Cumulative Effects of Repeated Low-Level Blast on the Optic Nerve in a Rat Model

Abstract

Purpose: Visual dysfunction is a common symptom observed in victims of blast-induced traumatic brain injury (TBI). While effects on the brain of primary blast exposure have been extensively studied, less is known about primary blast effects on the eye or visual system. In particular, little is known about the cumulative effects of repeated low-level blast exposure. The purpose of this study is to characterize the effects of repeated low-level blast exposure on the optic nerve using a rat model.

Methods: A compressed-air driven shock tube was used to expose Long-Evans rats to blast waves of peak overpressure 68 ± 3 kPa and positive peak duration 2.8 ± 0.1 msec. Rats were divided into groups receiving either a single blast exposure (SBE), SBE after 1hr (SBE+1hr), repeated blast exposure (RBE), control groups (CTR) or CTR with repeated sedations (CTRS). Optic nerves were collected at indicated sampling time points then processed for immunohistochemistry to detect activated caspase 3, ionized calcium-binding adapter molecule 1 (iba-1) and glial fibrillary acidic protein (GFAP).

Results: Activated caspase 3 was detected in the optic nerves from RBE and SBE rats, but not in SBE+1hr, CTR and CTRs rats. A significantly higher number of activated caspase 3 positive cells were found in the portions of the optic nerve closest to the eye and optic chiasm in RBE rats than in SBE rats. Activated microglial cells were detected by iba-1 in the optic nerve of all groups. A significantly higher number of iba-1 positive cells were found in the optic nerves of RBE rats. GFAP expression was observed in the optic nerve of all groups. However, a higher level of GFAP was observed in the RBE rats.

Conclusions: Low-level repeated blast exposure lead to an increase in apoptosis in the optic nerve as indicated by increased caspase 3 positive cells. Sections of the optic nerve closest to the eye and brain were more susceptible. RBE increased gliosis and activated microglia at the optic nerve . This suggests that there is either a cumulative effect or a delay in healing from repeated low-level blast exposure that may lead to visual dysfunction.