Radiation of the rat brain suppresses seizure-induced neurogenesis and transiently enhances excitability during kindling acquisition

Abstract

Purpose: Adult hippocampal neurogenesis is enhanced in several models for temporal lobe epilepsy (TLE). In this study, we used low-dose whole brain radiation to suppress hippocampal neurogenesis and then studied the effect of this treatment on epileptogenesis in a kindling model for TLE.

Methods: Half of the rats were exposed to a radiation dose of 8 Gy one day before the initiation of a rapid kindling protocol. Afterdischarge threshold (ADT), afterdischarge duration (ADD), clinical seizure severity, and inflammation were compared between groups. On the first and third day after radiation, rats were injected with 5'-bromo-2'-deoxyuridine (BrdU) to evaluate neurogenesis. Seven and 21 days after radiation, numbers of doublecortin (DCX) positive neuroblasts in subgranular zone and granule cell layer were compared between groups.

Results: We showed that radiation significantly suppressed neurogenesis and neuroblast production during kindling acquisition. Radiation prevented an increase in ADT that became significantly lower in radiated rats. On the third and fourth kindling acquisition day radiated rats developed more severe seizures more rapidly, which resulted in a significantly higher mean severity score on these days. Differences in ADD could not be demonstrated.

Discussion: Our results demonstrate that brain radiation with a relatively low dose effectively suppressed the generation of new granule cells and transiently enhanced excitability during kindling acquisition. Although seizure-induced neurogenesis was lower in the radiated rats we could not detect a strong effect on the final establishment of the permanent fully kindled state, which argues against a prominent role of seizure-induced neurogenesis in epileptogenesis.