Background: Cerebellar fastigial nucleus electrical stimulation (FNS) in rats has been shown to protect against brain ischemia/reperfusion (I/R) damage. Activation of telomerase has been reported to provide neuroprotection in animal models of stroke.
Objective: The aim of this study was to explore whether precondition FNS increases the expression of telomerase reverse transcriptase (TERT) and telomerase activity in rats after cerebral I/R injury.
Methods: One day after continuous stimulation of the fastigial cerebellar nucleus for 1 h, adult male Sprague Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h and reperfusion for 24 h, 48 h and 72 h, while the I/R control groups received the same treatment without FNS. Ischemic lesion volumes were measured following TTC staining. The number of apoptotic cells was measured by using TUNEL assays. Subsequently, telomerase activity was examined by using TRAP-silver staining. Additionally, the expression level of TERT mRNA was assessed by using real-time fluorescence quantitative PCR. Finally, the expression of TERT protein was measured by using Western blotting.
Results: The results of our study demonstrated that FNS significantly decreased infarct volumes and improved neurological deficits when compared with the I/R control group. The telomerase activity in the I/R + FNS group was significantly increased compared with that in the I/R control group, particularly in the 24 h reperfusion subgroup (P < 0.05). FNS treatment significantly decreased the number of TUNEL-positive cells when compared with that in the I/R control group. Expression of TERT gradually increased, with the peak occurring after or before 48 h reperfusion and the 24 h and 72 h reperfusion subgroups demonstrating higher expression than each I/R control group (P < 0.05).
Conclusions: Our results show that pre-FNS exerts neuroprotective effects that may be achieved by upregulating the expression of TERT and then by increasing telomerase activity.
Keywords: FNS; I/R; TERT; stroke; telomerase.