Chronic treatment with galantamine rescues reversal learning in an attentional set-shifting test after experimental brain trauma.

Approximately 10 million new cases of traumatic brain injury (TBI) are reported each year worldwide with many of these injuries resulting in higher order cognitive impairments. Galantamine (GAL), an acetylcholine esterase inhibitor (AChEI) and positive allosteric modulator of nicotinic acetylcholine receptors (nAChRs), has been reported to ameliorate cognitive deficits after clinical TBI. Previously, we demonstrated that controlled cortical impact (CCI) injury to rats resulted in significant executive function impairments as measured by the attentional set-shifting test (AST), a complex cognitive task analogous to the Wisconsin Card Sorting Test (WCST). We hypothesized that chronic administration of GAL would normalize performance on the AST post-TBI. Isoflurane-anesthetized adult male rats were subjected to moderate CCI (2.8 mm tissue deformation at 4 m/s) or sham injury. Rats were then randomized into one of three treatment groups (i.e., 1 mg/kg GAL, 2 mg/kg GAL, or 1 mL/kg saline vehicle; VEH) or their respective sham controls. GAL or VEH was administered intraperitoneally daily commencing 24 hours post-surgery and until AST testing at 4 weeks post-injury. The AST data revealed significant impairments in the first reversal stage after TBI, seen as increased trials to reach criterion and elevated total errors (p < 0.05). These behavioral flexibility deficits were equally normalized by the administration of both doses of GAL (p < 0.05). Additionally, the higher dose of GAL (2 mg/kg) also significantly reduced cortical lesion volume compared to TBI + VEH controls (p < 0.05). In summary, daily GAL administration provides an efficacious treatment for cognitive deficits and histological recovery after experimental brain trauma. Clinically, these findings are promising considering robust results were attained using a pharmacotherapy already used in the clinic to treat mild dementia.

Temporal distribution of genetically homogenous 'free-living' Hematodinium sp. in a Delmarva coastal ecosystem.

BACKGROUND: Significant damage to crustacean fisheries worldwide has been associated with Hematodinium sp. It has been postulated that Hematodinium sp. requires passage through the water column and/or intermediate hosts to complete its life cycle. Thus, an understanding of the prevalence and seasonality of Hematodinium sp. within environmentally-derived samples should yield insight into potential modes of disease transmission, and how these relate to infection cycles in hosts. RESULTS: We conducted a two year survey, from 2010-2011, in which 48 of 546 (8.8%) of environmental samples from the Maryland and Virginia coastal bays were positive for Hematodinium sp. between April and November, as based upon endpoint PCR analysis specific to blue crab isolates. Detection in both water and sediment was roughly equivalent, and there were no obvious seasonal patterns. However, there was a high detection in April water samples, which was unanticipated owing to the fact that crabs infected with Hematodinium sp. have not been observed in this early month of the seasonal disease cycle. Focusing on three sites of high prevalence (Sinnickson, VA; Tom's Cove, VA; and Newport Bay, MD) Hematodinium sp. population diversity was analyzed using standard cloning methods. Of 131 clones, 109 (83.2%) were identical, 19 displayed a single nucleotide substitution, and 4 contain two nucleotide substitutions. CONCLUSIONS: Our data suggests a continuous presence of Hematodinium sp. in both water and sediment of a combined Maryland and Virginia coastal bay ecosystem. The detection of Hematodinium sp. in the water column in April is an earlier manifestation of the parasite than predicted, pointing to an as yet unknown stage in its development prior to infection. That the population is relatively homogenous ranging from April to November, at three distinct sites, supports a hypothesis that one species of Hematodinium is responsible for infections within the ecosystem.