Effects of Acrylic Tunnel Enrichment on Anxiety-Like Behavior, Neurogenesis, and Physiology of C57BL/6J Mice.

Environmental enrichment for mice lags behind the standard enrichment offered to other laboratory rodents due to concerns about environmental variability and, in specific contexts, aggression. Our objective in this study was to evaluate concerns that the introduction of structural enrichment in the form of a single red acrylic mouse tunnel into murine housing may confound study findings. We measured effects on anxiety-like behaviors (elevated zero maze and open field activity), hippocampal neurogenesis, body weight gain, and physiologic markers of stress (adrenal gland weight, plasma corticosterone concentration, and neutrophil:lymphocyte ratio). Male and female C57BL/6J mice were randomly assigned to one of 2 groups: a standard-housed control group with enrichment consisting of paper nesting material, or an enriched group that received a single acrylic tunnel in addition to nesting material. All results fell within biologically normal ranges regardless of treatment, and variability (standard deviation) was not significantly different between groups for any measure. Mice in the enriched group showed modest differences during open field testing suggestive of decreased anxiety, traveling farther and depositing fewer fecal boli than standard-housed mice. Male mice in the tunnel-enriched group gained more body weight than standard-housed male mice. No significant effects by treatment were found in neurogenic or physiologic parameters. These results indicate that provision of simple structural enrichment is unlikely to have confounding effects on murine anxiety-like behaviors, neurogenesis, body weight gain, or physiologic parameters. We therefore recommend the inclusion of simple structural enrichment, such as an acrylic tunnel, to the standard environmental enrichment of social housing and nesting material for mice.

Severe Periocular Edema after Intraarterial Carboplatin Chemotherapy for Retinoblastoma in a Rabbit (Oryctolagus cuniculus) Model.

Endovascular microcatheter-based intraarterial (ophthalmic artery) chemotherapy is becoming widely used for the clinical treatment of intraocular retinoblastoma due to its apparent increased efficacy compared with traditional intravenous chemotherapy; however local ocular complications are not uncommon. Carboplatin is a chemotherapeutic agent used in both intravenous and intraarterial chemotherapy. We used rabbits to assess pharmacokinetics and ocular and systemic toxicity after intraarterial carboplatin infusion. Subsequent to unilateral intraarterial administration of carboplatin, severe unilateral or bilateral periocular edema occurred in 6 adult male New Zealand white rabbits. Time to onset varied from less than 4 h after administration (n = 3, 50 mg) to approximately 24 h afterward (n = 3, 25 mg). After becoming symptomatic, 5 of the 6 animals were promptly euthanized, and the remaining animal (25 mg treatment) was medically managed for 4 d before being euthanized due to intractable edema-related lagophthalmos. Globes and orbits from all 6 euthanized rabbits were harvested en bloc; whole-mount sections were prepared for histologic evaluation, which revealed drug-induced vasogenic edema in confined spaces as the main underlying pathogenesis. Transient and self-limiting periocular edema is a common side effect of intraarterial chemotherapy but is thought to occur predominantly with melphalan monotherapy or combination therapy using melphalan, carboplatin, and topotecan. The severity of this adverse consequence in rabbits was unexpected, and its use in the study was subsequently discontinued. Although the definitive cause for this vasotoxicity and striking clinical presentation is unknown, we suspect species-specific anatomic features and sensitivity might have contributed to amplified complications after intraarterial carboplatin chemotherapy of the eye. Due to the adverse effects of intraarterial carboplatin chemotherapy that we observed in 2 experimental cohorts of rabbits, we recommend caution regarding its use in this species.