Figure 7.

Quantitative analysis of the ratio and density of CB₁-positive excitatory axon terminals in the inner molecular layer of the human dentate gyrus. A, The number of excitatory axon terminals either positive or negative for CB₁ cannabinoid receptor was established using an unbiased stereological estimation method (Geinisman et al., 1996). Altogether, 1092 disector pairs were analyzed, which resulted in 327 terminals in control, 224 terminals in nonsclerotic epileptic, and 197 terminals in sclerotic epileptic patients. The number of CB₁-positive terminals decreased from 235 terminals in control subjects to 106 or 40 terminals in the nonsclerotic or sclerotic epileptic samples, respectively. In contrast, the number of CB₁-negative terminals increased from 92 terminals in control subjects to 118 or 157 terminals in nonsclerotic or sclerotic epileptic samples, respectively. In the quantitative analysis, tissue samples from three individuals from each experimental group were used. B, The ratio of CB₁-positive excitatory axon terminals versus all excitatory axon terminals was 72.8 ± 2.1% in control, 50 ± 2.8% in nonsclerotic epileptic, and 21 ± 3.8% in sclerotic epileptic samples (mean ± SEM). The difference between control and epileptic samples was highly significant (χ² test, ***p < 0.001 both for nonsclerotic and sclerotic epileptic samples). C, The estimated numerical density of CB₁-positive axon terminals in the inner molecular layer of the dentate gyrus of control subjects (0.648 ± 0.075/μm³) was strongly decreased in nonsclerotic epileptic patients (0.3 ± 0.051/μm³) and in sclerotic epileptic patients (0.112 ± 0.021/μm³) as well (values are mean ± SEM). This sharp decline in the density of CB₁-positive axon terminals was statistically significant (ANOVA, p < 0.001). Significance exists between control values and both nonsclerotic and sclerotic epileptic patients (Dunnett's post hoc test, ***p < 0.001). D, The estimated numerical density of CB₁-negative axon terminals was elevated in epileptic samples [density in control samples, 0.248 ± 0.038/μm³; in nonsclerotic samples, 0.326 ± 0.062/μm³; and in sclerotic samples, 0.454 ± 0.07/μm³ (mean ± SEM)]. Increase was significant between analyzed groups (ANOVA, p = 0.04); density of CB₁-negative axon terminals in sclerotic epileptic patients was significantly increased compared with control values (Dunnett's post hoc test, *p = 0.037), but not in nonsclerotic patients (Dunnett's post hoc test, p = 0.546).