Radiation therapy is an indispensable therapeutic modality for various brain diseases. Though endogenous neural stem cells (NSCs) would provide regenerative potential, many patients nevertheless suffer from radiation-induced brain damage. Accordingly, we tested beneficial effects of exogenous NSC supplementation using in vivo mouse models that received whole brain irradiation. Systemic supplementation of primarily cultured mouse fetal NSCs inhibited radiation-induced brain atrophy and thereby preserved brain functions such as short-term memory. Transplanted NSCs migrated to the irradiated brain and differentiated into neurons, astrocytes, or oligodendrocytes. In addition, neurotrophic factors such as NGF were significantly increased in the brain by NSCs, indicating that both paracrine and replacement effects could be the therapeutic mechanisms of NSCs. Interestingly, NSCs also differentiated into brain endothelial cells, which was accompanied by the restoration the cerebral blood flow that was reduced from the irradiation. Inhibition of the VEGF signaling reduced the migration and trans-differentiation of NSCs. Therefore, trans-differentiation of NSCs into brain endothelial cells by the VEGF signaling and the consequential restoration of the cerebral blood flow would also be one of the therapeutic mechanisms of NSCs. In summary, our data demonstrate that exogenous NSC supplementation could prevent radiation-induced functional loss of the brain. Therefore, successful combination of brain radiation therapy and NSC supplementation would provide a highly promising therapeutic option for patients with various brain diseases.

ObjectiveTremor is a common movement disorder that interferes with daily living. Since the medication for tremor has some limitations, surgical intervention is needed in many patients. In certain patients who cannot undergo aggressive surgical intervention, Gamma Knife thalamotomy (GKT) is a safe and effective alternative.MethodsFrom June 2012 to August 2013, 7 patients with an intractable tremor underwent GKT. Four of these 7 patients had medical comorbidities, and 3 patients refused to undergo traditional surgery. Each patient was evaluated with the modified Fahn-Tolosa-Marin tremor rating scale (TRS) along with analysis of handwriting samples. All of the patients underwent GKT with a maximal dose of 130 Gy to the left ventralis intermedius (VIM) nucleus of the thalamus. Follow-up brain MRI was performed after 3 to 8 months of GKT, and evaluation with the TRS was also performed.ResultsSix patients showed objective improvement in the TRS score. Excluding one patient who demonstrated tremor progression, there was 28.9% improvement in the TRS score. However, five patients showed subjective improvement in their symptoms. On comparing the TRS scores between follow-up periods of more and less than 4 months, the follow-up TRS score at more than 4 months of GKT was significantly improved compared to that at less than 4 months of GKT. Follow-up MRI showed radiosurgical changes in 5 patients.ConclusionGKT with a maximal dose of 130 Gy to the VIM is a safe procedure that can replace other surgical procedures.

Object The goal of this study was to investigate the safety and efficacy of multisession Gamma Knife surgery (GKS) in the treatment of benign orbital tumors. Methods Twenty-three patients who retained their vision despite having tumors touching their optic nerve were treated with multisession (4-fraction) GKS. The median tumor volume was 2800 mm3 (range 211–10,800 mm3), and the median cumulative margin dose was 20 Gy (range 18–22 Gy). Results The median clinical follow-up duration in these patients was 38 months (range 9–74 months). No patient experienced tumor progression in this study. In particular, a higher degree of tumor shrinkage was found in the 7 patients with cavernous hemangiomas than in patients with other types of lesions (p < 0.05). Of the 23 patients whose preoperative vision was preserved, 11 showed improvement in visual acuity and/or visual field and 12 showed stable visual acuity. No GKS-related adverse events were noted during or after treatment. Conclusions Multisession radiosurgery using the Gamma Knife may be a good strategy for tumors in direct contact with the optic nerve. A cumulative margin dose of up to 22 Gy delivered in 4 sessions is safe for preservation of visual function with a high probability of tumor control.