The effects of voluntary running on cerebrovascular morphology and spatial short-term memory in a mouse model of amyloidosis.

Physical activity has been correlated with a reduced risk of cognitive decline, including that associated with vascular dementia, mild cognitive impairment (MCI) and Alzheimer's disease (AD); recent literature suggests this may in part result from benefits to the cerebrovascular network. Using a transgenic (Tg) mouse model of AD, we evaluated the effect of running on cortical and hippocampal vascular morphology, cerebral amyloid angiopathy, amyloid plaque load, and spatial memory. TgCRND8 mice present with progressive amyloid pathology, advancing from the cortex to the hippocampus in a time-dependent manner. We postulated that the characteristic progression of pathology could lead to differential, time-dependent effects of physical activity on vascular morphology in these brain regions at 6 months of age. We used two-photon fluorescent microscopy and 3D vessel tracking to characterize vascular and amyloid pathology in sedentary TgCRND8 mice compared those who have a history of physical activity (unlimited access to a running wheel, from 3 to 6 months of age). In sedentary TgCRND8 mice, capillary density was found to be lower in the cortex and higher in the hippocampus compared to non-transgenic (nonTg) littermates. Capillary length, vessel branching, and non-capillary vessel tortuosity were also higher in the hippocampus of sedentary TgCRND8 compared to nonTg mice. Three months of voluntary running resulted in normalizing cortical and hippocampal microvascular morphology, with no significant difference between TgCRND8 and nonTg mice. The benefits of physical activity on cortical and hippocampal vasculature in 6-month old TgCRND8 mice were not paralleled by significant changes on parenchymal and cerebral amyloid pathology. Short-term spatial memory- as evaluated by performance in the Y-maze- was significantly improved in running compared to sedentary TgCRND8 mice. These results suggest that long-term voluntary running contributes to the maintenance of vascular morphology and spatial memory in TgCRND8 mice, even in the absence of an effect on amyloid pathology.

Growth-Friendly Surgery Is Effective at Treating Early-Onset Scoliosis Associated With Goldenhar Syndrome.

OBJECTIVE: To evaluate the radiographic results and complications of growth-friendly (GF) surgery in the treatment of early-onset scoliosis (EOS) associated with Goldenhar syndrome. BACKGROUND: Goldenhar syndrome has been associated with spinal deformity, which may be progressive. Efficacy and complication rate of GF treatment has not been reported for this population of patients with EOS. METHODS: Patients with Goldenhar syndrome and EOS with two years' follow-up were identified from two international multicenter EOS databases. Scoliosis, kyphosis, spine height, and hemithoracic height/width were determined preimplant, immediately postoperative, and at the two-year follow-up. Severity of complications (SV) was recorded (Smith et al. JPO 2015). RESULTS: Ten patients met inclusion criteria and had a mean age of 4.6 ± 2.5 years at GF implantation (one spine and nine rib-based). Mean preoperative scoliosis was 64°, postimplant 52°, and at mean follow up of 2.4 ± 0.5 years was 50° (p = .09). Preoperative kyphosis was 36°, postimplant 38°, and final 42° (p = .08). Preoperative T1-S1 height was 23.5 cm, postimplant 23.6 cm, and final 27.3 cm (p = .06). Preoperative convex hemithoracic height was 10.4 cm, postimplant 7.9 cm, and final 12.8 cm (p < .05). Preoperative concave hemithoracic height was 8.4 cm, postimplant 8.8 cm, and final 9.9 cm (p = .30). Preoperative right hemithoracic width was 8.02 cm, postimplant 7.22 cm, and final 7.86 cm (p = .07). Preoperative left hemithoracic width was 7.18 cm, postimplant 7.86 cm, and final 8.60 cm (p = .43). Eight patients had ≥1 complication with SV I (n = 7), SV II (n = 2), and SV IIA (n = 7). These included infection (n = 4), migration (n = 3), pneumonia (n = 2), and instrumentation failure (n = 2). CONCLUSION: At minimum two-year follow-up, GF surgical intervention for the treatment of EOS associated with Goldenhar syndrome trended toward improvements in scoliosis and spine height, but had a significant improvement in convex hemithoracic height; however, the majority of patients experienced severity grade I or II complications. LEVEL OF EVIDENCE: Level IV.