Preclinical Screening for Treatments for Infantile Spasms in the Multiple Hit Rat Model of Infantile Spasms: An Update.

Preclinical Screening for Treatments for Infantile Spasms in the Multiple Hit Rat Model of Infantile Spasms: An Update. Neurochem Res. 2017 May 02;: Authors: Galanopoulou AS, Mowrey WB, Liu W, Li Q, Shandra O, Moshé SL Abstract Infantile spasms are the typical seizures of West syndrome, an infantile epileptic encephalopathy with poor outcomes. There is an increasing need to identify more effective and better tolerated treatments for infantile spasms. We have optimized the rat model of infantile spasms due to structural etiology, the multiple-hit rat model, for therapy discovery. Here, we test three compounds administered after spasms induction in the multiple hit model for efficacy and tolerability. Specifically, postnatal day 3 (PN3) male Sprague-Dawley rats were induced by right intracerebral injections of doxorubicin and lipopolysaccharide. On PN5 p-chlorophenylalanine was given intraperitoneally (i.p.). Daily monitoring of weights and developmental milestones was done and rats were intermittently video monitored. A blinded, randomized, vehicle-controlled study design was followed. The caspase 1 inhibitor VX-765 (50-200 mg/kg i.p.) and the GABAB receptor inhibitor CGP35348 (12.5-100 mg/kg i.p.) each was administered in different cohorts as single intraperitoneal injections on PN4, using a dose- and time-response design with intermittent monitoring till PN5. 17β-estradiol (40 ng/g/day subcutaneously) was given daily between PN...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research