Neural stem and progenitor cells support and protect adult hippocampal function via vascular endothelial growth factor secretion.

Adult neural stem and progenitor cells (NSPCs) reside in the dentate gyrus (DG) of the hippocampus throughout the lifespan of most mammalian species. In addition to generating new neurons, NSPCs may alter their niche via secretion of growth factors and cytokines. We recently showed that adult DG NSPCs secrete vascular endothelial growth factor (VEGF), which is critical for maintaining adult neurogenesis. Here, we asked whether NSPC-derived VEGF alters hippocampal function independent of adult neurogenesis. We found that loss of NSPC-derived VEGF acutely impaired hippocampal memory, caused neuronal hyperexcitability and exacerbated excitotoxic injury. We also found that NSPCs generate substantial proportions of total DG VEGF and VEGF disperses broadly throughout the DG, both of which help explain how this anatomically-restricted cell population could modulate function broadly. These findings suggest that NSPCs actively support and protect DG function via secreted VEGF, thereby providing a non-neurogenic functional dimension to endogenous NSPCs.

The effect of IV ketamine in patients with major depressive disorder and elevated features of borderline personality disorder.

BACKGROUND: Comorbid borderline personality disorder and major depressive disorder is common and often not adequately responsive to standard antidepressant therapies. Ketamine is a potentially life-saving option. METHODS: 153 adult patients with MDD were assessed with the Personality Assessment Inventory (PAI) Borderline Subscale. Data was normally distributed with a mean + SD of 38.95 + 11.54. Patients >1 SD above the mean were assigned to the MDD + BF group. All others were assigned to the MDD-BF group. Patients were administered IV ketamine 0.5 mg/kg of ketamine over 40 min. Mood was assessed using the Beck Depression Inventory-II at baseline, 3 and 24 h post-ketamine. Scores between the MDD + BF and MDD-BF group at each time point were compared using t-test or analysis of covariance (ANCOVA) model. The primary outcome was response at 24 h. RESULTS: The LS mean change in BDI at 24 h was -23.8 (15.3) for MDD + BF and -21.0 (13.5) for MDD-BF (F [1151] = 0.043, p = 0.51). The LS mean change in BDI at 3 h was -21.3 (13.2) for MDD + BF and -19.6 (13.2) for MDD-BF (F[1151] = 0.045, p = 0.83). The LS mean change in BDI at 14 days was -23.2 (15.3) for MDD + BF and -15.3 (15.2) for MDD-BF (F[1130] = 4.24, p = 0.04). LIMITATIONS: People in the MDD + BF group were not necessarily diagnosable with borderline personality disorder. CONCLUSIONS: These data indicate that IV ketamine is effective in MDD patients with and without elevated borderline features. This can provide clinicians some reassurance about using ketamine in this population.

Real-World Outcomes in Patients with Branch Retinal Vein Occlusion- (BRVO-) Related Macular Edema Treated with Anti-VEGF Injections Alone versus Anti-VEGF Injections Combined with Focal Laser.

The purpose of this study was to assess outcomes in a real-world nonclinical trial setting of antivascular endothelial growth factor (VEGF) injections alone vs. focal laser combined with anti-VEGF injections in patients with branch retinal vein occlusion- (BRVO-) related macular edema (ME). This study included 88 BRVO with ME patients who were treated over three years at both a tertiary referral center in the Birmingham metropolitan area and satellites in rural Alabama. One group received only anti-VEGF injections (n = 56); the other group received both anti-VEGF injections and focal laser (n = 32). The following outcome measures were evaluated: initial and final visual acuities (VA), initial central subfield thickness (CST) on OCT, number of injections, number of lasers, percentage of patients with a gain of 3 lines of VA, percentage of patients with VA better than or equal to 20/40, and percentage of patients with VA worse than or equal to 20/200. We found that there was no difference in initial VA (p=0.913) or CST (p=0.961) between the two groups. The injection only group required a median of 7 injections, while the combination group required a median of 4 injections, but this was not a statistically significant difference (p=0.117). There was no difference in final VA (p=0.414) or any of the other visual outcomes between the two groups. In conclusion, focal laser did not decrease the number of injections required or improve the VA in BRVO-related ME. Although visual outcomes were similar in both groups, focal laser does not appear to be of additional benefit in BRVO-related ME in the anti-VEGF era.

Functional assessment of glaucoma: Uncovering progression.

Clinicians who manage glaucoma patients carefully monitor the visual field to determine if treatments are effective or interventions are needed. Visual field tests may reflect disease progression or variability among examinations. We describe the approaches and perimetric tests used to evaluate glaucomatous visual field progression and factors that are important for identifying progression. These include stimulus size, which area of the visual field to assess (central versus peripheral), and the testing frequency, evaluating which is important to detect change early while minimizing patient testing burden. We also review the different statistical methods developed to identify change. These include trend- and event-based analyses, parametric and nonparametric tests, population-based versus individualized approaches, as well as pointwise and global analyses. We hope this information will prove useful and important to enhance the management of glaucoma patients. Overall, analysis procedures based on series of at least 5 to 6 examinations that require confirmation and persistence of changes, that are guided by the pattern and shape of the glaucomatous visual field deficits, and that are consistent with structural defects provide the best clinical performance.

A Larger Social Network Enhances Novel Object Location Memory and Reduces Hippocampal Microgliosis in Aged Mice.

The mammalian hippocampus shows marked decline in function with aging across many species, including humans and laboratory rodent models. This decline frequently manifests in memory impairments that occur even in the absence of dementia pathology. In humans, a number of factors correlate with preserved hippocampal memory in aging, such as exercise, cognitive stimulation and number of social ties. While interventional studies and animal models clearly indicate that exercise and cognitive stimulation lead to hippocampal preservation, there is relatively little research on whether a decline in social ties leads to cognitive decline or vice versa. Even in animal studies of environmental enrichment in aging, the focus typically falls on physical enrichment such as a rotating cast of toys, rather than the role of social interactions. The present studies investigated the hypothesis that a greater number of social ties in aging mice would lead to improved hippocampal function. Aged, female C57/Bl6 mice were housed for 3 months in pairs or large groups (7 mice per cage). Group-housed mice showed greater novel object location memory and stronger preference for a spatial navigation strategy in the Barnes maze, though no difference in escape latency, compared to pair-housed mice. Group-housed mice did not differ from pair-housed mice in basal corticosterone levels or adult hippocampal neurogenesis. Group-housed mice did, however, show reduced numbers of Iba1/CD68+ microglia in the hippocampus. These findings suggest that group housing led to better memory function and reduced markers of neuroinflammation in aged mice. More broadly, they support a causative link between social ties and hippocampal function, suggesting that merely having a larger social network can positively influence the aging brain. Future research should address the molecular mechanisms by which a greater number of social ties alters hippocampal function.