Neuroprotective Effect of Eliprodil: Attenuation of a Conditioned Freezing Deficit Induced by Traumatic Injury of the Right Parietal Cortex in the Rat

Abstract

We have previously demonstrated that a lateral fluid percussion-induced traumatic lesion of the right parietal cortex can lead to a deficit in a conditioned freezing response and that this deficit can be attenuated by both pre- and postlesion administration of the NMDA receptor antagonist dizocilpine. In the present study, we investigated the effects of eliprodil, a noncompetitive NMDA receptor antagonist acting at the polyamine modulatory site, which also acts as a Ca2+ channel blocker, on the trauma-induced conditioned freezing deficit. Eliprodil produced a 50% reduction in this deficit when administered as three 1 mg/kg injections i.v. at 15 min, 6 h, and 24 h following the lesion. Approximately the same degree of protection was afforded when 2 x 1.5 mg/kg were administered 6 and 24 h and equally at 12 and 24 h after surgery (56% and 59%, respectively). A single treatment (3 mg/kg) at 24 h was ineffective against the deficit. The protection afforded with treatment at 6 and 24 h after lesion was dose dependent, with a minimal active dose of 2 x 0.75 mg/kg. These data complement those previously published on the ability of eliprodil to reduce lesion volume following traumatic brain injury and show, in addition, that the neuroprotective effect has functional consequences.

Evaluation of11C-Me-NB1 as a Potential PET Radioligand for Measuring GluN2B-Containing NMDA Receptors, Drug Occupancy, and Receptor Cross Talk

“…In preclinical studies, eliprodil had neuroprotective effects at 1 mg/kg (4,40,41). This corresponds to full ($99.5%) receptor occupancy in our study.…”

Sex differences in cued fear responses and parvalbumin cell density in the hippocampus following repetitive concussive brain injuries in C57BL/6J mice

“…Finally, the perilesional/parietal cortex damage, evident by astrogliosis, could have led to deficits in contextual encoding during the association trial. As discussed by Hogg and colleagues [65], damage to the parietal cortex can cause many functional deficits (e.g., spatial localization deficits [66], spatial neglect [67]) that may lead to a failure to properly encode the features of the environment. In addition, the parietal cortex contains neurons that respond to a single modality or are multimodal, responding to any single modality (e.g., visual, tactile), or combination of, sensory modalities [68].…”

Animal models of post-traumatic epilepsy and their neurobehavioral comorbidities

“…Additionally, tests of working memory have demonstrated injury-induced cognitive deficits [56,60]. Deficient conditioning in the Perspex box test, which evaluates conditioned freezing, is observed after mild traumatic lesion [61,62]. Furthermore, LFPI induces acute increases in the stress response as measured by serum hormone levels [53,63,64].…”