantly increased with time-P1998: 30.1%; Project 2004 (P2004): 34.6%; Project 2009 (P2009): 43.9%; P2015: 53.6%, p<0.0001). Use of aggressive treatment also significantly increased, from 67.0% in P1998 to 69.3% in P2015 (p<0.0001). Less invasive methods, such as trepanation and normothermic targeted temperature management, were more often chosen for geriatric patients. These efforts resulted in a significant decrease in the 6-month mortality rate, from 76.2% in P1998 to 63.1% in P2015 (p=0.0003), although the percentage of severely disabled patients increased, from 8.9% in P1998 to 11.1% in P2015 (p=0.0003). Intraventricular hemorrhage was the factor most strongly associated with unfavorable 6-month outcomes (OR 3.79, 95% CI 1.78-8.06, p<0.0001). Conclusions:Less invasive treatments reduced mortality in geriatric TBI but did not improve functional outcomes. Patient age was not the strongest prognostic factor; thus, physicians should consider characteristics other than age.

Human neural stem cells (hNSCs) transplantation in several brain injury models has established their therapeutic potential. However, the feasibility of hNSCs transplantation is still not clear for acute subdural hematoma (ASDH) brain injury that needs external decompression. Thus, the aim of this pilot study was to test feasibility using a rat ASDH decompression model with two clinically relevant transplantation methods. Two different methods, in situ stereotactic injection and hNSC-embedded matrix seating on the brain surface, were attempted. Athymic rats were randomized to uninjured or ASDH groups (F344/NJcl-rnu/rnu, n = 7–10/group). Animals in injury group were subjected to ASDH, and received decompressive craniectomy and 1-week after decompression surgery were transplanted with green fluorescent protein (GFP)-transduced hNSCs using one of two approaches. Histopathological examinations at 4 and 8 weeks showed that the GFP-positive hNSCs survived in injured brain tissue, extended neurite-like projections resembling neural dendrites. The in situ transplantation group had greater engraftment of hNSCs than matrix embedding approach. Immunohistochemistry with doublecortin, NeuN, and GFAP at 8 weeks after transplantation showed that transplanted hNSCs remained as immature neurons and did not differentiate toward to glial cell lines. Motor function was assessed with rotarod, compared to control group ( n = 10). The latency to fall from the rotarod in hNSC in situ transplanted rats was significantly higher than in control rats (median, 113 s in hNSC vs. 69 s in control, P = 0.02). This study first demonstrates the robust engraftment of in situ transplanted hNSCs in a clinically-relevant ASDH decompression rat model. Further preclinical studies with longer study duration are warranted to verify the effectiveness of hNSC transplantation in amelioration of TBI induced deficits.

Aim Alcohol‐related problems, including trauma, are a great burden on global health. Alcohol metabolism in the Japanese population is genetically inferior to other races. This study aimed to evaluate the effects of alcohol use among a Japanese severe blunt trauma cohort. Methods This retrospective observational study analyzed the data of trauma patients registered in the Japan Trauma Data Bank between 2004 and 2019. The primary outcome of this study was in‐hospital mortality. The lengths of hospital and intensive care unit stay were the secondary outcomes. Propensity score matching was used to adjust the anatomical severity and patient background to reduce the potential alcohol use bias. Results We analyzed 46,361 patients categorized into nondrinking ( n = 37,818) and drinking ( n = 8,543) groups. After a 1:1 propensity score matching ( n = 8,428, respectively), despite the Glasgow Coma Scale and Revised Trauma Score scores being significantly lower in the drinking group (14 vs. 13 and 7.84 vs. 7.55, P < 0.001, respectively) and intensive care unit length of stay being significantly longer in the drinking group (6 vs. 7 days, P = 0.002), in‐hospital mortality was significantly lower in the alcohol group (11.8% vs. 9.0%, P < 0.001) and there were no differences in the duration of hospital stay (19 vs. 19 days, P = 0.848). Conclusion Despite increasing physiological severity on admission, after adjusting for anatomical severity, alcohol consumption could be beneficial in severe blunt trauma patients as regards in‐hospital mortality.

Indocyanine green (ICG) is a cyanine dye useful for visualizing blood vessels; it has been developed for endoscopy and is used in skull base surgery. Endoscopy is widely used for hematoma removal after an intracerebral hemorrhage since it is minimally invasive and has a shorter operation time than craniotomy. However, with this technique the surgical field is limited and it is difficult to obtain an adequate orientation; thus, it is challenging to locate the bleeding point, and postoperative rebleeding has been reported. We performed intraoperative ICG near-infrared fluorescence imaging to locate the bleeding point. This purpose of this study was to evaluate the usefulness of ICG angiography during endoscopic hematoma removal in two patients, using two endoscope types and comparing their visualization of perforating branches during the procedure. ICG angiography was performed in two different cases of putaminal hemorrhage, using the SPIES NIR/ICG-System and IMAGE1 S Rubina (both KARL STORZ, Tuttlingen, Germany) at the intraoperative bleeding site. The intraoperative use of ICG allowed the clear visualization of the perforating branches and real-time confirmation of active bleeding. We could also distinguish an old hematoma from the active bleeding point. The IMAGE1 S Rubina has adequate brightness for contrast enhancement, allowing surgical manipulation simultaneously to the enhancement phase. ICG fluorescence angiography is useful to identify the damaged vessel and perform hemostasis. We expect other similar devices to be developed in the future, accompanied by flexible and thin rigid endoscopes.