Intravitreal injection of bevacizumab was the most effective route of administration for intraocular tissue. Also, bevacizumab injected subconjunctivally was transported into the intraocular tissues of the treated eyes at an effective level. Both intravitreal and subconjunctival injections of bevacizumab resulted in high plasma concentrations. Bevacizumab was distributed into the intraocular tissues in fellow eyes via the systemic circulation. This treatment may be effective for blocking vascular endothelial growth factor activity.

Recent studies demonstrate that rehabilitation ameliorates physical and cognitive impairments of patients with stroke, spinal cord injury, and other neurological diseases and that rehabilitation also has potencies to modulate brain plasticity. Here we examined the effects of compulsive exercise on Parkinson's disease model of rats. Before 6-hydroxydopamine (6-OHDA, 20 microg) lesion into the right striatum of female SD rats, bromodeoxyuridine (BrdU) was injected to label the proliferating cells. Subsequently, at 24 h after the lesion, the rats were forced to run on the treadmill (5 days/week, 30 min/day, 11 m/min). As behavioral evaluations, cylinder test was performed at 1, 2, 3, and 4 weeks and amphetamine-induced rotational test was performed at 2 and 4 weeks with consequent euthanasia for immunohistochemical investigations. The exercise group showed better behavioral recovery in cylinder test and significant decrease in the number of amphetamine-induced rotations, compared to the non-exercise group. Correspondingly, significant preservation of tyrosine hydroxylase (TH)-positive fibers in the striatum and TH-positive neurons in the substantia nigra pars compacta (SNc) was demonstrated, compared to the non-exercise group. Additionally, the number of migrated BrdU- and Doublecortin-positive cells toward the lesioned striatum was increased in the exercise group. Furthermore, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor increased in the striatum by exercise. The results suggest that exercise exerts neuroprotective effects or enhances the neuronal differentiation in Parkinson's disease model of rats with subsequent improvement in deteriorated motor function.

A ten-year follow-up study of stroke among residents 40 years and older in a rural community located on Shikoku Island, Japan, was completed in 1977. The response rate for the initial examinations was 85% of 920 males and 90% of 1,012 females. Seven hundred and seventy-two males and 901 females who were initially free of stroke were followed from July 1967 through June 1977. The incidence of all strokes was 10.47 per thousand person-years for males and 6.41 per thousand person-years for females. The statistically significant risk factors for stroke were age, male sex, elevated blood pressure, ECG abnormalities, and funduscopic abnormalities. Elevated blood pressure was the strongest risk factor and mean arterial pressure was the best predictive measure. Twice as high a proportion of strokes were subclassified as cerebral hemorrhage (26%) in this study as have been reported in comparable studies in the United States (12-15%). An inverse relationship between serum cholesterol levels and cerebral hemorrhage incidence, but not cerebral infarct, was observed. High alcohol intake was a risk factor for cerebral hemorrhage but not for cerebral infarct. No relationship between stroke and weight was observed despite the relationship of stroke to blood pressure and of weight to blood pressure.

These results suggest that electric stimulation prevents apoptosis through the phosphoinositide 3-kinase pathway. Consequently, the ischemic brain might have been rendered as a nurturing microenvironment characterized by robust angiogenesis and diminished microglial/astrocytic proliferation, resulting in the reduction of infarct volumes and behavioral recovery. Electric stimulation is a novel and potent therapeutic tool for cerebral ischemia.

BackgroundMesenchymal stem cells (MSCs) are pluripotent stem cells derived from bone marrow with secretory functions of various neurotrophic factors. Stromal cell-derived factor-1α (SDF-1α) is also reported as one of chemokines released from MSCs. In this research, the therapeutic effects of MSCs through SDF-1α were explored. 6-hydroxydopamine (6-OHDA, 20 μg) was injected into the right striatum of female SD rats with subsequent administration of GFP-labeled MSCs, fibroblasts, (i.v., 1 × 107 cells, respectively) or PBS at 2 hours after 6-OHDA injection. All rats were evaluated behaviorally with cylinder test and amphetamine-induced rotation test for 1 month with consequent euthanasia for immunohistochemical evaluations. Additionally, to explore the underlying mechanisms, neuroprotective effects of SDF-1α were explored using 6-OHDA-exposed PC12 cells by using dopamine (DA) assay and TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining.ResultsRats receiving MSC transplantation significantly ameliorated behaviorally both in cylinder test and amphetamine-induced rotation test compared with the control groups. Correspondingly, rats with MSCs displayed significant preservation in the density of tyrosine hydroxylase (TH)-positive fibers in the striatum and the number of TH-positive neurons in the substantia nigra pars compacta (SNc) compared to that of control rats. In the in vitro study, SDF-1α treatment increased DA release and suppressed cell death induced by 6-OHDA administration compared with the control groups.ConclusionsConsequently, MSC transplantation might exert neuroprotection on 6-OHDA-exposed dopaminergic neurons at least partly through anti-apoptotic effects of SDF-1α. The results demonstrate the potentials of intravenous MSC administration for clinical applications, although further explorations are required.

The number of diabetes mellitus (DM) patients is increasing, and stroke is deeply associated with DM. Recently, neuroprotective effects of glucagon-like peptide-1 (GLP-1) are reported. In this study, we explored whether liraglutide, a GLP-1 analogue exerts therapeutic effects on a rat stroke model. Wistar rats received occlusion of the middle cerebral artery for 90 min. At one hour after reperfusion, liraglutide or saline was administered intraperitoneally. Modified Bederson’s test was performed at 1 and 24 h and, subsequently, rats were euthanized for histological investigation. Peripheral blood was obtained for measurement of blood glucose level and evaluation of oxidative stress. Brain tissues were collected to evaluate the level of vascular endothelial growth factor (VEGF). The behavioral scores of liraglutide-treated rats were significantly better than those of control rats. Infarct volumes of liraglutide-treated rats at were reduced, compared with those of control rats. The level of derivatives of reactive oxygen metabolite was lower in liraglutide-treated rats. VEGF level of liraglutide-treated rats in the cortex, but not in the striatum significantly increased, compared to that of control rats. In conclusion, this is the first study to demonstrate neuroprotective effects of liraglutide on cerebral ischemia through anti-oxidative effects and VEGF upregulation.

BackgroundTo compare peripapillary choroidal thickness measurements between normal and normal-tension glaucoma eyes.MethodsCross-sectional comparative study. 50 normal and 52 normal-tension glaucoma subjects were enrolled in the study. Peripapillary choroidal thickness was measured with spectral-domain optical coherence tomography and enhanced depth imaging. After obtaining circular B-scans around the disc, choroidal thicknesses were calculated based on the exported segmentation values. Visual fields were measured using automated perimetry. Difference in peripapillary choroidal thickness between the normal subjects and the patients with normal-tension glaucoma was analyzed.ResultsThere were no significant differences in age, axial length, or refraction between the two groups. Peripapillary choroidal thickness was inversely correlated with age in both the normal (r = −0.287, P = 0.04) and normal and normal-tension glaucoma (r = −0.322, P = 0.02) groups. Peripapillary choroidal thickness of inferonasal (125 vs 148 μm, P < 0.05), inferior (101 vs 122 μm, P < 0.05), or inferotemporal (100 vs 127 μm, P < 0.05) regions were significantly thinner in the normal-tension glaucoma group as compared to normal subjects. Superior visual hemifield defect was significantly worse than inferior visual hemifield defect in normal and normal-tension glaucoma patients.ConclusionAs compared to normal subjects, peripapillary choroidal thickness was significantly thinner in the normal and normal-tension glaucoma patients, at least in some locations.

GCA thickness measured by Cirrus HD-OCT showed statistically significant structure-function associations with central VF. Inferotemporal central VF had the strongest association.