A healthy blood–brain barrier (BBB) shields the brain from high concentrations of blood glutamate, which can cause neurotoxicity and neurodegeneration. It is believed that traumatic brain injury (TBI) causes long-term BBB disruption, subsequently increasing brain glutamate in the blood, in addition to increased glutamate resulting from the neuronal injury. Here, we investigate the relationship between blood and brain glutamate levels in the context of BBB permeability. Rats exposed to BBB disruption through an osmotic model or TBI and treated with intravenous glutamate or saline were compared to control rats with an intact BBB treated with intravenous glutamate or saline. After BBB disruption and glutamate administration, the concentrations of glutamate in the cerebrospinal fluid and blood and brain tissue were analyzed. The results showed a strong correlation between the brain and blood glutamate concentrations in the groups with BBB disruption. We conclude that a healthy BBB protects the brain from high levels of blood glutamate, and the permeability of the BBB is a vital component in regulating levels of glutamate in the brain. These findings bring a new approach to treating the consequences of TBI and other diseases where long-term disruption of the BBB is the central mechanism of their development.
1 February 2016 in Canadian Journal of Ophthalmology
Purpose: We recently showed the positive clinical effects of combining accelerated corneal cross-linking (PACK-CXL) with antibiotic treatment in patients with presumed bacterial keratitis. In this study, we compare the impacts of a combined PACK-CXL/standard antibiotic treatment (PACK-ABX group) with standard antibiotic treatment alone (ABX group) in patients with culture-confirmed bacterial keratitis. Methods: We reviewed patients with moderate and severe bacterial keratitis and confirmed bacterial cultures. Clinical outcomes were compared for standard antibiotic treatment alone, before the initiation of PACK-CXL, and after adjuvant use of PACK-CXL. Results: A total of 47 eyes of 47 patients were included: 26 eyes in the PACK-ABX group and 21 eyes in the ABX group. Pathogens, baseline demographics (besides age), and clinical parameters were similar between the 2 groups. The PACK-ABX patients had better final uncorrected visual acuity [mean difference 0.57 Logarithm of the Minimum Angle of Resolution, 95% Confidence Interval (CI): 0.16–0.99, P = 0.07] and best-corrected visual acuity (mean difference 0.70 Logarithm of the Minimum Angle of Resolution, 95% CI: 0.23–1.16, P = 0.04), shorter reepithelialization time (mean difference 9.63 days, 95% CI: 3.14–16.12, P = 0.004), and reduced number of clinic visits (mean difference 4.8 meetings, 95% CI: 1.4–8.2, P = 0.007) and need for tectonic grafts (0 vs. 33.3%, P = 0.002). A multivariate analysis controlling for age, sex, ulcer size, and Gram stain showed that PACK-ABX treatment remained significantly associated with reepithelialization time (β = 14.5, P = 0.001). Conclusions: In our study, PACK-CXLs addition to the standard of care in cases of culture-proven bacterial keratitis had a positive effect on the final visual acuity and time to resolution, compared with the standard-of-care treatment.
Advancements in surgical techniques and increased life expectancy have made cataract surgery more common among very old patients. However, surgical outcomes seem impaired in patients older than 90 years, especially with ocular comorbidities. A retrospective case-control study of 53 eyes of 53 very old patients (mean 92.6 ± 3.0) and 140 eyes of 140 matched patients (mean 75.2 ± 7.6) was undertaken. Groups were matched in terms of gender and systemic and ocular comorbidities. In very old patients, higher phacoemulsification energy (cumulative dissipated energy [CDE], 25.0 ± 22.4 vs. 16.1 ± 10.7, p = 0.01) and rate of intraoperative floppy iris syndrome (IFIS, 9.4% vs. 1.4%, p = 0.02) were observed compared to controls. Uncorrected (UCVA) and best-corrected distance visual acuity (BCVA) gains were significantly poorer among the very old patients than among the control at postoperative day 30 (0.20 ± 0.70 vs. 0.56 ± 0.61 logMAR, p < 0.001 and 0.27 ± 0.64 vs. 0.55 ± 0.62 logMAR, p = 0.006, respectively). Even after including CDE and IFIS as covariates, age remained an independent factor for poor visual gain at 30 days (p < 0.001). Cataract surgery in very old patients may demand more experienced surgeons due to higher nuclear density and the rates of IFIS. Expectations in visual acuity gains should be aligned with the patient’s age.