Rat strain differences in seizure frequency and hilar neuron loss after systemic treatment with pilocarpine

Abstract

At least 3 months after systemic treatment with pilocarpine to induce status epilepticus, Long-Evans and Sprague-Dawley rats were video-EEG monitored for seizures continuously for 1 month. Rats were then perfused, hippocampi were processed for Nissl staining, and hilar neurons were quantified. Seizure frequency in Long-Evans rats was 1/10th of that in Sprague-Dawley rats, and more variable. Hilar neuron loss was also less severe in Long-Evans rats. However, there was no correlation between hilar neuron loss and seizure frequency in either strain. The low and variable seizure frequency suggests limited usefulness of pilocarpine-treated Long-Evans rats for some epilepsy experiments.

Keywords: Epilepsy; Hilus; Long-Evans; Pilocarpine; Seizure; Sprague-Dawley.

Figure 1

Seizures (A) and seizure frequency patterns (B) of pilocarpine-treated Long-Evans (A1, B1) and Sprague-Dawley rats (A2, B2). Some Long-Evans rats had so few seizures that the y-axis scale was magnified for easier visualization (red plots).

Figure 2

Characteristics of seizures in pilocarpine-treated Long-Evans (LE) and Sprague-Dawley rats (SD). Open circles denote females, filled circles designate males. Horizontal lines indicate averages. *P<0.001, Mann-Whitney rank sum test.

Figure 3

Seizure frequency versus time between pilocarpine treatment and onset of seizure monitoring. Regression lines plotted.

Figure 4

Seizure incidence versus time of day of pilocarpine-treated Sprague-Dawley and Long-Evans rats. Lights-on indicated by open bar; lights-off indicated by filled bar. Values represent mean ± s.e.m.

Figure 5

Cumulative seizures versus day for individual pilocarpine-treated Sprague-Dawley (A,B) and Long-Evans rats (C). Regression lines plotted. Rat # indicated in Figure 1.

Figure 6

Hilar neurons in a control Long-Evans rat (A), an epileptic Long-Evans rat (B), and an epileptic Sprague-Dawley rat (C). g = granule cell layer; h = hilus. D Hilar neuron number per hippocampus in epileptic Long-Evans (LE) and Sprague-Dawley rats (SD). Open circles represent females, filled circles represent males. Horizontal lines represent averages. *P=0.042, t test. Control Sprague-Dawley rats are reported to have approximately 44,000 hilar neurons (Buckmaster and Dudek, 1997; Thind et al., 2010), suggesting approximately 63% of hilar neurons died in the epileptic Sprague-Dawley rats of the present study. Control Long-Evans rats had an average of 28,400 hilar neurons, indicating that an average of only 28% had died in epileptic Long-Evans rats.